bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogenous Regulation of Rat Brain Mast Cell Serotonin Release
Authors: Marathias Katerina , Lambracht-Hall Mona , Savala John , Theoharides Theoharis C.
Published: August 2009

Mast cells are involved in allergic reactions where they release numerous vasoactive and other mediators in response to IgE and antigen. They are also activated by neuropeptides and are found in close contact with neurons. Mast cell heterogeneity has now been documented for mucosal mast cells and connective tissue mast cells. Rat brain mast cells were studied in a perfusion system and were shown to release serotonin in response to the mast cell secretagogue compound 48/80 (C48/80). High-potassium neuronal depolarization also released serotonin, but this was calcium dependent, not associated with β-hexosaminidase, and was unaffected by prior treatment with C48/80. Neuronal depolarization, however, was associated with somatostatin secretion and substantially reduced subsequent C48/80 stimulation, an effect abolished by neonatal treatment of the animals with capsaicin. Perfusion with somatostatin and substance P also induced brain mast cell serotonin release. C48/80 stimulation of combined thalamic and hypothalamic slices after neuronal depolarization substantially reduced the C48/80 effect, suggesting the possible presence of endogenous inhibitors released from the hypothalamus. Finally, the α2-receptor agonist clonidine had a slight stimulatory effect. These results indicate that brain mast cell serotonin release may be regulated by endogenous neurotransmitters and/or neuro-modulators.
Distribution and Engraftment Patterns of Human Tonsillar Mononuclear Cells and Immunoglobulin-Secreting Cells in Mice with Severe Combined Immunodeficiency: Role of the Epstein-Barr Virus
Authors: Nadal David , Albini Boris , Chen Chaoyuan , Schläpfer Erika , Bernstein Joel M. , Ogra Pearay L.O.
Published: August 2009

Tonsils seem to be the ideal source for lymphocytes seeding to the mucosa of the respiratory tract. The distribution and engraftment of human lymphocytes injected into mice with severe combined immunodeficiency (SCID) are not well understood. C.B-17 SCID mice were injected intraperitoneally with human tonsillar mononuclear cells (hu-TMC). The hu-TMC-SCID mouse chimeras were subsequently tested for the appearance and distribution of human lymphocytes tagged with H33342 and immunoglobulin-secreting cells in various systemic and mucosal immunocompetent tissues. This was done by fluorescence microscopy of tissue sections for cells supravitally stained before transfer and by an enzyme-linked immunospot assay using cells isolated from murine organs. Most importantly, engraftment of hu-TMC proved to be dependent on the presence of anti-Epstein-Barr virus (EBV) antibody in the donor. hu-TMC engrafted, in decreasing numbers, in the following systemic organs: peritoneal cavity, liver, spleen and bone marrow. Among mucosal tissues tested, hu-TMC were seen in lungs, but not in the intestines. The engraftment of hu-TMC in the lung was more extensive than that in the spleen. These studies demonstrate that hu-TMC engraft in a variety of murine tissues. The striking preference of hu-TMC for the lungs when compared to intestines suggests selective engraftment among distinct mucosal tissues. The hu-TMC-SCID mouse chimera promises to be a unique animal model to study human-mucosa-associated lymphoid cells and EBV-related lymphomagenesis and B cell tumor progression.
Effects of the Platelet-Activating Factor Antagonist BN 52021 on Anti-Islet Cytotoxicity of Mononuclear Cells and Serum from Type 1 (Insulin-Dependent) Diabetic Patients
Authors: Köhler E. , Varnai G. , Knospe S. , Förster W. , Michaelis D. , Wanka H.
Published: August 2009

The effect of platelet-activating factor (PAF) antagonist BN 52021 (0.06–2.5 mM) on the cytotoxic activity of mononuclear cells (MNC) from newly diagnosed type 1 diabetic patients against 51Cr-labeled Langerhans islets from neonatal rats was investigated in a 6-hour cytotoxicity test. A dose-dependent inhibition of anti-islet cytotoxicity by BN 52021 was observed. The suppression of the islet lysis was significant at a concentration of 0.6 mM BN 52021. During a 4-day cell culture, BN 52021 had no inhibitory effect on the antigen-mediated triggering of immunocytes with anti-islet cytotoxicity. The results suggest that the drug is only effective during immunocytolytic reactions of MNC against pancreatic islets. A PAF-independent action of BN 52021 can not be excluded at present.
IL-4-Producing Murine T Helper Cell Line Provides Help for in vitro Production of IgE
Authors: Poulsen L.K. , Katamura K. , Ishizaka K.
Published: August 2009

Studies of the regulation of the IgE synthesis have been hampered by the difficulties in making lymphocytes produce IgE in vitro. Synthesis of IgE, IgG1 and IgM were investigated in a murine coculture system in which a conalbumin-specific T helper cell line of Th2 type was cultured together with nonadherent splenocytes from normal MHC-matched mice. Help provided by the antigen-stimulated T cell line induced significant IgE production (20 ng/ml), along with IgG1 (5 μg/ml) and IgM (250 μg/ml). Immunoglobulin synthesis in cultures was detectable at day 3–4 and culminated at day 7–8. IL-4 production was observed within the first 2 days of culture. The kinetics of the synthesis of the three isotypes were parallel. Stimulation of the Th2 cell line with Con A produced dose-response curves resembling those after antigen stimulation, whereas supernatant from these cells was unable to induce synthesis of IgE. The presence of interferon-γ in the cultures, inhibited synthesis of IgE, IgM and IgG1, but this inhibition was not due to interference with the IL-4 production, which increased in the presence of high doses of interferon-γ.
Tumor Necrosis Factor Production by Human Granulocytes
Authors: Mándi Y. , Endrész V. , Krenács L. , Régely K. , Degré M. , Béládi I.
Published: August 2009

Human polymorphonuclear leukocytes kill WEHI 164 cells in an 18-hour 51Cr release assay. Antibody to human tumor necrosis factor (TNF) blocks the lysis of targets mediated by human granulocytes. Resting granulocytes produce an undetectable amount of TNF, if any. Granulocytes stimulated with Staphylococcus aureus release 250–500 U/ml TNFα. The specificity of the released TNF in the WEHI 164 cytotoxicity assay was confirmed by using neutralizing anti-TNFα monoclonal antibodies. The thymidine uptake of endothelial cells was inhibited by granulocyte-derived TNF. The identity of TNFα was further confirmed by molecular weight determination, by gel filtration on Sephacryl S-200, with a result of approximately 44,000. Besides their antimicrobial capacity, therefore, granulocytes may contribute to tumor rejection, inflammation and septic infections by releasing TNF.
Induction of Auto-Antibody Formation in C3H/HeJ Mice by Cobra Venom Factor
Authors: Bloembergen Peter , Hol Cees , Hofhuis Frans M.A. , van Dijk Hans
Published: August 2009

Recently, we demonstrated that lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice show a very high background number of splenic antibody-forming cells with specificity for bromelain-treated isologous erythrocytes. This background level was not or only slightly enhanced by LPS injection. In this paper it is reported that the existing response of C3H/HeJ mice is about doubled by treatment of the animals with cobra venom factor (CVF). This increase is very similar to the LPS-induced potentiation of the auto-antibody response of C3H/Tif and other LPS-responder mice. The absence of auto-antibodies in the sera of CVF-treated C3H/HeJ mice, however, points at a different mechanism of B cell activation. The mediation of the CVF-induced stimulation of the B cells of C3H/HeJ mice by covalent C3-glycoprotein complexes and the need for an additional stimulus is discussed.
Effects of Antiasthma Drugs on Superoxide Anion Generation from Human Polymorphonuclear Leukocytes or Hypoxanthine-Xanthine Oxidase System
Authors: Kato Masahiko , Morikawa Akihiro , Kimura Hirokazu , Shimizu Toshio , Nakano Minoru , Kuroume Takayoshi
Published: August 2009

Airway inflammation with human polymorphonuclear leukocytes (PMNs) may play an important role in the pathophysiology of bronchial asthma. Superoxide anion (O2––) and other active oxygen species derived from PMNs cause tissue damage. To evaluate the effects of antiasthma drugs on airway inflammation or antioxidative actions due to the inhibition of O2–– generation, we investigated the effects of antiallergic drugs, β-adrenergic agonists, theophylline and corticosteroids, on the in vitro generation of O2–– by human PMNs, using a chemiluminescence (CL) method dependent on a Cypridina luciferin analog (MCLA), a highly sensitive and specific CL probe for O2––. We found that azelastine, one of the antiallergic drugs, and isoproterenol inhibited FMLP-induced O2–– generation in a dose-dependent fashion, whereas the other drugs exhibited no such inhibitory action except at very high concentrations. Furthermore, we found that isoproterenol inhibited O2 generation from the hypoxanthine-xanthine oxidase system (an O2––-generating system) in a dose-dependent fashion, unlike azelastine and the other drugs. These results suggest that azelastine and isoproterenol inhibit the process of O2–– generation from PMNs, while isoproterenol also scavenges O2––. These drugs may be beneficial in the treatment of airway inflammation due to O2–– generation in bronchial asthma.
Delayed-Type Hypersensitivity Antigens Detected in Culture Supernatants of Salmonellatyphimurium
Authors: Cho N. , Shinomiya H. , Matsumura H. , Wang F.Z. , Nakano M.
Published: August 2009

Protein antigens eliciting delayed type hypersensitivity (DTH) were analyzed and purified from the supernatants of protein-free cultures in which Salmonella typhimurium TV148 organisms had grown. DTH activity was measured by the footpad swelling test in mice immunized with living organisms of S. typhimurium TV148 or Escherichia coli K-12. DTH activity in the culture supernatant was specific to TV148-immunized mice. This activity was destroyed by pronase. DTH activity was unable to pass through an ultrafilter with an exclusion limit of 10 kD. After condensation of the supernatant and following centrifugation (100,000 g for 1 h), the DTH activities of the sediment and the supernatant were examined, and both showed DTH activity. Further analyses of DTH antigens in the supernatant by HPLC gel filtration separated the activity into three portions. The most active portion was further fractionated by hydroxyapatite HPLC, revealing the presence of two DTH antigens, with molecular weights of 65 and < 10 kD. These results indicate that the culture supernatant of S. typhimurium TV148 organisms contains a variety of macromolecular protein DTH-eliciting antigens, and one of the antigens is 65 kD, which is dissociated partly by organic solvents into a low molecular weight (< 10 kD) antigen.
Mast Cell Hyperplasia in Experimental Hypersensitivity Pneumonitis
Authors: Haley Patrick J. , Schuyler Mark , Gott Katherine , Casale Thomas B.
Published: August 2009

We investigated the presence of mast cells in a model of experimental hypersensitivity pneumonitis (EPH). Guinea pigs exposed to 8 weekly intratracheal challenges with Micropolyspora faeni exhibited significant increases in the number of mast cells within the lung as compared to controls and animals challenged only 2 or 4 times. The number of cells in M. faeni-challenged animals were increased around bronchi, bronchioles, blood vessels and in alveolar septa. There appeared to be contraction of peribronchial, peribronchiolar and vascular smooth muscle. Ultrastructural examination of lung tissue revealed the presence of degranulating mast cells. Bronchoalveolar lavage histamine levels were increased after 8 but not after 2 or 4 weekly challenges. Serum anti-M faeni antibody was present in all M. faeni-exposed animals but not in control animals. We conclude that mast cells and histamine levels in bronchoalveolar lavage fluid are increased in a model of EHP caused by repetitive, intratracheal injection of M. faeni particulate antigen.
Serum Eosinophil Cationic Protein in Patients with Atopic Dermatitis
Authors: Paganelli R. , Fanales-Belasio E. , Carmini D. , Scala E. , Meglio P. , Businco L. , Aiuti F.
Published: August 2009

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin, frequently associated with a family history of atopy, raised serum IgE levels and other immunological abnormalities. Both eosinophils and their basic proteins have been detected in the skin lesions of AD patients. We measured the levels of eosinophil cationic protein (ECP) in sera of 24 children with AD and found them to be increased, compared to nonatopic controls, both children and adults. High ECP values were also obtained in 3 patients with the hyper-IgE syndrome. However, no direct relationship between IgE and ECP serum levels could be established. We found no correlation between serum ECP and the number of circulating eosinophils, suggesting that part of ECP was produced by cells infiltrating the tissues. Measurement of ECP might represent a noninvasive tool to assess the activity of AD in relation to eosinophil involvement in this disease.
Characteristics of Histamine Secretion from Mast Cells Stimulated with Sodium Orthovanadate and Other Vanadium Compounds
Authors: Al-Laith Mariam , Pearce F.L.
Published: August 2009

Sodium orthovanadate was found to be an effective histamine liberator from serosal mast cells of the rat and mouse. The release process was slow, non-cytotoxic and strongly dependent on pH and extracellular calcium. The effect was highly tissue and species specific and human basophil leucocytes, human lung mast cells and tissue mast cells of the rat and guinea pig were only weakly responsive or essentially unreactive. Other oxyanions of vanadium with the metal in the (+V) oxidation state also evoked histamine release from rat peritoneal mast cells but neither vanadyl sulphate (+IV oxidation state) nor the analogous orthophosphate anion were effective secretagogues. On the basis of these results, the possible mechanism of action of vanadate is discussed.
The Relationship between Development of Lung Inflammation and Changes in Bone Marrow Populations in Guinea-Pigs following Inhaled Antigen Challenge
Authors: Barton H.J. , Bond A. , Boot J.R. , Brandon D.R. , O’Brien A.
Published: August 2009

Sensitised guinea-pigs were exposed to aerosolised antigen. The resultant cellular infiltration into the lung was assessed in lung tissue and bronchoalveolar lavage fluid 6, 24, 72 h and 7 days later. An early neutrophil infiltration peaking at 6 h was succeeded by eosinophil migration which persisted for 7 days, at which time some of the eosinophils appeared immature. The lung eosinophilia was accompanied by an initial fall in eosinophilic cells in the bone marrow, followed by an increase in this population. Treatment with dexamethasone (25 mg/kg i.p.) given daily for 7 days after antigen challenge reduced the lung eosinophilia and observed bone marrow changes.
Purification and Characterization of Par· I, Major Allergen of Parietaria officinalis Pollen
Authors: Oreste U. , Coscia M.R. , Scotto d’Abusco A. , Santonastaso V.S. , Ruffilli A.
Published: August 2009

Par·I, a major allergen of Parietaria officinalis, was purified from the pollen extract. The purified allergen was obtained by ultrafiltration, Sephadex gel filtration and DE-52 ion exchange chromatography: the purified preparation yields a single band in polyacrylamide gel isoelectric focusing (PAG-IEF), sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting, a single immunoprecipitation arc in crossed immunoelectrophoresis (CIE) and crossed radioimmunoelectrophoresis (CRIE) and a single peak in size exclusion high-performance liquid chromatography (HPLC). Par·I is a glycoprotein with a protein to carbohydrate ratio of 100:21. The molecular weight, determined by SDS-PAGE, Sephadex G-50 gel filtration and size exclusion HPLC, varied between 13.5 and 14.5 kDa according to the method employed. The isoelectric point was 4.6. The amino acid composition and the sequence of the first twelve N-terminal residues were determined. The allergenicity was assayed in vivo and in vitro. 29/29 Parietaria-allergic patients were skin positive to Par·I and possessed high level of specific serum IgE antibody as it determined by radioallergosorbent test (RAST). Par·I contained dominant epitopes for human IgE as inhibited to 85% the pollen extract RAST performed with a pool of sera of allergic patients. The RAST inhibitory activity was not abolished by deglycosylation.
IgG Isotype Profiles Induced in Mice by Two Trypanosomacruzi Electronegative Antigens
Authors: Cerban F. , Gruppi A. , Gea S. , Vottero-Cima E.
Published: August 2009

In this work we studied the IgG isotypes induced in mice immunized with two Trypanosoma cruzi acidic antigenic fractions (F IV and Eas 4.5) and the level of protection to a later infection with parasites. F IV is a cytosolic antigen from epimastigotes, and Eas 4.5 is an exoantigen released by trypomastigotes. The most relevant epitopes of Eas 4.5 are carbohydrates. A high prevalence of IgG1, low levels of IgG3 and no IgG2 antibodies against F IV and Eas 4.5 were found in sera obtained 2 weeks after the last antigen dose from animals immunized with F IV (group I) or Eas 4.5 (group II). Immunized mice from both groups were infected with trypomastigotes, and the parasitemias detected later on were significantly lower than in control groups (p < 0.01, group I; p < 0.001, group II). The amount of IgG2-specific antibodies, which was only detected using epimastigotes as antigen in ELISA, was significantly increased after the infection, but no major changes were seen in the profiles of other isotypes.
Antiphospholipid Antibodies Reactive with Bromelain-Treated Mouse Erythrocytes in Mice, Rats and Rabbits
Authors: Kawaguchi S.
Published: August 2009

It has been reported that normal mice have a large number of B cells against bromelain-treated mouse erythrocytes (BrMRBC) and the anti-BrMRBC antibodies are reactive with liposomes of phosphatidylcholine and a phospholipid moiety of low-density lipoproteins from chicken egg yolk (EyLDL). In this study, we detected anti-BrMRBC hemolytic antibodies in the normal sera of rats and rabbits as well as mice. The antibodies in all the three species of animals bound to the columns of EyLDL. The EyLDL-binding antibodies could react with both liposomes of phosphatidylcholine and BrMRBC. The immunization with EyLDL evoked a vast production of anti-BrMRBC antibodies in rats and rabbits as well as mice. The anti-BrMRBC antibodies in the immunized animals could also react with liposomes of phosphatidylcholine. These findings suggest that rats and rabbits have the equivalent of mouse anti-BrMRBC B cells.
Effect of a Novel Antiallergic Drug, Pemirolast, on Activation of Rat Peritoneal Mast Cells: Inhibition of Exocytotic Response and Membrane Phospholipid Turnover
Authors: Fujimiya Hiroshi , Nakashima Shigeru , Miyata Hideo , Nozawa Yoshinori
Published: August 2009

The effects of a potent antiallergic drug, pemirolast (TBX), on activation of signal-transducing phospholipase C and A2, were examined in rat peritoneal mast cells. TBX at concentrations between 10––7 and 10––5 g/ml effectively inhibited degranulation in response to both antigen and compound 48/80. At the same concentrations the drug markedly suppressed the formation of 1,2-diacylglycerol and phosphatidic acid, and the decrease in phosphatidylinositol, suggesting the prevention of phospholipase C activation. The blockade of phospholipase A2 was suggested by the decrease in agonists-induced arachidonic acid liberation. These results indicate that TBX may exert its inhibitory effects on mast cells, at least in part, by preventing the activation of signal-transducing phospholipases.
Spontaneous Monokine Release by Alveolar Macrophages in Chronic Sarcoidosis
Authors: Strausz János , Männel Daniela N. , Pfeifer Sibylle , Borkowski Alexander , Ferlinz Rudolf , Müller-Quernheim Joachim
Published: August 2009

In pulmonary sarcoidosis an activation of alveolar T lymphocytes and alveolar macrophages (AM) has been demonstrated. There is evidence that in contrast to acute disease a heightened T-cell response cannot be observed in the chronic phase of sarcoidosis. The role of AM in the inflammatory process of chronic sarcoidosis is not yet intensively evaluated. To address this question we measured the release of tumor necrosis factor alpha (TNFα) and interleukin-1 (IL-1) by AM of 39 patients with chronic sarcoidosis (duration > 4 years; 30 active, 9 inactive diseases) without therapy and correlated the monokine release with parameters of T-cell alveolitis and the course of the disease. The T4/T8 ratio was higher in the active than in the inactive group without reaching statistical significance. TNFα as well as IL-1 is spontaneously released by AM of the active group 2,099 ± 518 pg/ml TNFα/106 cells/24 h and 8/13 (IL-l+/total) respectively. In the inactive group the AM release 375 ± 246 pg/ml TNFα/106 cells/24 h which is in the range of the control and 1 out of 5 patients was IL-1-positive. There was no correlation between the monokine release and any parameter of T-cell alveolitis. These data support the hypothesis that the inflammatory process in chronic sarcoidosis is dominated by the activity of AM and that this activity determines the course of the disease.
Characterization of Allergenic Components of Rye and Wheat Flour (Secale,Triticumvulgaris) by Western Blot with Sera of Bakers: Their Effects on CD23 Expression
Authors: Fränken J. , Stephan U. , Neuber K. , Bujanowski-Weber J. , Ulmer W.T. , König W.
Published: August 2009

The allergenic components of water-soluble rye flour extract were studied by immunoblotting. Sera from 100 bakers were analyzed for their IgG, IgG4 and IgE binding pattern. Two allergens with molecular weights of 35 and 14 kD were detected. Previously, the major allergens of wheat flour extract were identified. The wheat flour components at a MW of 15/17 kD and the rye flour component at a MW of 14 kD were purified and isolated. The modulation of the low affinity receptor for IgE (FcεRII/CD23) on monocytes by separated allergenic components was studied. Depending on the allergen concentration the CD23 expression on isolated cells increased after stimulation with the rye flour component (MW 14 kD). The combined addition of the rye flour component (14 kD) with IL-4 induced a significant CD23 expression as compared to IL-4 alone.
Strongyloidiasis Influences the Elevation of Adult T-Cell Leukemia-Associated Antigen Antibody Titer
Authors: Satoh Masao , Tsukidate Setsuko , Fujita Kohichiro , Yamamoto Kohtaro
Published: August 2009

We have carried out a seroepidemiological study on the infectious situation of adult T-cell leukemia and strongyloidiasis in Okinawa and in the south-western islands of Japan. The mean titer of adult T-cell leukemia virus-associated antigen (ATLA) antibody of human T-lymphotropic virus type-1 (HTLV-1) carriers with strongyloidiasis was significantly higher than that of HTLV-1 carriers without strongyloidiasis. This suggests the possibility that strongyloidiasis is also associated with an elevation of the ATLA antibody titer.
Tissue Factor and PAR2 Signaling in the Tumor Microenvironment
Authors: Schaffner Florence , Ruf Wolfram
Published: August 2009

Diverse oncogenic transformations result in the constitutive expression of tissue factor (TF) in cancer cells. The local and systemic activation of the coagulation cascade has long been a recognized hallmark for aggressive cancer, but genetic mouse models and new experimental therapeutics have only recently demonstrated crucial roles for TF initiated cell signaling in the pathogenesis of cancer. On tumor cells, the TF-VIIa binary complex mediates activation of protease activated receptor (PAR) 2 and thereby shapes the tumor microenvironment by inducing an array of proangiogenic and immune modulating cytokines, chemokines, and growth factors. PAR2 also uniquely triggers tumor cell migration by G protein–independent pathways through β-arrestin scaffolding. Metastatic tumor cells use additional signaling networks of the coagulation cascade by activating PAR1 through thrombin or the ternary TF-VIIa-Xa signaling complex in the vascular and potentially lymphatic system. Selective antagonists of TF-VIIa-PAR2 signaling may be used as antiangiogenic therapy without increasing the risk of bleeding, whereas coagulation and associated signaling pathways on platelets and other host cells may be targeted for therapeutic benefit in advanced cancer and metastatic disease.
Identification of Coagulation Factor XI as a Ligand for Platelet Apolipoprotein E Receptor 2 (ApoER2)
Authors: White-Adams Tara C. , Berny Michelle A. , Tucker Erik I. , Gertz Jacqueline M. , Gailani David , Urbanus Rolf T. , de Groot Philip G. , Gruber András , McCarty Owen J.T.
Published: August 2009

Objective—

Factor XI (FXI) promotes hemostasis and thrombosis through enhancement of thrombin generation and has been shown to play a critical role in the formation of occlusive thrombi in arterial injury models. The aim of this study was to investigate the mechanisms governing interactions between FXI and platelets.

Methods and Results—

Platelet adhesion to immobilized FXI was abrogated in the presence of the low-density lipoprotein (LDL) receptor antagonist, receptor-associated protein (RAP), soluble recombinant apolipoprotein E receptor 2 (ApoER2), or the LDL-binding domain 1 or 2 of ApoER2. FXI supported wild-type murine platelet binding; in contrast, ApoER2-deficient murine platelets did not adhere to FXI. In the presence of shear, platelet aggregates formed on FXI or activated FXI (FXIa) surfaces, whereas the presence of RAP, binding domain 1 of ApoER2, or an anti-GPIbα mAb blocked platelet adhesion to FXI or FXIa under shear. Soluble FXI bound to immobilized ApoER2′ with an affinity of 61 nmol/L.

Conclusions—

This study has identified apolipoprotein E receptor 2 (ApoER2, LRP8), a member of the LDL receptor family, as a platelet receptor for FXI. The interaction of FXI with other cell types that express ApoER2 remains to be explored.
Proteasome Inhibitors Enhance Endothelial Thrombomodulin Expression via Induction of Krüppel-Like Transcription Factors
Authors: Hiroi Toyoko , Deming Clayton B. , Zhao Haige , Hansen Baranda S. , Arkenbout Elisabeth K. , Myers Thomas J. , McDevitt Michael A. , Rade Jeffrey J.
Published: August 2009

Objective—

Impairment of the thrombomodulin–protein C anticoagulant pathway has been implicated in pathological thrombosis associated with malignancy. Patients who receive proteasome inhibitors as part of their chemotherapeutic regimen appear to be at decreased risk for thromboembolic events. We investigated the effects of proteasome inhibitors on endothelial thrombomodulin expression and function.

Methods and Results—

Proteasome inhibitors as a class markedly induced the expression of thrombomodulin and enhanced the protein C activating capacity of endothelial cells. Thrombomodulin upregulation was independent of NF-κB signaling, a principal target of proteasome inhibitors, but was instead a direct consequence of increased expression of the Krüppel-like transcription factors, KLF2 and KLF4. These effects were confirmed in vivo, where systemic administration of a proteasome inhibitor enhanced thrombomodulin expression that was paralleled by changes in the expression of KLF2 and KLF4.

Conclusions—

These findings identify a novel mechanism of action of proteasome inhibitors that may help to explain their clinically observed thromboprotective effects.
Hyperuricemia and Incident Heart Failure
Authors: Krishnan Eswar
Published: August 2009

Background—

Hyperuricemia, a known correlate of oxidative stress, is a marker for adverse prognosis among individuals with heart failure. However, the relationship between hyperuricemia and the risk for incidence of heart failure in a community-based population has not been studied.

Methods and Results—

We prospectively analyzed the relationship between serum uric acid concentration at baseline and subsequent heart failure among the participants of the Framingham Offspring cohort (n=4912; mean baseline age, 36 years; 52% women). By using Cox regressions, we calculated the risk of heart failure with increasing serum uric acid after adjusting for sex, age, smoking, body mass index, renal dysfunction, diuretics, systolic blood pressure, valvular heart disease, diabetes, alcohol, and use of antihypertensive medications. The incidence rates of heart failure were ≈6-fold higher among those at the highest quartile of serum uric acid (>6.3 mg/dL) compared with those at the lowest quartile (<3.4 mg/dL). The adjusted hazard ratio for the highest quartile of serum uric acid compared with the lowest was 2.1 (1.04 to 4.22). The relationship between hyperuricemia and heart failure was found in participants without metabolic syndrome and other subgroups as well.

Conclusions—

Hyperuricemia is a novel, independent risk factor for heart failure in a group of young general community dwellers. This has implications for development of preventive strategies for heart failure.
α1-Adrenergic Receptor Subtypes in Nonfailing and Failing Human Myocardium
Authors: Jensen Brian C. , Swigart Philip M. , De Marco Teresa , Hoopes Charles , Simpson Paul C.
Published: August 2009

Background—α1-adrenergic receptors (α1-ARs) play adaptive roles in the heart and protect against the development of heart failure. The 3 α1-AR subtypes, α1A, α1B, and α1D, have distinct physiological roles in mouse heart, but very little is known about α1 subtypes in human heart. Here, we test the hypothesis that the α1A and α1B subtypes are present in human myocardium, similar to the mouse, and are not downregulated in heart failure.

Methods and Results—Hearts from transplant recipients and unused donors were failing (n=12; mean ejection fraction, 24%) or nonfailing (n=9; mean ejection fraction, 59%) and similar in age (≈44 years) and sex (≈70% male). We measured the α1-AR subtypes in multiple regions of both ventricles by quantitative real-time reverse-transcription polymerase chain reaction and radioligand binding. All 3 α1-AR subtype mRNAs were present, and α1A mRNA was most abundant (≈65% of total α1-AR mRNA). However, only α1A and α1B binding were present, and the α1B was most abundant (60% of total). In failing hearts, α1A and α1B binding was not downregulated, in contrast with β1-ARs.

Conclusions—Our data show for the first time that the α1A and α1B subtypes are both present in human myocardium, but α1D binding is not, and the α1 subtypes are not downregulated in heart failure. Because α1 subtypes in the human heart are similar to those in the mouse, where adaptive and protective effects of α1 subtypes are most convincing, it might become feasible to treat heart failure with a drug targeting the α1A and/or α1B.
Tbx20 Interacts With Smads to Confine
Tbx2
Expression to the Atrioventricular Canal
Authors: Singh Reena , Horsthuis Thomas , Farin Henner F. , Grieskamp Thomas , Norden Julia , Petry Marianne , Wakker Vincent , Moorman Antoon F.M. , Christoffels Vincent M. , Kispert Andreas
Published: August 2009

Rationale
:

T-box transcription factors play critical roles in the coordinated formation of the working chambers and the atrioventricular canal (AVC). Tbx2 patterns embryonic myocardial cells to form the AVC and suppresses their differentiation into chamber myocardium.
Tbx20
-deficient embryos, which fail to form chambers, ectopically express
Tbx2
throughout the entire heart tube, providing a potential mechanism for the function of Tbx20 in chamber differentiation.

Objective
:

To identify the mechanism of
Tbx2
suppression by Tbx20 and to investigate the involvement of Tbx2 in Tbx20-mediated chamber formation.

Methods and Results
:

We generated
Tbx20
and
Tbx2
single and double knockout embryos and observed that loss of
Tbx2
did not rescue the
Tbx20
-deficient heart from failure to form chambers. However, Tbx20 is required to suppress
Tbx2
in the developing chambers, a prerequisite to localize its strong differentiation-inhibiting activity to the AVC. We identified a bone morphogenetic protein (Bmp)/Smad-dependent
Tbx2
enhancer conferring AVC-restricted expression and Tbx20-dependent chamber suppression of
Tbx2
in vivo. Unexpectedly, we found in transfection and localization studies in vitro that both Tbx20 and mutant isoforms of Tbx20 unable to bind DNA attenuate Bmp/Smad-dependent activation of
Tbx2
by binding Smad1 and Smad5 and sequestering them from Smad4.

Conclusions
:

Our data suggest that Tbx20 directly interferes with Bmp/Smad signaling to suppress
Tbx2
expression in the chambers, thereby confining
Tbx2
expression to the prospective AVC region.
Heat Shock Protein 70 Enhances Vascular Bone Morphogenetic Protein-4 Signaling by Binding Matrix Gla Protein
Authors: Yao Yucheng , Watson Andrew D. , Ji Sheng , Boström Kristina I.
Published: August 2009

Rationale:

Matrix Gla protein (MGP) is a calcification inhibitor, which binds and inhibits bone morphogenetic protein (BMP)-2 and -4.

Objective:

The objective was to determine whether MGP also binds other proteins, which could interfere with its function.

Methods and Results:

We transfected bovine aortic endothelial cells with N-terminally FLAG-tagged MGP and used immunoprecipitation and liquid chromatographic–tandem mass spectrometric analysis to identify MGP-binding proteins. Heat shock protein (HSP)70, a stress-induced protein expressed in atherosclerotic lesions and soluble in serum, was identified as a novel MGP-binding protein. The interaction between MGP and HSP70 was confirmed by coimmunoprecipitation and chemical crosslinking, and blocked the interaction between MGP and BMP-4. In endothelial cells, HSP70 enhanced BMP-4–induced proliferation and tube formation, and in calcifying vascular cells, HSP70 enhanced BMP-induced calcium deposition. In addition, HSP70 mediated the procalcific effect of interleukin-6 on calcifying vascular cells. In apolipoprotein E–null mice, a model for atherosclerosis, levels of BMP-4, HSP70, MGP, and interleukin-6 were elevated in the aortic wall. Levels of BMP-4, HSP70, and interleukin-6 were also elevated in serum, and anti-HSP70 antibodies diminished its procalcific effect on calcifying vascular cells.

Conclusion:

HSP70 binds MGP and enhances BMP activity, thereby functioning as a potential link between cellular stress, inflammation, and BMP signaling.
Brief Psychosocial–Behavioral Intervention With Antidepressant Reduces Poststroke Depression Significantly More Than Usual Care With Antidepressant
Authors: Mitchell Pamela H. , Veith Richard C. , Becker Kyra J. , Buzaitis Ann , Cain Kevin C. , Fruin Michael , Tirschwell David , Teri Linda
Published: August 2009

Background and Purpose—

Depression after stroke is prevalent, diminishing recovery and quality of life. Brief behavioral intervention, adjunctive to antidepressant therapy, has not been well evaluated for long-term efficacy in those with poststroke depression.

Methods—

One hundred one clinically depressed patients with ischemic stroke within 4 months of index stroke were randomly assigned to an 8-week brief psychosocial–behavioral intervention plus antidepressant or usual care, including antidepressant. The primary end point was reduction in depressive symptom severity at 12 months after entry.

Results—

Hamilton Rating Scale for Depression raw score in the intervention group was significantly lower immediately posttreatment (
P
<0.001) and at 12 months (
P
=0.05) compared with control subjects. Remission (Hamilton Rating Scale for Depression <10) was significantly greater immediately posttreatment and at 12 months in the intervention group compared with the usual care control. The mean percent decrease (47%±26% intervention versus 32%±36% control,
P
=0.02) and the mean absolute decrease (−9.2±5.7 intervention versus −6.2±6.4 control,
P
=0.023) in Hamilton Rating Scale for Depression at 12 months were clinically important and statistically significant in the intervention group compared with control.

Conclusion—

A brief psychosocial–behavioral intervention is highly effective in reducing depression in both the short and long term.
Relation of Candidate Genes that Encode for Endothelial Function to Migraine and Stroke
Authors: MacClellan Leah R. , Howard Timothy D. , Cole John W. , Stine O. Colin , Giles Wayne H. , O'Connell Jeffery R. , Wozniak Marcella A. , Stern Barney J. , Mitchell Braxton D. , Kittner Steven J.
Published: August 2009

Background and Purpose—

Migraine with aura is a risk factor for ischemic stroke, but the mechanism by which these disorders are associated remains unclear. Both disorders exhibit familial clustering, which may imply a genetic influence on migraine and stroke risk. Genes encoding for endothelial function are promising candidate genes for migraine and stroke susceptibility because of the importance of endothelial function in regulating vascular tone and cerebral blood flow.

Methods—

Using data from the Stroke Prevention in Young Women study, a population-based case-control study including 297 women aged 15 to 49 years with ischemic stroke and 422 women without stroke, we evaluated whether polymorphisms in genes regulating endothelial function, including endothelin-1 (
EDN
), endothelin receptor type B (
EDNRB
), and nitric oxide synthase-3 (
NOS3
), confer susceptibility to migraine and stroke.

Results—

EDN
SNP rs1800542 and rs10478723 were associated with increased stroke susceptibility in whites (OR, 2.1; 95% CI, 1.1–4.2 and OR, 2.2; 95% CI, 1.1–4.4;
P
=0.02 and 0.02, respectively), as were
EDNRB
SNP rs4885493 and rs10507875, (OR, 1.7; 95% CI, 1.1–2.7 and OR, 2.4; 95% CI, 1.4–4.3;
P
=0.01 and 0.002, respectively). Only 1 of the tested SNP (
NOS3
rs3918166) was associated with both migraine and stroke.

Conclusions—

In our study population, variants in
EDN
and
EDNRB
were associated with stroke susceptibility in white but not in black women. We found no evidence that these genes mediate the association between migraine and stroke.
Infarct Volume is a Major Determiner of Post-Stroke Immune Cell Function and Susceptibility to Infection
Authors: Hug Andreas , Dalpke Alexander , Wieczorek Nina , Giese Thomas , Lorenz Alexander , Auffarth Gerd , Liesz Arthur , Veltkamp Roland
Published: August 2009

Background and Purpose—

Acute ischemic stroke in humans is associated with profound alterations in the immune system. Hallmarks of this stroke-induced immunodepression syndrome are: lymphocytopenia, impairment of T helper cell and monocyte function. We studied which stroke-specific factors predict these immunologic alterations and subsequent infections.

Methods—

Leukocyte/lymphocyte subsets were assessed serially by white blood cell count and fluorescence-activated cell sorter analysis in ischemic stroke patients (n=50) at baseline, day 1, and day 4 after stroke onset and compared to an age-matched control group (n=40). Concomitantly, monocytic human leukocyte antigen-DR expression and the in vitro function of blood monocytes measured by the production of tumor necrosis factor-α upon stimulation with lipopolysaccharide were assessed. Associations of these immunologic parameters with stroke specific factors (National Institutes of Health Stroke Scale, infarct size) were explored. Multivariable logistic regression analysis was applied to identify early predictors for poststroke respiratory and urinary tract infections.

Results—

Infarct volume was the main factor associated with lymphocytopenia on day 1 and day 4 poststroke. Particularly, blood natural killer cell counts were reduced after stroke. Monocyte counts increased after ischemia paralleled by a profound deactivation predominantly after extensive infarcts. Reduced T helper cell counts, monocytic human leukocyte antigen-DR expression, and monocytic in vitro production of tumor necrosis factor-α were associated with infections in univariate analyses. However, only stroke volume prevailed as independent early predictor for respiratory infections (OR 1.03; CI 1.01 to 1.04).

Conclusions—

Infarct volume determines the extent of lymphocytopenia, monocyte dysfunction, and is a main predictor for subsequent infections.
Pre-Reading Mammograms by Specialised Breast Technologists: Legal Implications for Technologist and Radiologist in the Netherlands
Authors: de Bijl N.P.Y.M. , Flobbe  , van den Biggelaar F.J.H.M. , van Engelshoven J.M.A.
Published: August 2009

This paper focuses on the legal implications in terms of duties and responsibilities for radiologists and radiologic technologists of independent pre-reading of mammograms by radiologic technologists, so patients could be discharged without being seen by a radiologist. Pre-reading could be effectuated when preconditions are met to perform reserved procedures by unauthorised professionals as stated in the Individual Health Care Professions (IHCP) Act. Furthermore, compliance with a protocol or code of conduct in combination with adequate training and supervision should be sufficient to disprove potential claims. For a wide implementation, pre-reading should be well-embedded in legal rules and should answer the professional standard of care.
Comparisons of Musculoskeletal Complaints and Data Entry Between a Sitting and a Sit-Stand Workstation Paradigm
Authors: Husemann Britta , Von Mach Carolin Yvonne , Borsotto Daniel , Zepf Kirsten Isabel , Scharnbacher Jutta
Published: August 2009

Background: Seated working positions are often regarded as a cause for discomfort in the musculoskeletal system. Performing work in different working positions—that is, alternating between sitting and standing (sit-stand workstation paradigm)—could help reduce physical complaints. Objective: The questions were whether performing office work partly in a standing position leads to reduced complaints and whether standing would change the efficiency of data entry office work. Method: We investigated the effect of a sit-stand workstation paradigmd during experimental data entry office work on physical and psychological complaints and data entry efficiency by conducting a randomized controlled trial with 60 male participants ages 18 to 35 years. Results: In this experiment, musculoskeletal complaints were reduced by a sit-stand workstation paradigm. A trend could be identified indicating a small but nonsignificant loss of efficiency in data entry while standing. Conclusion: A sit-stand workstation paradigm reduces musculoskeletal complaints without considerably affecting data entry efficiency under the presented study conditions (young male participants, short duration, fixed and controlled sit-stand workstation paradigm, simulated experimental working condition). Application: According to the present data, implementing a sit-stand workstation paradigm can be an effective workplace health intervention to reduce musculoskeletal complaints. This experiment encourages further studies on the effectiveness of a sit-stand workstation paradigm. Experimental research and field studies that prove the reduction of complaints when introducing a sit-stand workstation paradigm in the workplace could be the basis for evidence-based recommendations regarding such interventions.
What Is in a Name?
Authors: Weber Shirley N.
Published: August 2009

The essay explains the origins of the discussion of naming in the discipline. The late Dr. William Little, former president of the National Council for Black Studies (NCBS), called upon the NCBS to lead the nation in confronting the controversy of standardizing what departments should be called based upon the curriculum being offered. This volume is dedicated in his memory.
Spelling Our Proper Name
Authors: Furusa Munashe
Published: August 2009

This article examines internal and external intellectual discourses that have developed around Africana Studies as an academic discipline within the United States from its inception to the present. It explores intellectual constructs and discursive contexts that have shaped the variations, complexities, and contradictions in the conceptualization, scope, and philosophical direction of Africana Studies as a discipline. It argues that the name or names of the discipline should reflect the nature and scope, curriculum content and structure, declared goals and expected outcomes of Africana Studies.
Comparison of Interaction of Aromatic Solvents in Hybrid and Textile Biocomposites
Authors: John Maya Jacob , Thomas Sabu , Varughese K.T.
Published: August 2009

Natural rubber was reinforced with sisal—oil palm hybrid fibers. Composites were prepared by varying the weight content of the fibers and chemical modification of the biofibers. The interaction of three different types of aromatic solvents, namely, benzene, toluene, and xylene with the rubber composites was analyzed. Textile composites were also prepared by sandwiching a single sheet of sisal fabric between two pre-weighed rubber sheets. The diffusion behavior of the textile composites in benzene, toluene, and xylene was also analyzed. The mechanics of diffusion was found to be different for hybrid and textile biocomposites. The swelling index factor was also calculated for all the composites. Swelling was found to be predominantly dependent on the aromatic solvent used and chemical treatments. Chemically modified composites were found to be less prone to solvent permeation.
Breast cancer diagnosis using an artificial neural network trained by group search optimizer
Authors: He S. , Wu Q.H. , Saunders J.R.
Published: August 2009

This paper presents a novel optimization algorithm: a group search optimizer (GSO) for training an artificial neural network (ANN) used for diagnosis of breast cancer. The GSO is inspired by animal social searching behaviour. Its global search performance has been proved competitive to other evolutionary algorithms and the particle swarm optimizer. The parameters of a three-layer feed-forward ANN, including connection weights and bias are tuned by the GSO algorithm. Wisconsin diagnostic breast cancer data from the UCI Machine Learning repository are employed as a benchmark classification problem to evaluate the proposed method. In comparison with other sophisticated machine learning techniques used for ANN training, including some ANN ensembles, the GSO for ANN, GSOANN, has a better convergence rate and generalization performances for the breast cancer diagnosis problem.
Robust performance design of single-input fuzzy control system for plant with time delay
Authors: Yordanova S.
Published: August 2009

Fuzzy logic has recently gained popularity in the development of robust non-linear control convenient for real-time applications, satisfying the high-performance requirements of the control systems by dealing with data imprecision and noise. There are, however, problems in designing a unique controller that will provide system stability and desirable performance in the presence of plant model uncertainties and time delays. The aim of this investigation is to develop a simple approach for the design of an incremental PI-like single-input fuzzy controller (SI FC) that ensures a robust performance in the closed-loop system for the control of industrial plants with time delays and model uncertainties. The main results are: 1) derivation of a robust performance criterion of the SI FC system in the frequency domain, employing the stabilization of the system linear part, the linearization of the fuzzy unit and the Popov stability approach; 2) development of an SI FC tuning algorithm; 3) application of the design approach for the control of air temperature in a furnace using MATLAB TM, and assessment of the advantages over an ordinary PI controller. The designed SI FC preserves system stability and performance for a high range of plant model uncertainties.