bluuebunny/crossref_metadata_2025_split huggingface dataset:
Localization of a Recessive Juvenile Cataract Mutation to Proximal Chromosome 7 in Mice
Authors: Cargill E.J. , Happold T.R. , Bertani G. , Rocha J. , Lou M.F. , Pomp D. , Nielsen M.K. 
Published: April 2003

<i>Objective:</i> To localize the chromosomal position of a novel cataract mutation (juvenile recessive cataract; <i>jrc</i>) in mice. <i>Methods:</i> A mapping population was developed by crossing cataract males (albino MH) to wild-type females (black C57BL/6J). F<sub>1</sub> females were backcrossed to albino MH males with cataracts. <i>Results:</i> The results were consistent with a model of a single autosomal recessive gene [153 cataract, 169 wild-type; χ<sup>2</sup> = 0.8, 1 degree of freedom (d.f.), p > 0.35]. Linkage with the albino (tyrosinase; <i>Tyr</i>) locus was evident (χ<sup>2</sup> = 61.5, 1 d.f., p < 0.0001), implicating chromosome 7 as the location of <i>jrc</i>. Recombination percentages (± SE) between <i>jrc</i> and <i>D7Mit340</i> (1.2 cM location), <i>D7Mit227</i> (16.0 cM) and <i>D7Mit270</i> (18.0 cM) were 17.1 ± 2.1, 3.7 ± 1.1 and 6.2 ± 1.3%, respectively. Multi-point mapping determined that the most likely order of these loci is <i>D7Mit340</i> – <i>jrc</i> – <i>D7Mit227</i> – <i>D7Mit270</i> – <i>Tyr</i>. Although animals with the mutant phenotype appeared to have little or no sense of sight, their growth was not different (p >0.20) from that of normal mice. <i>Conclusion:</i> The <i>jrc</i> mutation model may be useful in the study of the genetics of cataracts in other animal species, including humans.
Functional Expression of Transmembrane 4 Superfamily Molecules on Human Eosinophils
Authors: Matsumoto Kenji , Bochner Bruce S. , Wakiguchi Hiroshi , Kurashige Takanobu 
Published: April 2003

<i>Background:</i> Transmembrane 4 superfamily (TM4SF) molecules are exclusively found on hematopoietic cells. Several members of the TM4SF are reported to be associated with other cell surface molecules, including integrins, and might participate in signal transduction, but little is known about their role on eosinophils. In the present study, we determined the expression and function of TM4SF molecules on human eosinophils. <i>Methods:</i> Surface expression of TM4SF molecules on purified peripheral blood eosinophils was examined using indirect immunofluorescence and flow cytometry. Purified eosinophils were incubated with anti-TM4SF monoclonal antibodies (mAbs) for up to 24 h. Eosinophil activation was evaluated by measuring eosinophil homotypic aggregation as well as changes in surface expression of CD11b or CD62L by flow cytometry. <i>Results:</i> Freshly isolated eosinophils expressed CD9, CD37, CD53, CD63 and CD81. Incubation with anti-CD9 mAb but not with anti-CD37, CD53, CD63 or CD81 mAb induced significant eosinophil homotypic aggregation. Incubation with any of the anti-TM4SF mAb for 30 min failed to alter the expression of either CD11b or CD62L on eosinophils. In contrast, the expression of CD11b was significantly enhanced after 24 h of incubation with anti-CD53 mAb, while the expression of CD62L was significantly reduced with anti-CD81 mAb. <i>Conclusions: </i>Cross-linking of some surface TM4SF molecules induced significant eosinophil homotypic aggregation, upregulation of CD11b expression, or CD62L shedding, consistent with activation of eosinophils. Our data suggest that several TM4SF molecules are functionally expressed on human eosinophils, and therefore might participate in allergic inflammation.
Circadian Variation in Nasal Reactivity in Children with Allergic Rhinitis: Correlation with the Activity of Eosinophils and Basophilic Cells
Authors: Aoyagi Masahiko , Watanabe Hiroko , Sekine Kunio , Nishimuta Toshiyuki , Konno Akiyoshi , Shimojo Naoki , Kohno Yoichi 
Published: April 2003

<i>Background:</i> In allergic rhinitis, the major symptoms of runny nose, sneezing, and stuffy nose tend to become worse upon waking up in the morning, and yet the mechanisms underlying this phenomenon are poorly understood. We investigated whether the worsening of allergic rhinitis in the morning is associated with changes in the activity of inflammatory cells. <i>Methods:</i> Nasal reactivity to methacholine was assessed twice in 8 children with allergic rhinitis and 8 healthy control subjects at 6.00 a.m. and 3.00 p.m. The amounts of eosinophil cationic protein (ECP), histamine and tryptase in induced nasal secretions and peripheral blood were also measured. <i>Results:</i> Nasal reactivity to methacholine was higher at 6.00 a.m. not only in patients but also in healthy controls. Serum ECP and plasma histamine levels showed no circadian patterns. On the other hand, significantly higher levels of inflammatory activation products were found in nasal secretions at 6.00 a.m., thus showing a direct association with nasal reactivity. <i>Conclusion:</i> These results suggest that the circadian variation in nasal reactivity is associated with changes in the activity of eosinophils and basophilic cells in the nasal mucosa.
Role of Secretory IgA, Secretory Component, and Eosinophils in Mucosal Inflammation
Authors: Motegi Youichi , Kita Hirohito , Kato Masahiko , Morikawa Akihiro 
Published: April 2003

Eosinophils and their products are important in the pathophysiology of allergic inflammation in mucosal tissues. Secretory component (SC) bound to IgA mediates transepithelial transport of IgA. As another biological activity of SC, we have reported that secretory IgA (sIgA) and SC preferentially activate human eosinophils. When eosinophils were stimulated with immobilized sIgA, degranulation and superoxide production were greater than when stimulated with serum IgA. In contrast, neutrophils responded similarly to sIgA and serum IgA. Superoxide production by eosinophils stimulated with cytokines was enhanced synergistically by immobilized SC, while SC showed no effect on neutrophil activation. Eosinophil superoxide production stimulated with sIgA was abolished by anti-CD18 mAb, suggesting that β2 integrins might be crucial for this reaction. There are several reports that SC and sIgA may play important roles in regulating eosinophil functions in vivo in diseases associated with mucosal eosinophilia and in various allergic diseases. It is speculated that eosinophils in the mucosa are activated by SC or sIgA, and that subsequent degranulation and superoxide production are induced.
Effect of Aerosolized Docosahexaenoic Acid in a Mouse Model of Atopic Asthma
Authors: Yokoyama Akihito , Hamazaki Tomohito , Ohshita Akira , Kohno Nobuoki , Sakai Kimiko , Zhao Guang-Dong , Katayama Hitoshi , Hiwada Kunio 
Published: April 2003

<i>Background:</i> Docosahexaenoic acid (DHA) found in fish oil is known to depress inflammation-related mediators. We investigated a novel delivery method of tridocosahexaenoyl-glycerol (DHA-TG). <i>Methods:</i> BALB/c mice (6–8 weeks old) were primed intraperitoneally with ovalbumin (OVA) and Al(OH)<sub>3</sub> on days 0 and 7, and with aerosolized OVA on day 7. Primed mice were challenged by repeated exposure to aerosolized OVA on days 15–17. Just before each exposure to aerosolized OVA, the mice were also exposed to an aerosol of emulsified DHA-TG or soybean oil, or saline (days 7 and 15–17). Bronchial hyperresponsiveness (BHR) to methacholine was measured, and bronchoalveolar lavage fluid was obtained 24 h after the last challenge (day 18). Lungs were histologically examined. <i>Results:</i> Bronchoalveolar lavage fluid of saline-treated mice showed an increased cellularity with predominant eosinophils. Exposure to DHA-TG significantly reduced the total cell number and the eosinophil percentage in lavage fluid, whereas soybean oil did not. <i>Conclusion:</i> DHA but not soybean oil exposure reduced BHR and cell infiltration to bronchovascular bundles. This type of DHA administration could be studied in clinical trials.
Characterization of α5-Integrin-Dependent Mast Cell Adhesion following FcεRI Aggregation
Authors: Dastych Jaroslaw , Wyczółkowska Janina , Metcalfe Dean D. 
Published: April 2003

<i>Background:</i> Integrin receptors are engaged in the upregulation of mast cell adhesion to extracellular matrix components upon stimulation with cytokines and antigen. Fibronectin receptor containing the α5-integrin subunit is critical for mast cell interaction with the extracellular matrix protein fibronectin (FN). <i>Methods:</i> The murine MCP5/L mast cell line was employed to investigate the process of Fc&#917;RI-mediated mast cell adhesion to FN. RT-PCR and cytofluorimetric analysis were used to assess the expression of α5 integrin in MCP5/L mast cells. Radiolabelled mast cells were sensitized with monoclonal IgE and used in adhesion assays. Anti-α5-integrin antibody (Ab), monovalent hapten and metabolic inhibitors were used to characterize antigen-mediated mast cell adhesion to FN. <i>Results:</i> Addition of antigen to IgE-sensitized cells resulted in transient upregulation of mast cell adhesion to FN with a maximum adhesion following 30 min of incubation. Mast cell adhesion was inhibited with anti-α5-integrin monoclonal antibodies blocking FN receptor or with excess monovalent hapten preventing antigen-mediated IgE cross-linking. The presence of the protein kinase C (PKC) inhibitor staurosporine also inhibited mast cell adhesion in a dose-dependent fashion. The process of Fc&#917;RI-mediated upregulation of mast cell adhesion to FN was not associated with an increase in surface expression of mast cell FN receptors. <i>Conclusion:</i> The major FN receptor on MCP5/L mast cell surface, an integrin containing the α5 subunit mediates a transient change in mast cell adhesiveness following IgE cross-linking. Fc&#917;RI-derived signals engage PKC and upregulate mast cell adhesion in a process which might involve changes in integrin avidity rather than integrin expression.
Chemoattractant Receptors Expressed on Type 2 T Cells and Their Role in Disease
Authors: Cosmi Lorenzo , Annunziato Francesco , Maggi Enrico , Romagnani Sergio , Manetti Roberto 
Published: April 2003

The existence of two functionally distinguished populations among T cells has been established in both mice and humans. Type 1 T helper (Th1) cells are involved in the defense against intracellular bacteria and many viruses, while type 2 Th cells (Th2) are the major actors in the response against parasites and play a central role in allergic inflammation. More recently, several data have suggested that some chemokine receptors are tightly regulated on T cells, and in accordance with this selective expression, Th1 and Th2 cells can be differentially recruited by specific chemokines to the inflammatory sites. Among Th2-associated chemokine receptors, CCR3, CCR4 and CCR8 have been described to play a central role in allergic inflammation. However, CCR3 is mainly expressed on basophils, eosinophils and mast cells, but it is poorly expressed by Th2 cells, and CCR4 is also expressed by Th subsets different from Th2 cells. So far, the chemoattractant receptors which among T cells appear to be selectively expressed by Th2 cells or their subsets are CCR8 and CRTH2. The ligand for CRTH2 is not a chemokine, but is prostaglandin (PG)D2, which is able to attract basophils, eosinophils, Th2 cells and type 2 cytotoxic (Tc2) CD8+ T lymphocytes. The selective expression of CRTH2 on Th2 and Tc2 cells may be useful to develop new therapeutic strategies against allergic diseases and against other immune disorders. Additional studies, however, are required to understand its effective importance in the induction and maintenance of Th2- or Tc2-mediated response and inflammation.
Theophylline Inhibits TNF-α-Induced CD4 Expression on Human Eosinophils and CD4+ Eosinophil Migration
Authors: Tsukadaira Akihiro , Okubo Yoshio , Horie Shiro , Koyama Sekiya 
Published: April 2003

<i>Background: </i>Increasing evidence regarding asthma suggests that CD4+ cells are preferentially recruited to sites of bronchial inflammation. Interleukin (IL)-16 has been reported as playing an important role in the accumulation of CD4+ cells. We have shown that the CD4 molecule is expressed on normal human eosinophils by tumor necrosis factor (TNF)-α stimulation. <i>Methods: </i>We evaluated the effects of theophylline, KF19514 [a selective phosphodiesterase (PDE) IV inhibitor] and dexamethasone on CD4 expression on eosinophils and eosinophil migration in response to IL-16, a natural soluble ligand of the CD4 molecule. <i>Results: </i>The maximum eosinophil migration was observed when eosinophils were cultured with TNF-α at 10 ng/ml for 18 h and the concentration of IL-16 was 10 pg/ml. CD4+ eosinophil migration in response to IL-16 was mostly, if not fully, chemokinetic and this migration was significantly inhibited by Fab of anti-CD4 monoclonal antibody. Theophylline (10<sup>–4</sup>–10<sup>–3</sup><i>M</i>), KF19514 (10<sup>–7</sup>–10<sup>–6</sup><i>M</i>) and dexamethasone (10<sup>–8</sup>– 10<sup>–6</sup><i>M</i>) significantly inhibited CD4 expression on eosinophils induced by TNF-α. Theophylline (10<sup>–3</sup><i>M</i>) and KF19514 (10<sup>–6</sup><i>M</i>) inhibited CD4+ eosinophil migratory responses induced by IL-16, but 10<sup>–6</sup><i>M</i> dexamethasone did not. Theophylline and KF19514 augmented the intracellular adenosine-3′,5′-cyclic monophosphate (cAMP) concentration in eosinophils, suggesting modulation by cAMP of CD4 expression and eosinophil migration. <i>Conclusions: </i>These data suggest that TNF-α-induced CD4+ eosinophils may contribute to eosinophil migratory responses induced by IL-16. Theophylline and selective PDE IV inhibitor may prevent airway inflammation by downregulating CD4 expression on eosinophils and inhibiting eosinophil migration through CD4 and IL-16 interaction.
Leukocyte Adhesion after Oxidant Challenge in the Hamster Cheek Pouch Microcirculation
Authors: Bouskela E. , Cyrino F.Z.G.A. , Lerond L. 
Published: April 2003

Oral administration of S-5682 (Daflon 500 mg, 90% diosmin, 10% hesperidin) inhibits oxidant-induced increase in macromolecular permeability in the postcapillary venules of the hamster cheek pouch microcirculation. In this study, the effect of S-5682 on leukocyte-endothelium interaction was evaluated using the same experimental model. Hamsters kept on a standard diet were divided into 5 groups (n = 6) and treated orally, twice a day, with placebo (10% lactose solution), S-5682, 5, 20 or 80 mg/kg/day (suspended in 10% lactose solution) or α-tocopherol, 1 mg/kg/day, for 10 days prior to the oxidant challenge with tert-butylhydroperoxide (TBOOH). Topical application of TBOOH (10<sup>–4</sup> <i>M</i> for 5 min) to hamsters given acridine orange prior to TBOOH resulted in increases in the number of rolling and sticking (no movement for at least 30 s) leukocytes in postcapillary venules. No changes in the number of rolling leukocytes could be observed in the treated groups compared with the placebo group (p > 0.05). On the contrary, leukocyte adhesion was inhibited in groups treated with S-5682 (5, 20 and 80 mg/kg/day) or α-tocopherol: placebo 105 ± 3/6 mm<sup>2</sup> (mean ± SEM); S-5682, 5 mg/kg/day 68 ± 3/6 mm<sup>2</sup> (p < 0.01), 20 mg/kg/day 55 ± 3/6 mm<sup>2</sup> (p < 0.001) and 80 mg/ kg/day 39 ± 2/6 mm<sup>2</sup> (p < 0.001) and α-tocopherol 36 ± 1/6 mm<sup>2</sup> (p < 0.001). The inhibition of oxidant-induced leukocyte adhesion by S-5682 was similar to that seen for ischemia-reperfusion and the higher dose of S-5682 was as effective as α-tocopherol in inhibiting it.
Venous Ulcer Reappraisal: Insights from an International Task Force
Authors: Clement D.L. 
Published: April 2003

An international task force made up of a panel of 16 experts was mandated to review and objectively evaluate all aspects of chronic venous disease of the leg. All available publications on chronic venous disease of the leg from 1983 to 1997 were identified through computerized search. Three different screenings were then performed in order to select only relevant papers providing moderate to strong scientific evidence. Final conclusions and further therapeutic recommendations were made based on these publications. Compression, medications, local therapies, sclerotherapy and surgery are the existing therapeutic options for which the following recommendations can be made. Compression: Properly applied bandages both fixed and stretched have been shown to be effective. Compression stockings may be used. Compression needs to be in excess of 35 mm Hg. Medications: Although preliminary results have shown a beneficial effect of several vasodilators and oral micronized purified flavonoid fraction, the evidence for the efficacy of medications on venous ulcer healing is still limited and further studies are required before recommendations can be made. There is no evidence to routinely administer antibiotics. Local therapies have an as yet unproven adjunctive role. Sclerotherapy is unlikely to be effective unless there is superficial venous insufficiency, in which it may have an as yet unproven role. Surgery: Patients with active venous ulcer and sapheno-femoral or sapheno-popliteal junction incompetence benefit from surgical treatment. In the absence of reflux or following deep vein thrombosis, there is no evidence to support surgical treatment.
Transition of Apoptotic Resistant Vascular Smooth Muscle Cells to Troptotic Sensitive State Is Correlated with Downregulation of c-FLIP
Authors: Imanishi Toshio , Hano Takuzo , Nishio Ichiro , Liles W. Conrad , Schwartz Stephen M. , Han David K.M. 
Published: April 2003

Fas and its ligand, FasL, are a receptor-ligand pair identified as promoting cell death in several tissues. Vascular smooth muscle cells (VSMCs) are resistant to FasL or anti-Fas antibody (Ab) signal, and a number of in vitro studies show that VSMC death can only be induced by anti-Fas Ab or FasL in the presence of protein inhibitor or additional inflammatory mediators. It remains to be clarified whether known, constitutively expressed cytoprotective molecules are reduced by protein inhibitor, thereby accounting for sensitization to cell death by Fas/FasL signaling. We found that Fas mRNA and protein exist in several primary VSMCs, as previously reported. We also demonstrated (1) that critical death-signaling molecules, such as FADD, caspase-1/ICE, and caspase-3/YAMA, are present in these VSMCs, (2) that human VSMCs contain high concentrations of c-FLIP (3) and that following treatment with the protein inhibitor, CHX, cell extracts showed a decrease in c-FLIP protein that was dose- and time-dependent on the degree of apoptosis and inversely correlated with both caspase-8 and -3 activity. In contrast, there was neither a change nor an even modest upregulation of Bcl-2 family, even after 12 h of treatment with CHX. Taken together, these results may provide a novel insight into atherogenesis and suggest that c-FLIP may contribute to an apoptosis-resistant state of VSMC, and that a downregulation of c-FLIP may render VSMCs susceptible to apoptosis.
Deep Venous Thrombosis: Leukocyte Rheology at Baseline and after in vitro Activation
Authors: LoPresti R. , Ferrara F. , Canino B. , Montana M. , Caimi G. 
Published: April 2003

We evaluated leukocyte rheology, expressed as leukocyte filtration, polymorphonuclear (PMN) membrane fluidity and cytosolic Ca<sup>2+</sup> concentration in subjects with acute deep venous leg thrombosis (DVT). In 14 subjects with leg DVT we examined the leukocyte filtration [unfractionated, mononuclear cells (MN), PMNs], PMN membrane fluidity and PMN cytosolic Ca<sup>2+</sup> concentration. Subsequently, we evaluated the same PMN variables after in vitro chemotactic activation with 4-phorbol-12-myristate-13-acetate. At baseline, we observed a significant difference in the filtration of unfractionated and MNs and in PMN cytosolic Ca<sup>2+</sup> concentration. After PMN activation, a significant variation, greater in DVT subjects, was present in PMN filtration at 5 and 15 min. In normals, no variation was present in PMN membrane fluidity or cytosolic Ca<sup>2+</sup> concentration after activation, while in subjects with DVT we found a significant variation in both PMN parameters. These results underline that there is a systemic leukocyte functional alteration in DVT.
Absence of Transplacental Passage of the Low Molecular Weight Heparin Enoxaparin
Authors: Dimitrakakis Constantine , Papageorgiou Panayiotis , Papageorgiou Ioannis , Antzaklis Aris , Sakarelou Nafsika , Michalas Stylianos 
Published: April 2003

<i>Background:</i> Venous thromboembolism (VTE) during pregnancy and puerperium remains a major cause of maternal morbidity and mortality. The use of low molecular weight heparin (LMWH) constitutes a promising alternative for the prevention of VTE instead of unfractionated heparin as it can be administered subcutaneously once daily and without coagulation measurement. Unfortunately, the safety of LMWHs administration for the mother and fetus has not been well established. <i>Study Design:</i> In order to examine the safety of enoxaparin to the fetus, 24 women were recruited and 40 mg of enoxaparin was administered in 14 of them. All 24 women were going to have an early termination of pregnancy due to major fetal malformations. Maternal blood samples were drawn before and after the injection of enoxaparin, while fetal blood samples were taken only after the drug administration. Anti-IIa and anti-Xa activities were measured. <i>Results:</i> A statistically significant increase of anti-Xa activity in the mothers studied was pointed out, while there was no detection of anti-IIa and anti-Xa activities in the fetuses. <i>Conclusions:</i> Since no anti-IIa and anti-Xa activities were detected in the fetuses’ blood samples, it is concluded that enoxaparin does not cross the placenta and therefore appears safe for the fetus.