bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyanotic Breath-Holding Spell: A Life-Threatening Complication after Radical Resection of a Cervicomedullary Ganglioglioma
Authors: Fujisawa Hironori , Yoshida Yuya , Niida Yo , Hasegawa Mitsuhiro , Yamashita Junkoh
Published: June 2005

Cyanotic breath-holding spell is a benign and self-limiting disease of young children but occasionally associated with sudden, unexpected death. The authors report a rare case in a 2-year-old girl with a severe form that started after radical resection of a cervicomedullary ganglioglioma. She was admitted to our hospital because of delayed and unstable gait. Since magnetic resonance imaging showed a cervicomedullary tumor, she underwent a radical resection and histology showed the tumor to be a ganglioglioma. Postoperatively, the function of the lower cranial nerves and cerebellum deteriorated and hemiparesis on the left became apparent, but she returned to the preoperative state in a few months. In addition, mild sleep apnea (Ondine curse) and severe cyanotic breath-holding spells occurred. The former responded to medication but the latter failed and continued several times per day with a rapid onset and progression of hypoxemia, loss of consciousness, sweating and opisthotonos. Five months after the operation, the patient returned home with a portable oxygen saturation monitor equipped with an alarm. This case indicates that cyanotic breath-holding spell, as well as sleep apnea, is critical during the early postoperative period. This is the first report observing that such spells may occur as a complication of radical resection of a cervicomedullary tumor.
An Unusual Presentation of Lumbosacral Dermal Sinus with CSF Leak and Meningitis
Authors: Gupta Deepak K. , Shastank R.R. , Mahapatra A.K.
Published: June 2005

Dermal sinus tracts are common skin manifestations seen with spinal dysraphism. Most of these dermal sinus tracts occur in the lumbosacral region. Though dermal sinus tracts are a common manifestation, their presentation with CSF leak is rare and important as they predispose to recurrent meningitis along with neurological deficits. Here we present an interesting case of a 33-month-old female child with dermal sinus CSF leak, tethered cord and intradural dermoid who presented with meningitis and was treated with excision of the tract, removal of the dermoid and detethering of the cord.
Linezolid for the Treatment of a Heteroresistant Staphylococcus aureus Shunt Infection
Authors: Cook Aaron M. , Ramsey Christian N. , Martin Craig A. , Pittman Thomas
Published: June 2005

The emergence of multidrug-resistant bacteria as the cause of ventriculoperitoneal shunt infections is a disconcerting phenomenon that often requires the use of alternative antimicrobials due to resistance against commonly used agents. The following is a case report describing the successful treatment of a ventriculoperitoneal shunt infection caused by a heteroresistant strain of Staphylococcus aureus with linezolid. Linezolid may have utility in treating pediatric CNS infections due to its tolerability, excellent blood-brain barrier penetration, and activity against multiple resistant Gram-positive organisms such as S. aureus, vancomycin-resistant Enterococcus faecium and Streptococcus pneumoniae.
Non-Cystic-Fibrosis Bronchiectasis in Children: A Persisting Problem in Developing Countries
Authors: Karadag B. , Karakoc F. , Ersu R. , Kut A. , Bakac S. , Dagli E.
Published: June 2005

Background: Non-cystic-fibrosis (non-CF) bronchiectasis in childhood is still one of the most common causes of childhood morbidity in developing countries. The management of these patients remains problematic, and there are few studies of long-term outcome. Objective: The aim of this retrospective study was to define the general characteristics, underlying causative factors and long-term follow-up results of non-CF bronchiectasis patients. Methods: One hundred and eleven consecutive children, diagnosed with non-CF bronchiectasis were included in the study. General characteristics and underlying causes were recorded from the medical records. Clinical outcomes were evaluated in terms of lung function tests, annual exacerbation rates and patient/parent perception of health status. Results: Mean age of the patients was 7.4 ± 3.7 years at presentation, and patients had been followed 4.7 ± 2.7 years on average. In 62.2% of the patients, an underlying etiology was identified, whereas postinfectious bronchiectasis was the most common (29.7%). In spite of intensive medical treatment, 23.4% of the patients required surgery. The annual lower respiratory infection rate has decreased from a mean of 6.6 ± 4.0 to 2.9 ± 2.9 during follow-up (p < 0.0001). Lung function tests were also found to be improved (mean FEV1% 63.3 ± 21.0 vs. 73.9 ± 27.9; p = 0.01; mean FVC% 68.1 ± 22.2 vs. 74.0 ± 24.8; p = 0.04). There was clinical improvement in both the surgical (73%) and medical (70.1%) groups (p > 0.05). Conclusion: In conclusion, bronchiectasis remains a disease of concern to pediatricians, particularly in developing countries. Infections are still important causes of bronchiectasis, and clinical improvement can be achieved by appropriate treatment. Although medical treatment is the mainstay of management, surgery should be considered in selected patients.
Airway Clearance in Bronchiectasis: A Randomized Crossover Trial of Active Cycle of Breathing Techniques versus Acapella®
Authors: Patterson Janet E. , Bradley Judy M. , Hewitt Oonagh , Bradbury Ian , Elborn J. Stuart
Published: June 2005

Background: The efficacy of a new airway clearance device (Acapella®) has not been previously investigated. Active cycle of breathing techniques (ACBT) is the standard airway clearance technique used in patients with bronchiectasis. Objective: The objective of this study was to compare the efficacy of ACBT with Acapella as methods of airway clearance in adults with stable, productive bronchiectasis. Methods: Twenty patients (7 males), age 58 ± 11 years (mean ± SD), FEV1 64 ± 22% predicted with stable (change of not greater than FEV1 10% predicted during 3 months prior to study), productive (history of expectoration of half an egg cup sputum/day) bronchiectasis attended the respiratory clinic on 3 days. Day 1: 40-min training session on ACBT and Acapella. Days 2 and 3: 30-min treatment session of either ACBT or Acapella. Treatment order was determined by a concealed randomization procedure. The following outcomes were measured before and after treatment spirometry, SpO2 and breathlessness by an independent assessor who was blinded to treatment order. Weight of sputum (during treatment plus 30 min after treatment), number of coughs and patient preference were also recorded. Results: No significant differences were found at baseline indicating that patients were stable. No significant differences were found between weight of sputum expectorated with ACBT treatment and weight of sputum expectorated with Acapella treatment – mean difference 0.54 g (95% CI –0.39 to 1.46). A greater proportion of patients preferred Acapella (14/20). Conclusion: Acapella is as effective a method of airway clearance as ACBT and may offer a user-friendly alternative to ACBT for patients with bronchiectasis.
Polymorphisms of B7 (CD80 and CD86) Genes Do Not Affect Disease Susceptibility to Sarcoidosis
Authors: Handa Tomohiro , Nagai Sonoko , Ito Isao , Tabuena Rollin , Shigematsu Michio , Hamada Kunio , Kitaichi Masanori , Izumi Takateru , Aoyama Tomoki , Toguchida Junya , Mishima Michiaki
Published: June 2005

Background: B7 proteins (CD80, CD86) are costimulatory molecules expressed on antigen-presenting cells and are essential factors for T cell activation. Objectives: The aim of this study is to investigate the relationship of B7 gene polymorphisms either to disease susceptibility or to cell profile of bronchoalveolar lavage (BAL) fluid in Japanese sarcoidosis patients. Methods: Gene polymorphisms located in CD80 promoter, CD80 exon 3 and exon 8 of CD86 were examined in 146 Japanese sarcoidosis patients and 157 healthy controls using single-strand conformation polymorphism and direct sequencing. The distribution of genotypes was compared between the two groups. BAL fluid cell profiles were compared for the various genotypes of the different polymorphisms for the 62 patients who underwent BAL. Results: There were no significant differences in the distribution of genotypes or allele frequencies for all polymorphisms between sarcoidosis and controls. There were no significant differences in BAL fluid cell profiles among the different genotype groups of the various polymorphisms studied. Conclusions: There was no relationship between the B7 gene polymorphisms studied and disease susceptibility or BAL fluid cell profiles in Japanese sarcoidosis patients.
Surfactant Protein A Detection in Primary Pulmonary Adenocarcinoma without Bronchioloalveolar Pattern
Authors: Uzaslan Esra , Stuempel Tina , Ebsen Michael , Freudenberg Nikolaus , Nakamura Shinobu , Costabel Ulrich , Guzman Josune
Published: June 2005

Background: Immunohistochemical studies in human lung carcinoma reported positive staining of tumor cells for surfactant protein A (SP-A), especially in peripheral airway cell carcinoma, which include bronchioloalveolar carcinoma and in some reports also papillary subtypes. Objective: The purpose of this study was to determine the SP-A expression in tumor cells of lung adenocarcinoma without a bronchioloalveolar pattern, classified according to the WHO. Methods: In total, 169 primary adenocarcinomas of the lung (109 acinar, 32 solid with mucin, 24 papillary and 4 mucinous) were examined by immunohistochemistry for SP-A expression. Results: Twenty-five percent of acinar, 38% of papillary and 3% of solid adenocarcinoma with mucin showed a positive intracytoplasmic SP-A reaction of the tumor cells. None of the mucinous adenocarcinomas stained for SP-A. This study included the largest number of acinar adenocarcinomas and solid adenocarcinomas with mucin studied for SP-A. We clearly demonstrated that also primary lung adenocarcinoma without a bronchioloalveolar pattern can express SP-A. A positive staining of hyperplastic type II cells surrounding the tumors or entrapped in the tumor could clearly be differentiated from the SP-A-positive stain of tumor cells. Conclusion: These results support the theory that SP-A-producing cells may generate not only bronchioloalveolar and papillary carcinoma, but also other subtypes of lung adenocarcinoma.
Respiratory Syncytial Virus Pneumonitis in Immunocompromised Adults: Clinical Features and Outcome
Authors: Ebbert Jon O. , Limper Andrew H.
Published: June 2005

Background: Though predominantly an infection of children, respiratory syncytial virus (RSV) also infects adults, particularly those with immune compromise. Objectives: To define the clinical spectrum and impact of RSV pneumonitis on hospitalized, immunocompromised adults. Methods: Retrospective chart review. Clinical parameters including premorbid conditions, presentation, radiologic findings, treatment and outcome were examined in a consecutive patients series from an inpatient tertiary-care center.Eleven immunocompromised adults who had undergone bronchoalveolar lavage (BAL) between January 1987 and December 1996 and who had culture-verified RSV pneumonitis were evaluated. Results: This series consisted primarily of patients undergoing chemotherapy or bone marrow transplantation for lymphoma or leukemia. Two were immunosuppressed due to high-dose corticosteroids. A majority (91%) were admitted between November and May, with dyspnea and productive cough. In contrast to earlier studies, there was a paucity of upper respiratory infection symptoms (i.e. sinus congestion, sore throat) and a preponderance of lower respiratory physical exam findings (i.e. wheezing, bibasilar rales). Patients were typically hypoxemic and febrile prior to BAL. Eight demonstrated co-isolates of bacterial or fungi on BAL. The chest radiographs generally revealed diffuse patchy infiltrates, including alveolar opacities. Histology demonstrated diffuse alveolar damage, bronchiolitis with organizing pneumonia, and hyaline membrane formation. Over half required intubation, and 55% died. Although ribavirin therapy may be beneficial in some intubated patients, its overall efficacy cannot be established from this series. Conclusion: RSV is a serious cause of morbidity and mortality in immunocompromised adults. Further development and implementation of an effective vaccine and additional therapeutic interventions are needed.
Impact of Obstructive Sleep Apnea on Right Ventricular Global Function: Sleep Apnea and Myocardial Performance Index
Authors: Dursunoğlu Nese , Dursunoğlu Dursun , Kılıç Mustafa
Published: June 2005

Background: Obstructive sleep apnea (OSA) is characterized by repetitive upper airway obstructions during sleep, and it might cause cardiovascular complications such as heart failure, arrhythmias, myocardial infarction, systemic and pulmonary hypertension. Objectives: To determine right ventricular diameters and myocardial performance index (MPI) reflecting ventricular global function in uncomplicated OSA patients. Methods: 49 subjects without hypertension, diabetes mellitus, or any cardiac or pulmonary disease referred for evaluation of OSA had overnight polysomnography and complete echocardiographic assessment. According to the apnea-hypopnea index (AHI), subjects were divided into three groups: group 1: control subjects (AHI <5, n = 20), group 2: patients with mild OSA (AHI: 5–14, n = 11), and group 3: moderate-severe OSA (AHI ≧15, n = 18). Right ventricular free wall diameter was measured by M mode, and right ventricular MPI was calculated as (isovolumic contraction time + isovolumic relaxation time)/pulmonary ejection time. Results: There were no differences of age, body mass index, heart rates, systolic and diastolic blood pressures among the groups (p > 0.05). Right ventricular end-diastolic and end-systolic diameters were not statistically different between the groups, and were within normal limits. Also, right ventricular free wall diameter was not significantly different between the groups of control, mild OSA and moderate-severe OSA (6.7 ± 0.9, 6.9 ± 1.0, 7.1 ± 1.1 mm, p > 0.05). Right ventricular diastolic dysfunction was shown only in group 3 patients. Right ventricular MPI was statistically higher in group 3 (0.62 ± 0.18) than in group 2 patients (0.50 ± 0.10), and group 1 patients (0.48 ± 0.08, p < 0.001). Conclusions: It wassuggested that patients with moderate-severe OSA had a right ventricular global dysfunction, in addition to the presence of a diastolic dysfunction.
Contraindications and Safety of Transbronchial Lung Biopsy via Flexible Bronchoscopy
Authors: Wahidi Momen M. , Rocha Ana T. , Hollingsworth John W. , Govert Joseph A. , Feller-Kopman David , Ernst Armin
Published: June 2005

Background: Transbronchial lung biopsy (TBLB) via flexible bronchoscopy is a common procedure performed by pulmonologists. Limited scientific data exist concerning the risk of this procedure in patients with conditions that may adversely affect the rate of procedural complications. Objectives: To evaluate the current practice pattern and attitude of pulmonologists toward the performance of TBLB in the presence of high-risk conditions. Methods: A survey was constructed and distributed at the American College of Chest Physicians annual meeting, held in Philadelphia, USA, in November of 2001. Results: A total of 227 surveys were distributed with a return of 158 (69.6%). Anticoagulation medications are temporarily held prior to TBLB by the majority of our survey respondents (98.7% for intravenous heparin, 90.5% for warfarin, and 87.3% for low-molecular-weight heparin). Medications with effect on platelet function are held by fewer pulmonologists. There is a wide variation in the pulmonologists’ perception of the risk of performing TBLB when certain medical conditions coexist: pulmonary hypertension [absolute contraindication (AC), 28.7%; relative contraindication (RC) 58.6%], superior vena cava syndrome (AC 19.6%, RC 51%), mechanical ventilation (AC 17.8%, RC 58.6%) and lung cavity/abscess (AC 7%, RC 44.9%). A significant percentage of pulmonologists (55%) do not regard an elevated serum creatinine at any level as AC to TBLB. Thirty-eight percent of the survey participants administer desmopressin prior to TBLB in uremic patients to prevent excessive bleeding. Conclusions: Prior to performing bronchoscopic TBLB, the majority of pulmonologists temporarily holds anticoagulation medications. However, there is a lack of agreement in relation to perceived contraindications and safety of TBLB.
Penetration of Clarithromycin in Experimental Pleural Empyema Model Fluid
Authors: Liapakis I.E. , Light R.W. , Pitiakoudis M.S. , Karayiannakis A.J. , Giamarellos-Bourboulis E.J. , Ismailos G. , Anagnostoulis S. , Simopoulos C.E. , Bouros D.E.
Published: June 2005

Background: The degree of penetration of clarithromycin into the pleural fluid has not been studied. Objective: To determine the degree to which clarithromycin penetrates into empyemic pleural fluid using a new rabbit model of empyema. Methods: An empyema was created via the intrapleural injection of 1 ml turpentine followed 24 h later by instillation of 5 ml (1010) Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracentesis and pleural fluid analysis, clarithromycin 30 mg/kg was administered intravenously. Antibiotic levels were determined on samples of pleural fluid and blood samples collected serially over 12 h. Antibiotic levels were estimated using HPLC. Results: The antibiotic penetrated well into the empyemic pleural fluid (AUCPF/AUCserum ratio of 1.57). The time to equilibration between the pleural fluid and blood antibiotic levels was 8 h. The peak pleural fluid level (CmaxPF of 2.88 µg/ml) occurred 1 h (TmaxPF of 1 h) after infusion and decreased thereafter. The Cmaxserum was 3.53 µg/ml at 1 h after administration. Conclusion: The levels of clarithromycin in the pleural fluid after intravenous administration are inhibitory for most of the usual pathogens causing empyema. The degree of penetration of clarithromycin should be considered when macrolides are selected for the treatment of patients with empyema.
Long-Term Management of Extensive Tracheal Stenosis due to Formic Acid Chemical Burn
Authors: Stratakos Grigoris , Noppen Marc , Vinken Walter
Published: June 2005

We report on a 26-year-old woman who during early infancy (6 months) suffered from a chemical burn of the skin and upper airways due to spill of formic acid powder. Twenty years after the initial injury, she presented with dyspnea and stridor due to severe tracheal stenosis. Several interventional bronchoscopic manipulations were initiated: incision of the stenotic lesion with Nd:YAG laser and dilatation with a valvuloplasty balloon which enabled silicone stent placement which was subsequently kept in place for 3 years. Complications during the 4th year after stenting led to the successful replacement of this stent by two autoexpandable metallic stents covering the total length of the trachea from the subglottic area to the carina. In post-burn inhalation injuries, a complex inflammatory process may be active for many years after the initial insult. These injuries respond to prolonged tracheal stenting and a conservative approach is recommended.
Association between Neutrophilic and Eosinophilic Inflammation in Patients with Severe Persistent Asthma
Authors: Kikuchi Shinya , Nagata Makoto , Kikuchi Izumi , Hagiwara Koichi , Kanazawa Minoru
Published: June 2005

Background: Eosinophils are generally recognized as effector cells in asthma. Recently, neutrophils have been suggested to contribute to the development of chronic severe asthma. The mechanisms by which neutrophils contribute to the pathophysiology of asthma remain to be elucidated; however, neutrophils may affect either accumulation or functional status of eosinophils via the generation of inflammatory mediators. The objective of this study was to evaluate whether neutrophilic inflammation is associated with eosinophilic inflammation in severe asthma. Methods: Following the inhalation of hypertonic saline, induced sputum was obtained from 12 healthy controls, 10 mild persistent asthmatics who were treated with low-dose inhaled corticosteroids, and 8 severe persistent asthmatics who were treated with combinations of drugs including high-dose inhaled corticosteroids and oral prednisolone. Subsequently, differential inflammatory cell counts were evaluated. Results: The percentage of eosinophils in induced sputum was significantly higher in patients who showed airway neutrophilia. In severe persistent asthmatics, the percentage of neutrophils was significantly correlated with the percentage of eosinophils in induced sputum. Conclusions: The results of the present study suggest that accumulated neutrophils may contribute to the development of eosinophilic inflammation in severe persistent asthmatics who were treated with oral and high-dose inhaled corticosteroids. This effect may contribute to the eventual manifestation of airway inflammation in severe asthma.
RANTES and Eotaxin Enhance CD11b and CD18 Expression on Eosinophils from Allergic Patients with Eosinophilia in the Application of Whole Blood Flow Cytometry Analysis
Authors: Chiba Takahito , Kamada Yumiko , Saito Norihiro , Oyamada Hajime , Ueki Shigeharu , Kobayashi Yoshiki , Kayaba Hiroyuki , Chihara Junichi
Published: June 2005

Background: C-C chemokines and adhesion molecules expressed on eosinophils play an important role in the pathology of allergic inflammatory disease. C-C chemokines such as eotaxin or RANTES are involved in β2 integrin expression on purified eosinophils; so far we have no data on unpurified eosinophils in the peripheral blood. We measured β1 and β2 integrin activation after stimulation with eotaxin or RANTES in vitro using whole-blood flow-cytometric analysis. Methods: Heparinized whole blood obtained from allergic patients with eosinophilia or normal subjects was diluted with the same volume of RPMI 1640, and then cells were incubated in the presence or absence of PMA/ionomycin or chemokines for 45 min at 37°C. After hemolyzation with lysing solution, expression of CD11b, CD11a, CD18 and CD49d on eosinophils was measured using flow cytometry. Results: The expression of CD11b, CD11a and CD18 in allergic patients was significantly higher than that in normal subjects. CD11b and CD18 expression showed a significant increase after stimulation with C-C chemokines, which was remarkable in allergic patients. Conclusion: Eosinophils in the blood of allergic patients exhibited a higher expression of β2 integrins and were more sensitive to RANTES and eotaxin than those of normal subjects.
Leukotriene D4 Induces Production of Transforming Growth Factor-β1 by Eosinophils
Authors: Kato Yoshiko , Fujisawa Takao , Nishimori Hisashi , Katsumata Hajime , Atsuta Jun , Iguchi Kosei , Kamiya Hitoshi
Published: June 2005

Eosinophils may play an important role in the pathogenesis of airway remodeling in asthma through the production of various fibrogenic cytokines such as transforming growth factor-β1 (TGF-β1). Cysteinyl leukotrienes are also suggested to be involved in remodeling with their potential to induce proliferation of airway smooth muscle cells. Since massive eosinophil infiltration and the release of cysteinyl leukotrienes in airway secretions are often seen in asthma, we hypothesized that cysteinyl leukotrienes may be involved in airway remodeling through induction of TGF-β1 from eosinophils. Peripheral blood eosinophils were cultured with leukotriene D4 (LTD4) and/or interleukin-5 (IL-5) or granulocyte colony-stimulating factor (GM-CSF) for 16 h and gene expression of TGF-β1 was quantified with real-time PCR. A combination of LTD4 and IL-5 or LTD4 and GM-CSF synergistically induced TGF-β1 expression in eosinophils although stimulation with single factor, LTD4, IL-5 or GM-CSF did not induce the gene expression. LTD4 also induced significant gene expression in eosinophils cultured in an intercellular adhesion molecule-1-coated plate. The results suggested that CysLTs stimulate eosinophils to induce TGF-β1 production in allergic inflammation where IL-5 and GM-CSF are abundant and may be involved in the pathogenesis of airway remodeling.
The Synthetic Chemoattractant Peptide WKYMVm Induces Superoxide Production by Human Eosinophils via the Phosphoinositide 3-Kinase-Mediated Activation of ERK1/2
Authors: Shin Myeong Heon , Lee Young-Ah , Bae Yoe-Sik , Kita Hirohito , Kim Youngdong , Ryu Sung Ho
Published: June 2005

Background: Eosinophils play a key role in allergic inflammation and parasitic infections. The synthetic peptide, Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), has been previously shown to activate eosinophils and thus to enhance respiratory burst through the formyl peptide receptors. Objective: This study was undertaken to determine the intracellular signaling pathway involved in WKYMVm-stimulated superoxide production by human eosinophils. Methods: Purified eosinophils from peripheral blood were stimulated with various concentrations (10–3 to 10 µM) of WKYMVm and the involvement of PI3-kinase and MAP kinases in WKYMVm-triggered superoxide production was investigated using pharmacological inhibitors. Results: WKYMVm-induced superoxide production by eosinophils was strongly inhibited by pretreatment with the PI3-kinase inhibitor LY294002. In addition, pretreatment with the ERK1/2 kinase inhibitor PD98059 resulted in marked inhibition of superoxide production induced by WKYMVm. Indeed, WKYMVm strongly induced phosphorylation of ERK1/2. The ERK1/2 activation by the peptide was transient and peaked after 2 min of stimulation. Furthermore, ERK1/2 activation by WKYMVm was completely inhibited by pretreatment with the PI3-kinase inhibitor LY294002, but not by the PKC inhibitor Ro-31-8220. Conclusion: These results suggest that WKYMVm stimulates human eosinophils to induce superoxide production via a PI3-kinase-mediated ERK1/2 pathway.
Differential Role of an Atypical Protein Kinase C, PKC ζ, in Regulation of Human Eosinophil and Neutrophil Functions
Authors: Kato Masahiko , Yamaguchi Takafumi , Tachibana Atsushi , Kimura Hirokazu
Published: June 2005

Background: Protein kinase C (PKC) comprises a family of isoenzymes playing a key role in downstream signaling and cell functions. PKCs are grouped according to molecular structure and mode of activation: ‘conventional’ PKCs (α, βI, βII, γ), ‘novel’ PKCs (δ, ε, µ, Θ, η), and ‘atypical’ PKCs (ζ, τ/λ). Here we compared the influence of PKC ζ on the function of human eosinophils and neutrophils. Methods: After pretreating the cells with a myristoylated specific PKC ζ inhibitor, a myristoylated PKC η inhibitor, or bisindolylmaleimide I (Bis I; an inhibitor of conventional and novel PKCs), we examined N-formyl-methionyl-leucyl-phenylalanine (FMLP)- or 4-phorbol 12-myristate 13-acetate (PMA)-evoked superoxide anion (O2–) generation. Induced PKC translocation was characterized using confocal laser scanning microscopy. Results: The PKC ζ inhibitor significantly blocked FMLP- or PMA-induced O2– generation by eosinophils. However, this inhibitor attenuated PMA- but not FMLP-induced O2– generation by neutrophils. In contrast, Bis I inhibited FMLP-induced O2– generation by eosinophils and neutrophils in a similar manner. The PKC η inhibitor had no significant effect, since both cell types lack PKC η; this confirmed specificity of PKC ζ inhibitor effects. Finally, the translocation of PKC ζ to the plasma membrane induced by FMLP in both eosinophils and neutrophils was started at 1 min while the translocation was maintained for 15 min in eosinophils but not in neutrophils. Conclusion: An atypical PKC, PKC ζ, regulates human eosinophil and neutrophil functions in a differential manner.
NR4A Orphan Nuclear Receptor Family in Peripheral Blood Eosinophils from Patients with Atopic Dermatitis and Apoptotic Eosinophils in vitro
Authors: Kagaya Shinji , Hashida Ryoichi , Ohkura Naganari , Tsukada Toshihiko , Sugita Yuji , Terakawa Maki , Tsujimoto Gozoh , Katsunuma Toshio , Akasawa Akira , Matsumoto Kenji , Saito Hirohisa
Published: June 2005

To identify novel genes related to the clinical signs of atopic dermatitis (AD), differentially expressed genes were sought in peripheral blood eosinophils from both AD patients and healthy volunteers. RNA was prepared from eosinophils, expression of various genes was monitored using the Affymetrix GeneChip, and expression was quantified by real-time RT-PCR. Two genes, Nur77 and NOR1, members of NR4A orphan nuclear receptor family, were expressed at a significantly higher level in AD patients than in healthy volunteers. Expression of another gene in the NR4A receptor family, Nurr1, was also higher in AD patients than in healthy volunteers. When peripheral blood leukocytes from healthy volunteers were fractionated, NOR1 expression was highest in eosinophils, but expression of Nur77 and Nurr1 genes was not eosinophil-specific. Extremely intense apoptosis was induced in both eosinophils and an eosinophil cell line, AML14.3D10, by treatment with antibody (Ab) to both CD30 and Fas. Rapid expression of the genes for the NR4A receptor family was observed with anti-CD30 Ab treatment but not with anti-Fas Ab. The NR4A orphan nuclear receptor family gene expression and the subsequent eosinophil apoptosis were downregulated by the MAPK inhibitor, U0126. These results suggest that the expression of the NR4A receptor family genes through CD30 signaling may regulate eosinophil apoptosis in allergic conditions such as AD.
Stat5a Is Essential for the Proliferation and Survival of Murine Mast Cells
Authors: Ikeda Kei , Nakajima Hiroshi , Suzuki Kotaro , Watanabe Norihiko , Kagami Shin-ichiro , Iwamoto Itsuo
Published: June 2005

The regulatory role of signal transducer and activator of transcription (Stat) 5a in the proliferation and survival of mast cells was determined using Stat5a-deficient (Stat5a–/–) mice. First, although the mast cells in Stat5a–/– mice were morphologically indistinguishable from those in wild-type (WT) mice, the number of peritoneal mast cells was significantly decreased in Stat5a–/– mice as compared with that in WT mice. Furthermore, the interleukin-3 (IL-3)-dependent development of bone marrow-derived mast cells (BMMCs) was markedly decreased in Stat5a–/– mice. Second, IL-3-induced but not stem cell factor (SCF)-induced proliferation of BMMCs was significantly diminished in Stat5a–/– mice as compared with that in WT mice. Moreover, survival rates of both peritoneal mast cells and BMMCs were significantly decreased with increased apoptotic cells in Stat5a–/– mice as compared with those in WT mice. Finally, mRNA of Bcl-x(L) was induced after IL-3 stimulation in WT BMMCs but not in Stat5a–/– BMMCs, which may account for the accelerated apoptosis in Stat5a–/– mast cells. These results indicate that Stat5a plays an important role in mast cell development, proliferation, and survival.
Comparison of IL-17 Production by Helper T Cells among Atopic and Nonatopic Asthmatics and Control Subjects
Authors: Hashimoto Tomomi , Akiyama Kazuo , Kobayashi Noriaki , Mori Akio
Published: June 2005

Background: T cells, eosinophils, and neutrophils are strongly involved in the pathogenesis of bronchial asthma. Mechanisms that influence neutrophil accumulation and activation in asthma still remain relatively obscure. There is data indicating that IL-17 is produced by T cells and causes the release of neutrophil-mobilizing cytokines from airway epithelial cells, and that in this way it may regulate airway neutrophilia. Methods: Peripheral blood mononuclear cells (PBMC) obtained from atopic asthmatics (AA), nonatopic asthmatics (NA), and normal control subjects (NC) were stimulated by immobilized anti-CD3 antibody (Ab) plus soluble anti-CD28 Ab or Dermatophagoidesfarinae (Df) extract. Df-reactive T cell clones were established from PBMC of AA and cultured in the presence of various stimulants. The resulting supernatants were assayed for IL-2, IL-4, IL-5, IL-13, IL-17, and IFN-γ by specific ELISAs. Results: PBMC obtained from AA, NA, and NC all produced IL-17 upon immobilized anti-CD3 Ab plus soluble anti-CD28 Ab stimulation. IL-17 production in response to Df extract was significantly induced only in AA. The amount of IL-17 produced by T cell clones stimulated with immobilized anti-CD3 Ab plus soluble anti-CD28 Ab was negatively, but only weakly, correlated with that of IL-4, but not correlated with IL-2, IL-5, IL-13, and IFN-γ production. Conclusion: T cells producing IL-17 in response to Df antigen exist in the peripheral blood of the sensitized AA. IL-17 production might be regulated by unique mechanisms different from those governing Th1 versus Th2 differentiation.
Effects of Corticosteroid on the Expression of Thymus and Activation-Regulated Chemokine in a Murine Model of Allergic Asthma
Authors: Kurokawa Masatsugu , Kokubu Fumio , Matsukura Satoshi , Kawaguchi Mio , Ieki Koushi , Suzuki Shintarou , Odaka Miho , Watanabe Shin , Takeuchi Hiroko , Akabane Tomoko , Asano Kazuhito , Iwase Michiko , Honma Ikuo , Adachi Mitsuru
Published: June 2005

Background: Thymus and activation-regulated chemokine (TARC; CCL17) is a lymphocyte-directed CC chemokine that specifically attracts T-helper (Th) 2 cells positive for the CC chemokine receptor 4 (CCR4+). Corticosteroids reduce airway inflammation, as reflected by reduced numbers of eosinophils and T cells and reduced expression of cytokines. We investigated TARC production and the inhibitory effects of corticosteroids on TARC expression in a murine model of allergic asthma. Methods: BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) with alum. Once daily for 1 week, mice received injections of dexamethasone or 0.2 ml saline (control), then 1 h later inhaled aerosolized 1% OVA for 30 min. Mice were killed 24 h after OVA challenge for bronchoalveolar lavage and lung tissue examination. Results: TARC was expressed mainly in the bronchial epithelial cells. Dexamethasone attenuated OVA-induced airway eosinophilia, lymphocyte infiltration, and airway hyperresponsiveness. Dexamethasone also decreased TARC production in the bronchoalveolar lavage fluid and decreased expression of TARC mRNA and TARC protein in lung tissue. Conclusions: The corticosteroid dexamethasone inhibits TARC production in a murine model of allergic asthma in vivo. The beneficial effect of corticosteroids in bronchial asthma is due in part to their direct inhibitory effects on TARC production.
Infantile Eczema at One Month of Age Is Associated with Cord Blood Eosinophilia and Subsequent Development of Atopic Dermatitis and Wheezing Illness until Two Years of Age
Authors: Matsumoto Kenji , Shimanouchi Yasuhiro , Kawakubo Keiichi , Oishi Naobumi , Wakiguchi Hiroshi , Futamura Kyoko , Saito Hirohisa
Published: June 2005

Background: Physiological and pathological skin eruptions are commonly encountered in neonates in our clinical practice. However, the types of skin eruptions that are associated with the subsequent development of atopic dermatitis and the mechanisms of these associations remain uncertain. Methods: A total of 105 newborn babies with normal delivery were enrolled in this prospective cohort study. The cord blood eosinophil count was measured and the neonates were examined at 1 month of age and followed until 8 years of age. Results: At 1 month of age, infantile eczema, seborrheic dermatitis, intertrigo and diaper dermatitis were diagnosed in a total of 29, 7, 14 and 24 neonates, respectively. No association was found among the prevalences of these eruptions. Neonates with infantile eczema had a significantly higher number and ratio of eosinophils in the cord blood (eosinophil count: 670.8 ± 67.8 vs. 349.0 ± 30.3/µl, p < 0.0001; eosinophil ratio: 5.12 ± 0.53 vs. 2.61 ± 0.22%, p < 0.0001, for the presence and the absence of infantile eczema, respectively). In contrast, no such tendency was found for any other skin eruptions. In neonates with infantile eczema at 1 month of age, the diagnosis of atopic dermatitis had been made significantly earlier and the prevalence of wheezing illness was significantly higher than in those without infantile eczema until 2 years of age. Conclusion: Infantile eczema, but not other skin eruptions, precedes the development of atopic dermatitis and wheezing illness during early infancy, presumably because of the activation of eosinophils before birth.
Evidence and Implications for Multiplicative Interactions among Loci Predisposing to Human Common Disease
Authors: Jones Hywel B. , Faham Malek
Published: June 2005

Objective: The aim of this study was to utilize information on monozygotic twin concordance rates and linkage studies results for common diseases to predict the likely mode of interaction between susceptibility loci. Methods: We calculated combinations of allele frequency and genotypic relative risk (GRR) that would generate linkage results typically observed in common human diseases. Given these single locus effects, we calculated the expected monozygotic twin concordance assuming different numbers of loci under different interaction models. Results: We demonstrate that, for disorders like schizophrenia, a purely additive model of interaction among loci is not consistent with the available evidence. Instead there are likely significant multiplicative or stronger interactions. Given these interactions, we show that in a diagnostic test based on a subset of predisposing loci, the marginal increase of predictive value rises with each additional locus that is discovered. Our model was consistent with susceptibility alleles being common or rare. Conclusions: Evidence from monozygotic twin concordance rates and linkage results point to a significant degree of multiplicative interaction among loci.
Gastric Eosinophilic Granuloma in China: Case Series
Authors: Cao Jiwang , Luo Hesheng , Gao Zhenjun
Published: June 2005

Aim: Eosinophilic granulomas are benign localized lesions in the stomach that are distinct from eosinophilic gastritis. The aim of this study was to identify the potential etiological factors and clinical features of gastric eosinophilic granulomas (GEG). Methods: Clinical manifestations, histopathological features, diagnosis and treatments of 48 hospitalized cases of GEG were analyzed retrospectively. A modified Giemsa staining was employed to detect Helicobacterpylori in 23 of these 48 patients. Results: There was a significant gender difference among patients with GEG with male patients significantly more affected than female patients. The final diagnosis was made after operating the patients (the misdiagnosis level was rather high before resection). Lymphoid follicles were found in 68.6% of the tissues surrounding the lesion. H.pylori infection was detected in 69.6% of patients. In 11 patients eosinophilia in the peripheral blood was observed. Conclusion: The results suggest that H.pylori infection, estrogen status and local allergic reactions may be associated with the development of GEG.
Effect of Acute Hyperglycemia on Intestinal Gas Transit and Tolerance in Nondiabetic Humans
Authors: Harder Hermann , Hernando-Harder Ana C. , Franke Andreas , Krammer Heinz-Juergen , Singer Manfred V.
Published: June 2005

Background: Acute hyperglycemia usually inhibits gastrointestinal motility and hyperinsulinemia may contribute to specific inhibitory effects. However, the influences on postprandial intestinal gas dynamics have not been investigated. Aims: To compare effects of euglycemic hyperinsulinemia and acute fasting hyperglycemia on intestinal gas dynamics in nondiabetics. Methods: On 3 separate days, 10 healthy volunteers were evaluated in randomized order with duodenal glucose, intravenous glucose or saline infusion. Rectal gas evacuation was continuously measured; perception and abdominal girth changes were separately evaluated. After 60 min equilibration, proximal jejunal gas infusion (12 ml/min) was started for 150 min. Results: Acute hyperglycemia failed to cause significant intestinal gas retention (72 ± 64 ml and 53 ± 29 ml final gas retention vs. saline); in contrast, gas clearance was expedited, with a maximal effect between 30 and 105 min (p < 0.001 vs. control). Euglycemic hyperinsulinemia did not significantly influence intestinal gas clearance and no relevant changes of abdominal girth or abdominal and rectal perception were seen, as compared to control (p > 0.05 for all parameters). Conclusion: Accelerated intestinal gas clearance under hyperglycemia is one physiologic factor to avoid postprandial intestinal gas accumulation. Specific underlying mechanisms, which need further investigation, may be disturbed in symptomatic patients.
Pathophysiological Roles of Ectopic Tachygastria Induced with Antral Electrical Stimulation
Authors: Zhu Hongbing , Ouyang Hui , Chen J.D.Z.
Published: June 2005

Aim: To investigate the pathophysiological roles of tachygastria using antral electrical stimulation (AES). Methods: The study was performed on 13 healthy female hound-type dogs chronically implanted with three pairs of serosal electrodes and a gastric cannula (n = 7). In the first experiment (n = 7), the antral motility was measured for three 30-min periods right after a solid meal. AES was performed during the second 30-min period at a tachygastric frequency. In the second experiment (n = 6), gastric slow waves and animal behavior were monitored in the fasting state at baseline and with various parameters of AES. Results: (1) AES at tachygastric frequencies (7–14 cpm) significantly reduced the percentage of normal 4- to 6-cpm slow waves and induced tachygastria; (2) AES significantly and substantially inhibited the antral motility in the fed state; (3) AES in the fasting state energy dependently induced symptoms, and the symptom score was linearly correlated with the stimulation frequency, and (4) there was a significant negative correlation between percentage of tachygastria and index of antral motility. Conclusions: AES induces tachygastria and inhibits the antral motility. Tachygastria is correlated with antral motility.
Relationship of Coffee Consumption with Risk Factors of Atherosclerosis in Rats
Authors: Sakamoto Wataru , Isomura Haruo , Fujie Katsutoshi , Takahashi Kazuhiko , Nakao Kei , Izumi Hiroshi
Published: June 2005

Aims: In experimental animals we investigated the relationship of coffee consumption with risk factors of atherosclerosis such as cholesterol, homocysteine, oxidative stress and inflammatory cytokines. Methods: Forty-eight male Wistar rats were assigned to 3 treatment groups (a control diet group, 0.62% coffee diet group, and 1.36% coffee diet group), and animals were maintained on the experimental diets for 140 days. Results: Coffee diets led to an increase in the caffeine concentration to 0.53 ± 0.11 and 1.77 ± 0.22 µg/ml, respectively, although caffeine in serum was not detected in rats fed the control diet. It also led to slightly increased total serum levels of homocysteine and cholesterol, but no significant differences were found between the control and coffee diet groups. Coffee intake did not affect the production of IL-6 and TNF-α induced by LPS, which contributes to the atheroma-promoting effect of recurrent bacterial infection. Regarding the biomarkers of oxidative stress, the serum level of 15-isoprostane F2t, which was significantly increased by LPS injection, was not altered by coffee intake. In contrast, urinary 8-hydroxy-2-deoxyguanosine was significantly increased in the coffee diet groups (p < 0.05). On the other hand, serum glutathione peroxidase (GPx) activity tended to decrease in the coffee groups compared with the control group, but no significant difference was found between the control and coffee diet groups. Interestingly, a significant negative correlation was observed between GPx activity and homocysteine levels in the sera from control and coffee diet groups (r = –0.403, p < 0.05). Conclusions: This report is the first animal study on the relationship of coffee consumption with risk factors for atherosclerosis. From these results, we conclude that moderate coffee intake is not a risk factor for atherogenesis.
Dietary Caffeine, Performance and Mood: Enhancing and Restorative Effects after Controlling for Withdrawal Reversal
Authors: James Jack E. , Gregg M. Elizabeth , Kane Marian , Harte Frances
Published: June 2005

This study aimed to determine whether sustained (i.e. dietary) use of caffeine has net effects on performance and mood compared with sustained abstinence, and whether dietary caffeine restores performance and mood adversely affected by sleep restriction. Participants (n = 96) alternated weekly between ingesting placebo and caffeine (1.75 mg/kg) three times daily for 4 consecutive weeks, while either rested or sleep restricted. Performance involved either a single task requiring sustained vigilance or a varied battery of brief psychomotor and cognitive tasks, and mood was assessed using the Profile of Mood States. Caffeine had no significant net enhancing effects for either performance or mood when participants were rested, and produced no net restorative effects when performance and mood were degraded by sleep restriction.
Investigating the Effects of Estradiol or Estradiol/Progesterone Treatment on Mood, Depressive Symptoms, Menopausal Symptoms and Subjective Sleep Quality in Older Healthy Hysterectomized Women: A Questionnaire Study
Authors: Heinrich A.B. , Wolf O.T.
Published: June 2005

Clinical studies have documented that estrogen treatment often ameliorates mood disturbances and depressive symptoms occurring during the menopausal transition. The relevance of gonadal hormones for mood and well-being in healthy older nondepressed women is less well understood. Fifty-one healthy hysterectomized women (mean age 64) participated in a placebo-controlled double-blind study on the effects of gonadal hormones on cognition. They received either estradiol (2 mg estradiol valerate), estradiol plus progesterone (100 mg micronized progesterone) or placebo. Mood, well being, menopausal symptoms, depressive symptoms and subjective sleep quality were measured at baseline and after 4 and 24 weeks of treatment using three questionnaires. Thirty-five women could be included into the final analysis. Strong increases in estradiol and progesterone levels occurred in response to the treatment. The two hormones, however, had no effects on mood, well-being, menopausal symptoms, sleep quality and depressive symptoms. The current small study suggests that older healthy nondepressed hysterectomized women do not react with positive or negative mood changes to estradiol or estradiol/progesterone treatment.
Serotonin Dysfunction and Suicide Attempts in Major Depressives: An Auditory Event-Related Potential Study
Authors: Chen Tai-Jui , Yu Younger W.-Y. , Chen Ming-Chao , Wang Shing-Yaw , Tsai Shih-Jen , Lee Tien-Wen
Published: June 2005

Background: Serotonergic dysfunction is believed to be involved in suicide attempts. The loudness-dependent auditory evoked potential (LDAEP) is one of the validated indicators of the activity of the central serotonin system in humans. Objectives: This study was designed to investigate possible differences in the LDAEP and P300 between those depressed patients who attempted suicide and those who did not. Methods: The LDAEP and P300 levels were recorded for 66 depressive patients (among which 16 had attempted suicide). Results: Those who had attempted suicide showed a sharper slope of the LDAEP and increased frontal P300 amplitude. A high correlation between the LDAEP and P300, and a gender difference were also noted. Conclusions: Our results are concordant with previous assumptions about serotonin dysfunction in depressives who attempt suicide.