bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary infection due to Mycobacterium szulgai, case report and review of the literature
Authors: Tortoli E , Besozzi G , Lacchini C , Penati V , Simonetti MT , Emler S
Published: November 2002

We describe the case of a patient with a chronic pulmonary infection due to a mycobacterium tentatively identified as Mycobacterium flavescens, but finally shown to be Mycobacterium szulgai; this is the first M. szulgai infection reported in Italy. The patient responded to treatment with multiple antituberculosis drugs only after two cycles of 10 and 6 months, respectively. The literature concerning previous case reports in which M. szulgai is involved is revised and the difficulty concerning the identification of this rare mycobacterium, along with its in vitro and in vivo susceptibility, are discussed.
Bronchial manifestation of acute febrile neutrophilic dermatosis (Sweet's syndrome)
Authors: Thurnheer R , Stammberger U , Hailemariam S , Russi EW
Published: November 2002

We describe a 62 yr old female with acute febrile neutrophilic dermatosis (AFND) or Sweet's syndrome, involving the bronchial mucosa. The patient presented with classical skin manifestations of AFND accompanied by bilateral pneumonia, pleural effusions and lesions of the oral mucosa. The diagnosis was confirmed by skin and mucosal biopsies. Bronchoscopy revealed raised pustules, similar to the lesions of the skin, suggesting bronchial involvement of AFND. The patient responded to systemic corticosteroids only for a short period and died as a result of multiorgan failure. Postmortem findings confirmed dense, focal neutrophilic infiltrates of the bronchi and bronchioles. No underlying disease was found.
Chlorofluorocarbon-free inhalers: are we ready for the change?
Authors: Partridge MR , Woodcock AA , Sheffer AL , Wanner A , Rubinfeld A
Published: November 2002

Chlorofluorocarbons (CFCs) damage stratospheric ozone permitting enhanced levels of ultraviolet B radiation to reach the Earth's surface. As a result, production of CFCs is now banned under the Montreal Protocol with the exception of their temporary continued use in pressurized metered dose inhalers used to treat those with airway disorders. Replacement propellants have now been identified and shown to be safe and a major exercise is under way to reformulate the commonly used aerosolized medicines with the new propellants. The new products are now undergoing clinical trials and the first reformulated beta-agonist and corticosteroid inhalers have reached the marketplace. The majority of the current products will have been changed over to the new types over the next 3 yrs, and each country will adapt a transition strategy to oversee this process. The politicians, the environmentalists, the pharmaceutical industry and the regulatory authorities have fulfilled their part in this changeover, and respiratory interested health professionals now need to address what this means for them and their patients so that there may be a seamless transition for the millions of people who use inhaled medicines worldwide.
Postoperative lung injury and oxidative damage in patients undergoing pulmonary resection
Authors: Williams EA , Quinlan GJ , Goldstraw P , Gothard JW , Evans TW
Published: November 2002

Postpneumonectomy pulmonary oedema (PPO) complicates a significant number of thoracic surgical procedures involving lung resection and in its extreme form is indistinguishable from the acute respiratory distress syndrome. This study investigated the possibility that ischaemia-reperfusion (I-R) injury contributes to PPO via the production of damaging reactive oxygen species. In a prospective, observational, comparative study, patients undergoing pneumonectomy, lobectomy, or wedge resection or open lung biopsy were investigated for perioperative changes in lung function indicative of lung injury and changes in plasma indices of oxidative damage. Significant percentage perioperative falls in plasma protein thiol levels (-17.9+/-7.0% for pneumonectomy, -24.3+/-5.5% for two-lobe lobectomy and -10.2+/-2.2% for one-lobe lobectomy, p<0.05) and rises in plasma protein carbonyl levels (26.2+/-10.5% for pneumonectomy, p<0.05, 9.8+/-7.0% for two-lobe lobectomy and 5.0+/-2.7% for one-lobe lobectomy) were identified, but not in patients undergoing biopsy or wedge resection. Plasma myeloperoxidase levels rose in all groups, but not significantly. The carbon monoxide transfer coefficient (K(CO)) fell significantly in patients undergoing lobectomy (p<0.05) but not in those undergoing wedge resection, lung biopsy or pneumonectomy. Changes in markers of oxidative protein damage occurred in patients undergoing lung resection, although the gas transfer coefficient fell significantly only following lobectomy. Oxidative damage occurs during pulmonary resection, although associated effects on gas exchange are seen only after lobectomy.
Secretory component production by human bronchial epithelial cells is upregulated by interferon gamma
Authors: Godding V , Sibille Y , Massion PP , Delos M , Sibille C , Thurion P , Giffroy D , Langendries A , Vaerman JP
Published: November 2002

Secretory immunoglobulin A (S-IgA) participates in the first noninflammatory line of defence of the respiratory tract. S-IgA consists of dimeric IgA (dIgA) produced by plasma cells and secretory component (SC) produced by epithelial cells. This study compared SC production by primary cultures of human bronchial epithelial cells (HBEC) and by respiratory epithelial cell lines. Among the cell lines, A549 did not produce detectable SC, 16HBE produced very low levels of SC, while CALU-3 produced significant levels of SC. HBEC produced SC in nonpolarized and polarized primary cultures, where it was secreted apically. Polarized HBEC transcytosed radiolabelled and cold dIgA, resulting in the presence of S-IgA in their apical media. SC production and IgA transcytosis by polarized HBEC were upregulated by interferon-gamma (IFN-gamma) after 48 h. By reverse transcription-polymerase chain reaction, no SC messenger ribonucleic acid (mRNA) was detected in A549 and 16HBE, while SC mRNA in CALU-3 was comparable to that of HBEC incubated for 48 h with IFN-gamma. By immunocytochemistry, HBEC expressed SC immunostaining and its intensity increased after 48 h with IFN-gamma. It is concluded that human bronchial epithelial cells produce secretory component and transcytose dimeric immunoglobulin A in vitro. These processes were apically polarized and upregulated by interferon-gamma. Among the cell lines studied, only CALU-3 expressed secretory component-messenger ribonucleic acid and produced detectable secretory component.
Atopy in cough sensitivity to capsaicin and bronchial responsiveness in young females
Authors: Fujimura M , Kasahara K , Yasui M , Myou S , Ishiura Y , Kamio Y , Hashimoto T , Matsuda T
Published: November 2002

We have shown previously that female sex is a determinant of cough sensitivity to inhaled capsaicin, but the relationship between atopy and the cough sensitivity has not been examined. The capsaicin cough threshold, defined as the lowest concentration of capsaicin causing five or more coughs, nonspecific bronchial responsiveness, defined as the provocative concentration of methacholine causing a 20% fall in the forced expiratory volume in one second (PC20), total immunoglobulin E (IgE) and specific IgEs to eight common aeroallergens (house dust 1, 2 and 6, Dermatophagoides pteronyssinus and D. farinae, Japanese cedar, ragweed and orchard grass) in the serum were measured in 71 nonsmoking, healthy young women aged 20.6+/-0.1 yrs (mean+/-EM). A structured interviewer-led questionnaire on allergic diseases revealed that one and six subjects had mild current and past asthma, respectively. These seven subjects were excluded from the data analysis. PC20 was significantly lower in 42 subjects showing a positive specific IgE than in 22 subjects showing a negative specific IgE to any of the eight allergens (p<0.05), while the capsaicin cough threshold was not significantly different between the subgroups. PC20 was significantly lower in subjects with positive specific IgE to Dermatophagoides and house dust, but not to the three kinds of pollen examined. It was confirmed that atopy indicated by specific immunoglobulin E to mite-related antigens, but not to pollen antigens, is associated with nonspecific bronchial responsiveness, and it is suggested that atopy is not a determinant of airway cough sensitivity in healthy, nonasthmatic subjects.
Attenuation of isocapnic hyperpnoea-induced guinea-pig bronchoconstriction by chronic hypoxia
Authors: Lai YL , Lin CW , Lai LC
Published: November 2002

Chronic hypoxia has been shown to augment the production of antioxidants in rat lungs and to reduce airway hyperreactivity in patients with asthma. This study investigated indirectly whether this increase in antioxidants occurs in guinea-pig lungs and whether the increased antioxidants affect hyperpnoea-induced bronchoconstriction (HIB). Guinea-pigs were divided into four groups: control (n=8); chronic hypoxia (n=7); capsaicin pretreatment (n=7); and capsaicin pretreatment plus chronic hypoxia (n=8). Control animals were not treated. Animals in the hypoxia group were intermittently exposed to an ambient pressure of 380 mmHg for 7 days. A five day pretreatment of capsaicin was used to deplete tachykinins. In the last group, animals were pretreated with capsaicin, followed by a seven day hypoxic exposure. On the day of the study, airway function was examined in the anaesthetized and paralysed animal. Fifteen minutes of hyperpnoea caused marked decreases in the maximal expiratory flow rate at 15% vital capacity, forced expiratory volume in one second, and dynamic respiratory compliance, indicating HIB. This HIB and plasma substance P levels were significantly attenuated by chronic hypoxia, capsaicin pretreatment, and capsaicin pretreatment plus chronic hypoxia. Furthermore, chronic hypoxia attenuated airway constriction induced by xanthine-xanthine oxidase. The results suggest that chronic hypoxia attenuates hyperpnoea-induced bronchoconstriction via a decrease in the oxygen radical-mediated release of tachykinins.
Tolerance to the protective effects of salmeterol on methacholine-induced bronchoconstriction: influence of inhaled corticosteroids
Authors: Boulet LP , Cartier A , Milot J , Cote J , Malo JL , Laviolette M
Published: November 2002

Long-acting beta2-adrenoceptor agonists such as salmeterol reduce airway responsiveness for at least 12 h, but this effect seems to decrease with regular use. We evaluated the time-course of the protective effects of salmeterol on methacholine-induced bronchoconstriction, its modulation by inhaled corticosteroids (ICS) and its influence on asthma control. Thirty two subjects (13 males and 19 females) with mild to moderate stable asthma were divided into two groups according to their medication needs: bronchodilators (BD) alone (n=16) or with ICS (n=16). After a 2 week run-in period, a double-blind crossover study was conducted. Subjects from both groups received salmeterol 50 microg b.i.d. or a placebo for 4 weeks each in random order, separated by a 2 week washout period. The provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) was measured before and after each treatment period, 1 h prior to inhalation of salmeterol or placebo and 1 and 12 h after. Baseline forced expiratory volume in one second (FEV1) increased significantly after salmeterol, both after the first dose and at 4 weeks (BD group: 19 and 17%; ICS: 22 and 13%). On the first day of administration, salmeterol provided significant protection in both groups up to 12 h with a PC20 before and 1 and 12 h postdose of 2.2, 21.7 and 12.4, mg x mL(-1), respectively, in the BD group and 2.1, 11.6 and 55 mg x mL(-1), respectively, in the ICS group. After 4 weeks, this effect was significantly attenuated in both groups with a PC20 before, 1 and 12 h postdose of 3.3, 10.9 and 7.1 mg x mL(-1), respectively, in the BD group and 2.1, 5.0 and 2.3 mg x mL(-1), respectively, in the ICS group. This loss of protective effect was of similar magnitude in both groups. Respiratory symptoms, rescue beta2-agonist use and baseline FEV1 did not change significantly throughout the study in both groups. In conclusion, the bronchoprotective effect of salmeterol decreased with regular use both 1 and 12 h postdose; inhaled corticosteroids did not prevent this reduction. However, the development of tolerance was not associated with loss of asthma control.
Platelet-activating factor increases leukotriene B4 release in stimulated alveolar macrophages from asthmatic patients
Authors: Shindo K , Koide K , Fukumura M
Published: November 2002

This study was designed to examine further the role of platelet-activating factor (PAF) in asthma, comparing leukotriene B4 (LTB4) release, 5-lipoxygenase activity and intracellular calcium levels ([Ca2+]i) in macrophages. LTB4 and other lipoxygenase metabolites in macrophages in bronchoalveolar lavage fluids obtained from 23 asthmatic patients and 20 control subjects were measured by reverse-phase high-performance liquid chromatography. [Ca2+]i was monitored using the fluorescent probe fura-2. The basal LTB4 release of resting macrophages was not different between groups (0.02+/-0.01 versus 0.05+/-0.02 ng x 10(-6) cells). When stimulated with calcium ionophore A23187 (2.5 microM), however, macrophages from asthmatic patients released more LTB4 than cells from control subjects (30.2+/-3.4 versus 13.7+/-2.1 ng x 10(-6) cells). Although PAF alone did not alter LTB4 release, it enhanced the response to subsequent A23187 stimulation. This effect was noted following short treatment (i.e., 5 min) at concentrations of > or =1.0 microM PAF, with the maximal effect noted after treatment with 5.0 microM PAF + 2.5 microM A23187 (105.1+/-6.7 versus 15.3+/-2.6 ng x 10(-6) cells). Treatment of macrophages with PAF also increased 5-lipoxygenase activity and [Ca2+]i more in cytosols from asthmatic patients than in cytosols from control subjects. These findings support a role of intracellular calcium in the activation of 5-lipoxygenase which, in turn, augments the release of leukotriene B4. Because levels of platelet-activating factor may be increased in the lung during asthma and can increase the subsequent release of a chemotactic mediator leukotriene B4, from macrophages, these findings suggest that platelet-activating factor may prime the constitutive cells of the lung to augment inflammatory effects important in the pathogenesis of asthma.
Spectral analysis of wakefulness and REM sleep EEG in patients with sleep apnoea syndrome
Authors: Morisson F , Lavigne G , Petit D , Nielsen T , Malo J , Montplaisir J
Published: November 2002

Neuropsychological investigations of patients with obstructive sleep apnoea syndrome (OSAS) have shown impairments in such basic functions as memory, attention and executive control. Since executive functions are known to be dependent on the integrity of the frontal lobe, it was hypothesized that OSAS may be associated with hypoxaemic frontal lobe dysfunction. To test this hypothesis, 21 apnoeic patients and 10 normal controls were studied with quantitative electroencephalographic (EEG) methods during rapid eye movement (REM) sleep, when most apnoeic events occur and during wakefulness. In apnoeic patients, EEG slowing in REM sleep was observed over frontal, central and parietal regions, while EEG slowing during wakefulness was observed over all cortical regions examined. A positive correlation was found between EEG slowing during wakefulness and oxygen desaturation during the night. Contrary to the hypothesis, these electroencephalographic changes were not localized only to the frontal region. This result may explain the wide range of neuropsychological deficits noted in patients with obstructive sleep apnoea syndrome, in addition to their poor performance in tasks of executive functioning.
Pulmonary vascular disorders in portal hypertension
Authors: Herve P , Lebrec D , Brenot F , Simonneau G , Humbert M , Sitbon O , Duroux P
Published: November 2002

The wide spectrum of pulmonary vascular disorders in liver disease and portal hypertension ranges from the hepatopulmonary syndrome characterized by intrapulmonary vascular dilatations, to pulmonary hypertension (portopulmonary hypertension), in which pulmonary vascular resistance is elevated. Since hepatopulmonary syndrome and portopulmonary hypertension have been reported in patients with nonhepatic portal hypertension, the common factor that determines their development must be portal hypertension. The clinical presentations are very different, with gas exchange impairment in the hepatopulmonary syndrome and haemodynamic failure in portopulmonary hypertension. The severity of hepatopulmonary syndrome seems to parallel the severity of liver failure, whereas no simple relationship has been identified between hepatic impairment and the severity of portopulmonary hypertension. Resolution of hepatopulmonary syndrome is common after liver transplantation, which has an uncertain effect in portopulmonary hypertension. The pathophysiology of both syndromes may involve vasoactive mediators and angiogenic factors.
The role of "fear of corticosteroids" in nonparticipation in early intervention with inhaled corticosteroids in asthma and COPD in general practice
Authors: van Grunsven PM , van Schayck CP , van Kollenburg HJ , van Bosheide K , van den Hoogen HJ , Molema J , van Weel C
Published: November 2002

Treatment of chronic airflow obstruction with inhaled corticosteroids at an early stage has been shown to preserve the lung function. We tested the hypothesis that "fear of corticosteroids" may be an important reason for nonparticipation in the Detection, early Intervention and Monitoring programme on Chronic obstruction pulmonary disease (COPD) and Asthma ("DIMCA") project. One thousand seven hundred and forty nine adult subjects from 10 general practices were invited to participate in the several parts of the "DIMCA" programme. Refusers were questioned about the reason(s) for nonparticipation. Together the screening, monitoring and three drug interventions of the study showed on average 25-35% refusers. The most frequent reasons for nonparticipation were absence of pulmonary symptoms and lack of time. For those invited to take part in one of the three drug interventions, "dislike of medication" was the most important reason for nonparticipation (33, 45 and 67% of the refusers). "Fear of corticosteroids" specifically was the reason for nonparticipation in 8% of the refusers on the basis of "dislike of medication". We concluded that a specific fear of corticosteroids was not a major obstacle for early intervention with inhaled corticosteroids.
Distinct sputum cytokine profiles in cystic fibrosis and other chronic inflammatory airway disease
Authors: Osika E , Cavaillon JM , Chadelat K , Boule M , Fitting C , Tournier G , Clement A
Published: November 2002

The dominant role of inflammation in airways disease progression in cystic fibrosis (CF) is now well established and, based on recent findings, the possibility of an inappropriate inflammatory response in the lung of patients with CF has emerged. In order to characterize this response, the aim of the present work was to evaluate the levels of a number of pro- and anti-inflammatory cytokines in the sputum of CF children and to compare these levels to those observed in the sputum from non-CF children with diffuse bronchiectasis (DB). Three groups of patients were investigated: a group of 25 CF children (mean age: 12.2 yrs), a group of 10 non-CF children with DB (mean age 11.5 yrs), and a group of five healthy young adults (mean age 24 yrs). Elevated concentrations of pro-inflammatory cytokines, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-8 were found in children with CF and in non-CF children with DB, with significantly higher concentrations of IL-1beta in CF children. Analysis of the natural anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) and type II TNF soluble receptor (sTNFRII) concentrations showed distinct patterns, with elevated levels of both inhibitors in CF patients, whereas only sTNFRII was found to be increased in non-CF children with DB. IL-10 data indicated low concentrations in the CF group. In all CF children, the concentrations of IL-6 in the airways were extremely low, independent of the clinical, bacteriological or functional status. By contrast, significantly increased IL-6 levels were found in non-CF children with DB. These results document distinct cytokine profiles in cystic fibrosis patients and noncystic fibrosis patients. They also suggest that impairment of interleukin-6 expression may represent an important component of the excessive inflammatory response observed in cystic fibrosis.
Allergy to laboratory animals in children of parents occupationally exposed to mice, rats and hamsters
Authors: Krakowiak A , Szulc B , Gorski P
Published: November 2002

Sensitization to laboratory animals (LA) has a high prevalence among laboratory workers. It is unknown whether transportation of LA allergens can be a risk factor for sensitization of subjects outside the laboratory environment. The aim of the study was to investigate the prevalence of sensitization to LA among children whose parents were and were not occupationally exposed to LA. The first group consisted of 50 children (age 12.3+/-4.3 yrs) whose parents were occupationally exposed to mice, rats and hamsters. The second group consisted of 40 children (age (mean+/-SD) 10.8+/-3.0 yrs) whose parents were not occupationally exposed to LA. Children having LA at home were eliminated from the study. All children responded to a questionnaire, underwent spirometry and were also tested with skin prick tests with the use of common allergens and prick tests with hair extracts from mouse, hamster and rat. Total immunoglobulin (Ig)E levels and the presence of specific IgE against LA were also estimated. Children of parents occupationally exposed to LA presented significantly more positive skin prick tests against allergens from the hair of laboratory animals compared to children of nonexposed parents. Five children from the first group were also found to have specific IgE against LA, with three of these five children complaining of rhinitis and cough while visiting their parents' workplace. It is concluded that the observed increased sensitization to laboratory animals among children of occupationally exposed parents could be the result of poor hygienic conditions at their parents' workplace. Hence, parents' job seems to be an additional risk factor of sensitization and should be taken into consideration when recording an allergic history.
Expression and localization of cyclo-oxygenase isoforms in non-small cell lung cancer
Authors: Watkins DN , Lenzo JC , Segal A , Garlepp MJ , Thompson PJ
Published: November 2002

The beneficial effects of cyclo-oxygenase (COX) inhibitors in both colon cancer and adenomatous polyps suggest a role for the prostanoid pathway in epithelial malignancy. Although variable prostanoid synthesis in non-small cell lung cancer (NSCLC) has been demonstrated in freshly obtained tissue, COX messenger ribonucleic acid (mRNA) and protein localization in such tumours had not been investigated ex vivo. Thirty-four cases of primary NSCLC were examined for both constitutive (COX-1) and inducible COX (COX-2) by means of in situ hybridization and immunohistochemistry. COX-1 mRNA expression was absent or below the level of detection via in situ hybridization. COX-1 immunohistochemistry demonstrated uniform faint cytoplasmic staining in tumour cells and stromal inflammatory cells. Semiquantitative analysis of COX-2 expression in NSCLC demonstrated the highest levels of both mRNA and protein in adenocarcinoma cells (n=10, p<0.005 compared with large cell and squamous cell carcinoma), intermediate and variable expression in large cell carcinoma (n=11) and low or absent expression in squamous cell tumours (n=13). Levels of COX-2 expression in infiltrating inflammatory cells was the same in all tumour types. In conclusion, tumour cell cyclo-oxygenase-2 rather than cyclo-oxygenase-1 expression may account for the variable prostanoid production seen in non-small cell lung cancer, and primary lung adenocarcinoma expresses the highest levels of cyclooxygenase-2. Assessment of cyclo-oxygenase-2 expression ex vivo should be performed in studies examining the potential therapeutic effects of cyclo-oxygenase inhibitors in non-small cell lung cancer.
Lymphoma of pulmonary mucosa-associated lymphoid tissue: CT scan findings and pathological correlations
Authors: Wislez M , Cadranel J , Antoine M , Milleron B , Bazot M , Mayaud C , Carette MF
Published: November 2002

The aim of this study was to describe the lesions of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma observed by means of computed tomography (CT) and to determine the value of CT in the management of this disease. Sixty six CT scans were performed in 13 consecutive cases of histologically proven pulmonary MALT lymphoma at the time of diagnosis (n=13) or periodically (n=53). They were reviewed separately with chest radiographs by consensus between two observers. Pulmonary abnormalities were described and compared to histopathological findings on surgical specimens from seven patients. At the time of diagnosis, elementary lesions observed by means of CT consisted of nodular areas of attenuation (12 of 13), linear areas of attenuation (eight of 13) and consolidations (six of 13). All these lesions were centred on airways that appeared dilated in seven cases and were more often bilateral and multiple on CT than on the chest radiographs. CT abnormalities correlated with gross pathological appearance and were related to a lymphomatous infiltration with a peribronchovascular distribution. Pathological examination also confirmed the presence of dilated airways within lymphomatous lesions and showed that the bronchial wall was respected. During follow-up, in patients on chemotherapy, response, relapse or progression were easily identified by means of plain radiography. In the initial evaluation, computed tomography contributed to the choice of therapeutic strategy, avoiding unnecessary surgical resection in one-third of patients. By contrast, it is unclear whether computed tomography is useful for post-treatment follow-up of mucosa-associated lymphoid tissue.
Endothelin-1 potentiates cholinergic nerve-mediated contraction in human isolated bronchus
Authors: Fernandes LB , Henry PJ , Goldie RG
Published: November 2002

That endothelin-1(ET-1) plays a mediator role in asthma is consistent with reports of ET-1-induced potentiation of cholinergic nerve-mediated contraction in airways from various animal species. This study examined the effect of ET-1 on cholinergic contractions in human isolated bronchus. Macroscopically nondiseased human bronchial tissue was obtained from 23 patients with respiratory tumours. An electrical field stimulation (EFS) frequency that produced one third of the contraction at 30 Hz (EFS30) was estimated. The effect of ET-1 on these EFS-evoked contractions was assessed. EFS-evoked contractions were frequency-dependent and abolished by either atropine or tetrodotoxin. Thus, EFS-induced contractions were mediated by acetylcholine from cholinergic nerves. ET-1 (3 nM) potentiated EFS-evoked contractions by 10+/-2% EFS30 (p<0.05) without any significant effect on contractions induced by exogenous acetylcholine. Neither the ET(A) receptor-selective antagonist BQ-123 (3 microM) nor the ET(B) receptor-selective antagonist BQ-788 (10 microM) alone significantly altered ET-1-induced potentiation of EFS-evoked contractions. However, in the combined presence of both BQ-123 and BQ-788, ET-1-induced potentiation of EFS-evoked contractions was abolished. Thus, prejunctional endothelinA and endothelinB receptors appear to mediate endothelin-1-induced potentiation of electrical field stimulation-evoked cholinergic contractions in human bronchus. This suggests another potentially important mechanism through which endothelin-1 could increase bronchial tone in asthma.
Left bronchial isomerism, normal atrial arrangement and bronchomalacia mimicking asthma: a new syndrome?
Authors: Bush A
Published: November 2002

Three children who presented with steroid-resistant airflow obstruction are described. They all had bronchomalacia in the setting of a rare visceral arrangement, namely left bronchial isomerism with normal atrial arrangement. Imaging and, in two cases, a normal residual volume in the face of severe airflow obstruction were diagnostic pointers to a nonasthmatic cause of wheeze. Although the association of these abnormalities may be coincidental, together they may constitute a new clinical syndrome.
Developmental immunotoxicology and risk assessment: a workshop summary
Authors: Holsapple M P
Published: November 2002

A workshop entitled ‘Developmental Immunotoxicology and Risk Assessment’ was held on 12–13 June 2001, in Washington, DC. The workshop was organized jointly by the Immunotoxicology Technical Committee (ITC) of the International Life Sciences Institute's (ILSI) Health and Environmental Sciences Institute (HESI) with input from the U.S. Environmental Protection Agency (EPA). Growing public concern that early exposure of the developing immune system to immunotoxic compounds may cause significant or persistent postnatal immunosuppression prompted the workshop. The main goal of the workshop was to examine scientific questions that underlie developmental immunotoxicity tests and the interpretation of the results as they relate to human risk assessment. A second goal was to provide a framework, based on current scientific knowledge, for the development of meaningful testing guidelines. The workshop focused on a series of questions that included how to address critical windows of exposure, how to develop and apply more predictive endpoints, does early chemical exposure cause transient or permanent effects on the immune system, as well as other related questions. On the first day, experts were invited to give scientific presentations relating to comparative developmental immunology, models of immunosuppression, and the regulatory aspects of developmental immunotoxicology. The second day was devoted to a panel discussion that included all the speakers as well as meeting participants, which attempted to answer each of the specific questions raised at the workshop. In general, it was acknowledged that there are a variety of techniques available for assessing immunosuppression in adult animal models, but there is uncertainty about how to apply these to a developing animal, especially if the goal is to have some standard procedure that can be applied for regulatory risk assessment. It was pointed out that although we know a lot about the developing immune system of individual species, we do not know how to relate the significance of drug or chemical effects on these systems in terms of human hazard. Overall, the panel deemed the area of developmental immunotoxicity to be still in its infancy and outlined strategies that could lead to the development of standard practices.
Modification of properties of CaCO3‐polymerization‐filled polyethylene
Authors: Novokshonova L. A. , Meshkova I. N. , Ushakova T. M. , Grinev V. G. , Ladigina T. A. , Gultseva N. M. , Kudinova O. I. , Boer S. De
Published: November 2002

CaCO3–polyethylene (PE) compositions, containing an ultrahigh molecular polyethylene (UHMPE) interlayer between the filler surface and the PE matrix, were synthesized by two‐step polymerization of ethylene on a filler surface activated with a suitable catalyst. The properties of the compositions were studied depending on the molecular weight of the PE matrix and the thickness of the UHMPE intermediate layer at the filler particles. It was shown that the presence of UHMPE as an interlayer in chalk–UHMPE–PE compositions leads to an increase of plastic deformation of the materials as long as the Mw value of the PE matrix is higher than is the brittleness threshold for PE. Chalk–UHMPE–PE compositions exhibit a higher ability for plastic deformation compared to chalk–PE compositions based on a PE matrix of a molecular weight equal to the molecular weight of the total polymer phase (UHMPE–PE) in the first case. There is no improvment of the mechanical properties when the UHMPE is dispersed in the compositions and not as an interlayer between a filler and a matrix. This means that the method of polymerization filling allows one to incorporate the polymer interlayer with a desired nature and properties between a filler surface and polymer matrix in filled polyolefin compositions. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 577–583, 2003
Synthesis and photosensitivity of acryloylmorpholine copolymers with a pendant (meth)acryloyl group
Authors: Ninomiya Atsuyuki , Yoshimura Hikoji
Published: November 2002

We have developed new photopolymers that have superior waterproof properties and that can easily interact with polyfunctional acrylate compounds, thus serving as hydrophobic photocrosslinking reagents. Acryloylmorpholine monomers whose homopolymers were less moisture absorbing than the usual water‐soluble polymers but were still water soluble to a good degree, were copolymerized with other acryloyl monomers. We then introduced the photosensitive (meth)acryloyl group to side chains of the resulting polymers. Among six copolymers examined, the copolymers composed of acryloyl morpholine, hydroxyethyl acrylate, ethyl, or methyl methacrylate, and methacryloyl isocyanate were found to have nicely balanced hydrophilicity and waterproof properties, in addition to good compatibility with hydrophobic photocrosslinking reagents. The composite polymers thus obtained were confirmed to be promising photopolymers usable even in a highly humid environment. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 684–692, 2003
Swelling and drying kinetics of polytetrahydrofuran and polytetrahydrofuran–poly (methyl methacrylate) gels: A photon transmission study
Authors: Yildiz Sevtap , Hepuzer Yeşim , Yağci Yusuf , Pekcan Önder
Published: November 2002

A bifunctional polytetrahydrofuran (PTHF) macromonomer was synthesized by termination of the living polymerization of tetrahydrofuran (THF) initiated by triflic anhydride and the subsequent termination by sodium methacrylate. The PTHF macromonomer thus prepared was polymerized and copolymerized with methyl methacrylate (MMA) by free‐radical polymerization to yield a network and a segmented network of PTHF, both being homogeneous, respectively. These PTHF and PTHF–PMMA gels were used for swelling experiments in chloroform and chloroform vapor. Drying processes were monitored after removing the gels from the solvent and solvent vapor. Photon transmission from PTHF and PTHF–PMMA gels was monitored during swelling and drying processes using a UV‐visible (UVV) spectrophotometer. Transmitted light intensities, Itr, from these gels increased when they were immersed in chloroform and/or subjected to its vapor. The increase in Itr was attributed to the homogeneous lattice structure of PTHF and PTHF–PMMA gels which appeared during swelling. The increase in Itr was modeled using the Li–Tanaka equation from which time constants, τ1, and cooperative diffusion coefficients, DC, were determined. A decrease in Itr after removing choloform and/or its vapor from the cell was observed and attributed to the decrease in homogeneity of lattice structures during drying of the corresponding gels. Time constants, τ2, for the drying processes were also determined. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 632–640, 2003
Effect of hydroxypropyl cellulose in epoxy network formation
Authors: Miranda M. I. G. , Jacobs C. A. B. , Bica C. I. D. , Samios D.
Published: November 2002

Studies on the curing reactions of epoxy systems were carried out in the presence of a cellulose derivative, hydroxypropyl cellulose (HPC). The technique of differential scanning calorimetry (DSC) was applied to characterize the curing reactions/thermal properties. Classical nonisothermal kinetic methods, such as the Kissinger and the Osawa methods (multiple scan) and the Barrett method (single scan) as well as the recently one proposed by Samios et al., were applied to study the reaction kinetics of the epoxy system of diglycidyl ether of bisphenol A (DGEBA) and 4,4′‐diaminodiphenylmethane (DDM) with HPC. The Barrett method gives additional information about the process of initiation, gelation, and vitrification. At the beginning of the epoxy curing reaction, HPC acts as a catalyst so that the energy of activation diminishes and the reaction occurs at lower temperatures. Above the minimum temperature Tmin, it was concluded that HPC behaves as an inhibitor of the reaction (Tmin is the temperature which corresponds to the minimum point showed by the exotermic peaks during the curing reaction of an epoxy resin measured by DSC). By analyzing the behavior of the kinetic parameters, Ea, k, and ln A, the molecular interactions were shown to be related to the catalyst–inhibitor characteristics of HPC. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 676–683, 2003
Role of endogenous regucalcin in nuclear regulation of regenerating rat liver: Suppression of the enhanced ribonucleic acid synthesis activity
Authors: Tsurusaki Yoshinori , Yamaguchi Masayoshi
Published: November 2002

The role of endogenous regucalcin in the regulation of ribonucleic acid (RNA) synthesis activity in the nucleus of normal and regenerating rat livers was investigated. Nuclear RNA synthesis was measured by the incorporation of [3H]‐uridine 5′‐triphosphate into the nuclear RNA in vitro. The presence of regucalcin (0.25 or 0.5 μM) in the reaction mixture caused a significant decrease in nuclear RNA synthesis of normal rat liver. α‐Amanitin (10−8–10−6 M), an inhibitor of RNA polymerase II and III, decreased significantly nuclear RNA synthesis activity. The effect of regucalcin (0.25 μM) in decreasing nuclear RNA synthesis activity was not seen in the presence of α‐amanitin (10−6 M). The calcium chloride (10 μM)‐increased nuclear RNA synthesis activity was significantly suppressed by the addition of regucalcin (0.25 μM). RNA synthesis activity was significantly enhanced in the nuclei of regenating rat liver obtained at 24, 48, or 72 h after partial hepatectomy. This enhancement was significantly inhibited in the presence of PD98059 (10−5 M), staurosporine (10−6 M), or vanadate (10−3 M). Western analysis of the nuclei of regenerating liver obtained at 24, 48, or 72 h after partial hepatectomy showed a significant increase in regucalcin protein as compared with that of sham‐operated rats. The presence of anti‐regucalcin monoclonal antibody (25 or 50 ng/ml) in the reaction mixture caused a significant increase in nuclear RNA synthesis activity of normal rat liver. This increase was completely blocked by the addition of regucalcin (1.0 μM). The effect of anti‐regucalcin monoclonal antibody (50 ng/ml) in increasing nuclear RNA synthesis activity was significantly enhanced in the nuclei of regenerating liver obtained at 24, 48, or 72 h after partial hepatectomy. This enhancement was significantly suppressed by the addition of α‐amanitin (10−6 M), PD98059 (10−5 M), staurosporine (10−6 M), or vanadate (10−3 M) in the reaction mixture. The present study demonstrates that endogenous regucalcin has a suppressive effect on the enhancement of RNA synthesis activity in the nucleus of regenerating rat liver with proliferative cells. J. Cell. Biochem. 87: 450–457, 2002. © 2002 Wiley‐Liss, Inc.
Transcriptional regulation restricting bone sialoprotein gene expression to both hypertrophic chondrocytes and osteoblasts
Authors: Barnes George L. , Torre Thomas Della , Sommer Beatrice , Young Marian F. , Gerstenfeld Louis C.
Published: November 2002

This study identifies a cis‐acting element that confers tissue‐restricted expression to the bone sialoprotein (BSP) gene. Using both gain of function and loss‐of function studies, we demonstrate that this element acts as a tissue specific enhancer of BSP expression in osteoblasts and hypertrophic chondrocytes but does not function in non‐hypertrophic chondrocytes or fibroblasts. Furthermore, our data demonstrate that binding of this element occurs in correlation with active BSP expression. While Dlx5 has been implicated as the tissue‐specific regulator of BSP expression through direct DNA binding at an element with homology to the one under study here, our results demonstrate that Dlx5 does not act as a positive regulator of BSP expression. Finally, mutational analyses of this element demonstrate that while there is homology to putative homeodomain binding elements, this site is unlikely to bind homeodomain factors including Dlx5. Thus, these studies identify an important cis‐acting element in the BSP promoter that acts as a tissue‐specific enhancer of BSP expression in both osteoblasts and hypertrophic chondrocytes. As such this is the first demonstration of a common regulatory mechanism utilized by both chondrocytes and osteoblasts for the tissue‐restricted expression of the BSP gene. J. Cell. Biochem. 87: 458–469, 2002. © 2002 Wiley‐Liss, Inc.
Crystal structures of human antibodies: a detailed and unfinished tapestry of immunoglobulin gene products
Authors: Ramsland Paul A. , Farrugia William
Published: November 2002

Sequencing of all human immunoglobulin (Ig) germline gene segments has recently been completed. However, our first glimpses of the recombined products of this combinatorial gene system were in the 1970s, in landmark publications, reporting the crystal structures of two human myeloma proteins, the Mcg λ light chain dimer and the New IgG1(λ) Fab. Although numerous crystal structures of murine and human antibodies have now been determined, only a relatively small proportion of the human germline genes have had their corresponding protein three‐dimensional structures resolved. Therefore, further structural investigations are required before the inherent diversity of the antibody repertoire can be fully appreciated. We discuss the detailed structural information available for human antibodies with regard to their immune functions. Also discussed, is how the structural information is finding application in the ‘humanization’ of murine antibodies as part of their development as ‘biopharmaceuticals’ for the treatment of human disease. Copyright © 2002 John Wiley & Sons, Ltd.
Mcg in 2030: new techniques for atomic position determination of immune complexes
Authors: Hanson B. Leif , Bunick Gerard J. , Harp Joel M. , Edmundson Allen B.
Published: November 2002

The λ‐type light chain dimer from a patient (Mcg) with multiple myeloma and amyloidosis was a pioneer protein for determining the three‐dimensional structures of immunoglobulins, understanding the effects of ligand binding, and exploring the use of combinatorial methods to identify novel peptides complementary to protein active sites. Despite 30 years of intense study, there are still unanswered questions about the structure of the Mcg dimer, especially with respect to positions of hydrogen atoms and solvent molecules. In the present report, we describe two techniques that will help define the roles of solvent in ligand interactions and complex formation with this immunoglobulin fragment: (1) introduction of helium as a cryogenic agent during X‐ray data collection; and (2) addition of neutron diffraction analyses. These techniques should provide improved resolution, and a more accurate structure of the Mcg dimer. Resolution enhancements of 0.5 Å have been achieved in preliminary experiments with cryogenic helium, as compared with the best X‐ray diffraction data obtained previously. In the near future, neutron diffraction studies should produce the first hydrogen structure for the Mcg dimer and help elucidate the ligand preferences and amyloidogenic properties of this eminently useful protein. Copyright © 2002 John Wiley & Sons, Ltd.
Standard and micro Genetic Algorithm optimization of profiled corrugated horn antennas
Authors: Sinton Seelig , Robinson Jacob , Rahmat‐Samii Yahya
Published: November 2002

The Genetic Algorithm (GA) optimization technique is applied to the optimization of a profiled corrugated horn, designed as a feed for a space‐borne remote sensing reflector‐antenna system. In addition to using the standard GA (SGA) optimization technique, a profiled corrugated horn is also designed and analyzed using micro GA (μGA). A comparative study has been performed among the various designs. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 35: 449–453, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10635
Radiation from a traveling‐wave current sheet at the interface between a conventional material and a metamaterial with negative permittivity and permeability
Authors: Alu Andrea , Engheta Nader
Published: November 2002

In this paper, we present an analysis for the radiation from a traveling‐wave infinitely‐extent sheet of monochromatic electric current that is placed at the interface between a conventional lossless dielectric and a lossless material possessing negative real permittivity and permeability. The field distributions and the direction of the Poynting vectors in both half spaces are discussed, and some physical remarks are provided. A brief note about launching Zenneck waves by a line current along this interface is also mentioned. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 35: 460–463, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10638
Solution of a time‐domain magnetic‐field integral equation for arbitrarily closed conducting bodies using an unconditionally stable methodology
Authors: Chung Young‐seek , Sarkar Tapan K. , Jung Baek Ho
Published: November 2002

In this work, we present a new and efficient numerical method to obtain an unconditionally stable solution for the time‐domain magnetic‐field integral equation (TD‐MFIE) for arbitrarily closed conducting bodies. This novel method does not utilize the customary marching‐on‐in‐time (MOT) solution method often used to solve a hyperbolic partial‐differential equation. Instead, we solve the wave equation by expressing the transient behaviors in terms of weighted Laguerre polynomials. By using these orthonormal basis functions for the temporal variation, the time derivatives in the TD‐MFIE formulation can be handled analytically. Since these weighted Laguerre polynomials converge to zero as time progresses, the electric surface currents also converge to zero when expanded in a series of weighted Laguerre polynomials. In order to solve the wave equation, we introduce two separate testing procedures: spatial and temporal testing. By introducing the temporal testing procedure first, the marching‐on in time procedure is replaced by a recursive relation between the different orders of the weighted Laguerre polynomials. The other novelty of this approach is that through the use of the entire domain Laguerre polynomials for the expansion of the temporal variation of the currents, the spatial and the temporal variables can be separated. To verify our method, we do a comparison with the results of an inverse Fourier transform of a frequency domain MFIE. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 35: 493–499, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10647