bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical phenotypes of COPD: Results of a Japanese epidemiological survey
Authors: TATSUMI Koichiro , KASAHARA Yasunori , KUROSU Katsushi , TANABE Nobuhiro , TAKIGUCHI Yuichi , KURIYAMA Takayuki ,   THE RESPIRATORY FAILURE RESEARCH GROUP IN JAPAN
Published: September 2004

Objective:  The Global Initiative for Obstructive Lung Disease characterizes COPD as airflow limitation caused by parenchymal destruction and/or small airway disease. This report characterizes the clinical features of these two phenotypes of COPD in Japan.

Methodology:  COPD was diagnosed by spirometric airflow limitation (FEV1/FVC < 70%), and all subjects underwent chest CT scanning. Patients with diffuse low attenuation areas (LAA) on CT scan were categorized as the emphysema‐dominant phenotype; those with little LAA were categorized as the airway disease‐dominant phenotype. The two groups were compared to identify significant clinical or demographic differences.

Results:  Of the 1438 patients analysed, 1294 (90%) were classified as having an emphysema‐dominant phenotype and 144 (10%) as having an airway disease‐dominant phenotype. The airway disease‐dominant phenotype was: more common than the emphysema‐dominant phenotype in women (15%vs. 7%, P < 0.01) and in non‐smokers (6%vs. 2%, P < 0.05); was more commonly complicated by asthmatic features (35%vs. 21%, P < 0.01); and had higher IgE and eosinophil levels (P < 0.05) and less lung function impairment.

Conclusion:  This analysis is the first to clinically define two phenotypes of COPD in a Japanese epidemiological survey. There appear to be striking differences as well as overlap between these two groups. Further research is warranted to determine the significance of COPD phenotypes.
Variation in barometric pressure in Melbourne does not significantly affect the BTPS correction factor
Authors: JOHNS David P. , HARTLEY M. Faizel , BURNS Graham , THOMPSON Bruce R.
Published: September 2004

Abstract:  The conventional BTPS (body temperature and pressure, saturated with water vapour) correction factor varies with ambient barometric pressure (PB) and many lung function laboratories measure PB daily. The aim was to investigate whether a fixed value for PB could replace daily measurements. PB was measured daily over a 12‐month period. The highest and lowest values in Melbourne in the last century were also recorded from data published by the Bureau of Meteorology. Using these PB values, the BTPS factor was determined for a range of spirometer temperatures and compared to the BTPS factors obtained using a fixed ambient pressure of 101.3 kPa. The mean (SD) PB measured over the 12‐month period was 102.2 kPa (0.64) with a range of 99.9–103.6 kPa. The level of disagreement between the BTPS factor calculated using a PB of 101.3 kPa instead of the measured value was greater at lower temperatures. Over the extremes of PB during the last century (98.0–104.3 kPa) the use of a standard pressure (101.3 kPa) produced an error in the BTPS factor of ≤ 0.16%. Daily variations in PB do not significantly affect the magnitude of the conventional BTPS correction factor and a fixed value, such as 101.3 kPa at sea level, can be used with little error.
Does addition of inhaled steroid to combined bronchodilator therapy affect health status in patients with COPD?
Authors: YILDIZ Fusun , BASYIGIT Ilknur , YILDIRIM Elif , BOYACI Hasim , ILGAZLI Ahmet
Published: September 2004

Objective:  Withdrawal of corticosteroid is associated with a deterioration of health status in COPD. In this study the aim was to determine whether high dose inhaled corticosteroid improves quality of life in patients with COPD.

Methodology:  In total, 38 male patients with moderate COPD were included in the study. Baseline quality of life scores were determined using a Turkish version of the St George's Respiratory Questionnaire (SGRQ). Patients were randomly divided into two groups. Group 1 consisted of 20 patients who received existing bronchodilator therapy plus inhaled corticosteroid (800 µg budesonide) for 12 weeks, while 18 patients in group 2 received bronchodilator and placebo. The SGRQ was repeated after the treatment period.

Results:  All patients were male and mean age was 67 ± 8.2 years. Symptom, activity, impact, and total scores were assessed and a difference of four units with treatment was considered to be clinically significant. Total score and activity score were decreased by six units and eight units, respectively, in the placebo group while symptom and impact scores did not change significantly. Total scores and the three component scores improved significantly in the corticosteroid group compared to the placebo group (Δtotal score: −22 in corticosteroid group, −6 in placebo group, P < 0.01).

Conclusion:  Inhaled corticosteroid improved quality of life scores in patients with COPD, without significant improvement in airflow obstruction parameters. Since improvement of health status is one of the important aims in COPD treatment, use of inhaled corticosteroids should be considered from this perspective.
Future Perspectives on Employee Selection: Key Directions for Future Research and Practice
Authors: Anderson Neil , Lievens Filip , Van Dam Karen , Ryan Ann Marie
Published: September 2004

Les recherches sur la sélection et l’évaluation sont abordées d’un point de vue tourné vers l’avenir. On recense quatre grand thèmes d’importance majeure dans le développement des futures recherches: la prédiction bimodale, l’adaptation polyvalente, les réactions et décisions pertinentes et les tensions entre la recherche et la pratique dans la sélection professionnelle. Pour chacun de ces thèmes, nous soulevons certains problèmes qui restent à traiter. On discute enfin des conséquences sur la patique et les avancées actuelles dans le domaine de la sélection, traditionnellement l’une des plus actives des disciplines centrales de la psychologie internationales du travail.

A future‐oriented perspective for selection and assessment research is presented. Four superordinate themes of critical import to the development of future research are identified: (i) bimodal prediction, (ii) multilevel fit, (iii) applicant reactions and decision making, and (iv) tensions between research and practice in employee selection. Under each theme we pose a number of outstanding questions for research. Implications for practice and the ongoing advancement of the sub‐field of selection, traditionally one of the most robust core disciplines in international IWO psychology, are discussed.
Evaluating the British Model of Electricity Deregulation
Authors: Thomas Stephen
Published: September 2004

Abstract**:  A key aspect of the 1990 reforms to the British electricity supply industry was the introduction of a formal system of regulation by an autonomous regulatory body. It was expected that replacement of monopolies in some areas by markets and price‐setting in monopoly areas using a simple incentive formula would mean that regulation of the industry would be ‘light’. This article examines how regulation has turned out in practice. It concludes that the promise of ‘light’ regulation has not been fulfilled. Regulation of competitive markets is a major regulatory activity, incentive regulation has evolved into a complex and intrusive form of rate‐of‐return, while regulation of industry structure has allowed the industry to descend into a concentrated, vertically integrated structure, at odds with the aims of the reforms.
Government Underpricing of Share‐Issue Privatizations
Authors: Laurin Claude , Boardman Anthony E. , Vining Aidan R.
Published: September 2004

Abstract***:  The purposes of the paper are to determine whether governments underprice shares in fixed‐price share‐issue privatizations (SIPs) and, if so, what their motivations are for doing so. This paper develops three models of SIP underpricing: one based on revenue goals, one based on political goals and an inclusive model which supposes that the level of underpricing depends on both government revenue goals and political goals. These models are estimated using an international sample of 104 SIPs from 25 countries. We find that, on average, SIPs are underpriced by approximately the same amount as private sector initial public offerings (IPOs). This is not consistent with the sole goal of revenue maximization because SIPs should not require the same degree of underpricing as IPOs. The inclusive regression fits the data well and indicates that both revenue and political goals affect the level of SIP underpricing.
Relational Goods and Associational Participation
Authors: Prouteau Lionel , Wolff François‐Charles
Published: September 2004

Abstract***:  In this paper, we focus on the role of interpersonal contact and the possibility of a relational motive to explain participation and volunteering in associations. Drawing on the relational goods theory, we show that associational activities are favorable to production and consumption of such goods. So, associational participants are expected to have more personal interactions. This theoretical hypothesis is tested using a cross‐sectional data set conducted in France in 1999. Our econometric analysis, which controls for endogeneity of associational participation using a simultaneous equations model, emphasizes a significantly positive relationship between this participation and preferences for relational goods.
What Motivates Members to Participate in Co‐operative and Mutual Businesses?
Authors: Birchall Johnston , Simmons Richard
Published: September 2004

Abstract***: This article reports the findings of a project entitled ‘The participation of members in mutual businesses’. A previous project developed a theoretical model of what makes people participate, focusing on the participation of public service users in council housing and social care services. The current project builds on this work, applying the ‘mutual incentives model’ to a population sample of area committee members and a random sample of non‐participant members of a very large UK consumer co‐operative, the Co‐operative Group. Two arguments are presented as to why such research is needed. First, member participation in co‐operative and mutual businesses is becoming an important issue both for this sector and more generally for public policy. Second, a comparison between a public services setting and a co‐operative setting enables us to extend and further test the theoretical model. Two main features of the model are outlined: a ‘mutual incentives theory’ that goes beyond other models to combine individualistic and collectivistic motivations, and the ‘participation chain’, a synthesis of existing knowledge that joins motivations to three ‘links’ that we call ‘resources’, ‘mobilization’ and ‘dynamics’. The article then summarizes the project methodology, and reports the main findings. As in the public services project, on the ‘demand’ side, collectivistic incentives prove to be dominant over individualistic, but with some individual ‘internal’ benefits also being important. On the ‘supply’ side, skills derived from previous experience were important, as were a positive evaluation of opportunities to participate, and recruitment through existing networks. We then compare the findings to those from the public service users and from a regional co‐operative society; Oxford, Swindon and Gloucester Co‐op. Collective motivations are dominant in all three datasets, but are shown to vary in interesting ways that have important implications for member participation strategies.
Systèmes De Gestion Des Ressources Humaines Et Performance Organisationnelle
Authors: Arcand Michel , Arcand Guy , Bayad Mohamed , Fabi Bruno
Published: September 2004

Résumé**:  La gestion des ressources humaines et son effet sur la performance de la firme représentent encore de nos jours une zone d’indétermination. Plusieurs théories tentent d’ailleurs d’expliquer cette importante relation. C’est l’approche configurationnelle des ressources humaines qui servira de filtre théorique à cette recherche. Validant cette approche auprès de 46 entreprises financières canadiennes, nous avons démontré, en partie du moins, la robustesse de cette approche stratégique de gestion des ressources humaines. Il ne fait aucun doute qu’une telle approche représente une alternative stratégique intéressante, capable d’accroître l’efficacité de nos firmes dans ce monde économique impitoyable et mondialisé.
Exit and/or Voice? Youth and Post‐Communist Citizenship in Bulgaria
Authors: Ådnanes Marian
Published: September 2004

Hirschman's (1970, 1993) theoretical constructs of Exit and Voice represent a useful way to think about citizenship. Exit refers to a desire to emigrate and can be construed as apolitical, private, and passive—a threat to citizenship—whereas Voice refers to political commitment and can be construed as ideal citizenship. A survey of 560 Bulgarian university students in 1998 explored their emphasis on Exit and Voice (as options for themselves in the future) and the association of each option with different economic, political, and psychological factors. One in four students wanted to emigrate, and half of them considered leaving the country for a period of time. Exit plans appeared mainly to be triggered by a wish to participate in the consumer culture, but were also associated with a critical view of the political system as well as a rejection of tradition in conjunction with a Western identity. Although most of the students shared vague or ideal Voice‐related plans, few wanted to become actively involved in politics. An emphasis on Voice reflected not only a somewhat limited political engagement but also a more traditionalistic attitude associated with plans for a career and family. The findings indicate that a normative separation between Exit and Voice as theoretical concepts does not cover the complexities of the Bulgarian students’ emigration and political involvement plans.
FURTHER LESSONS FROM PRIVATISATION
Authors: Ricketts Martin
Published: September 2004

Privatisation transfers assets from state to private ownership. However, this is not a sufficient action for competitive liberal markets to develop. Indeed, attempts by regulators to impose a structure on industries to promote competition actually inhibit the competitive process from determining the most efficient industrial structure. Privatised industries can still have their objectives determined through the political process. Thus, privatisation, to be fully effective, needs to be supported by other policies that will ensure that competition prevails and that the assets of the industries are used to meet the ends of consumers rather than those of politicians.
Flow‐cytometric approach to the prompt laboratory diagnosis of TRALI: a case report
Authors: Porretti Laura , Coluccio Elena , Prati Daniele , Colombo Maria B. , Lopa Raffaella , Tombolini Pietro , Ambrosone Antonella , Crespiatico Loretta , Scalamogna Mario , Rebulla Paolo
Published: September 2004

Abstract:  Objectives: Transfusion‐related acute lung injury (TRALI) is a rare but serious complication which can occur after transfusion of blood components. In this report we describe our flow‐cytometry approach to the laboratory diagnosis of a case of TRALI in a recipient of fresh frozen plasma containing human leukocyte antigen (HLA) class II antibodies. Methods: The post‐transfusion reaction work‐up included the direct and indirect Granulocyte Immunofluorescence Test (GIFT) on the recipient's neutrophils collected before and after the reaction and on the serum from the recipient and from all implicated donors; flow‐cytometry bead‐based screening and identification assay for HLA class I and II antibodies in donor sera and flow cytometry cross‐matching on T and B patient's lymphocytes. Finally, we investigated the reactivity of one donor serum, containing HLA class II antibodies, with the patient's neutrophils activated in vitro to induce expression of HLA class II. Results: We found an increased level of IgG bound on patient's granulocytes collected after TRALI, in the absence of detectable granulocyte and HLA class I antibodies in the five implicated donors. One of them showed HLA‐DR 1 and ‐DR 51 antibodies, which determined a positive cross‐match with patient's B lymphocytes and in vitro activated granulocytes. Both HLA class II antigens were present in the recipient and absent in the donor. Conclusions: In some pathological conditions, HLA class II antibodies can react with activated granulocytes expressing HLA‐DR antigens, and activate TRALI reaction. HLA class II antibodies screening and flow cytometry cross‐matching techniques should be added to the current diagnostic algorithm of TRALI.
Significant thrombocytopenia associated with the addition of rituximab to a combination of fludarabine and cyclophosphamide in the treatment of relapsed follicular lymphoma
Authors: Leo Eugen , Scheuer Lars , Schmidt‐Wolf Ingo G. H. , Kerowgan Mohammed , Schmitt Christina , Leo Albrecht , Baumbach Tanja , Kraemer Alwin , Mey Ulrich , Benner Axel , Parwaresch Reza , Ho Anthony D.
Published: September 2004

Abstract:  Fludarabine in combination with cyclophosphamide is an effective treatment for newly diagnosed as well as relapsed follicular lymphoma. The anti‐CD20 antibody rituximab has been employed successfully for the same indications. No such data were available on a combined use of these agents. Therefore, we conducted a phase II study to evaluate the safety and efficacy of a combination of rituximab (375 mg/m2), fludarabine (4 × 25 mg/m2) and cyclophosphamide (1 × 750 mg/m2), for the treatment of relapsed follicular lymphoma. An unexpected, severe hematologic toxicity with significant, prolonged thrombocytopenias WHO grade III/IV in 6 (35%) of 17 patients treated in total occurred, leading to early termination of the trial. Cytologic and serologic analyses point toward a direct toxic effect. Older patients (mean age 64.7 vs. 56.5 yr) were significantly (P = 0.02) more likely to suffer from this toxicity, whereas no other clinical or hematologic parameter differed statistically between the patients suffering from thrombocytopenia and those who did not. The addition of rituximab to fludarabine/cyclophosphamide employed at doses given above in relapsed follicular lymphoma may have led to this increase in thrombocytopenias. Therefore, caution should be exercised when combining these drugs for the treatment of patients with relapsed follicular lymphoma, especially when treating older patients.
Relation between harvest success and outcome after autologous peripheral blood stem cell transplantation in multiple myeloma
Authors: Wahlin Anders , Eriksson Marie , Hultdin Magnus
Published: September 2004

Abstract:  We studied the prognostic influence of pretransplant characteristics on response and survival in 104 consecutive patients with multiple myeloma receiving uniform pretransplant treatment consisting of VAD regimen, stem cell mobilisation, harvesting, and conditioning with melphalan 200 mg/m2. At the time of peripheral blood stem cell transplantation (PBSCT), 11% of patients were in complete remission (CR), and 63% in partial remission (PR). We evaluated the influence of age, sex, pretransplant response, number of harvested CD34+ cells, number of infused CD34+ cells, splitting part of the harvest for succeeding transplants on overall (OS) and progression‐free survival (PFS) times. Following PBSCT, 31% of the patients were in CR and 57% in PR. Median OS and PFS from transplantation were 67 and 36 months, respectively. Transplant‐related mortality was 0%. The number of harvested CD34+ cells was the only variable that was prognostic for OS in univariate and multivariate analyses. None of the variables was prognostic for PFS, although pretransplant response was nearly significant. The procedure of splitting and saving part of the harvest thus reducing the number of cells in the graft had no influence on outcome measured as OS or PFS.
Anti‐CD20 monoclonal antibody therapy in relapsed MALT lymphoma of the conjunctiva
Authors: Nückel Holger , Meller Daniel , Steuhl Klaus‐Peter , Dührsen Ulrich
Published: September 2004

Abstract:  Low‐grade non‐Hodgkin's lymphomas of the conjunctiva may be cured by radiotherapy, but complications are frequent and relapses may occur. Other treatment modalities including resection, cryotherapy, injection of interferon‐α or systemic chemotherapy have been used with varying success. We treated two patients with relapsed extranodal marginal zone lymphoma (ENMZL) of mucosa‐associated lymphoid tissue (MALT) of the conjunctiva with the anti‐CD20 monoclonal antibody rituximab (375 mg/m2 intravenously once weekly for 4 wk) which has previously been shown to be effective in a variety of other B‐cell non‐Hodgkin's lymphomas. Treatment was well tolerated and resulted in one partial and one complete remission. With a follow‐up of 32 or 30 months, respectively, further recurrences have not been observed. Rituximab is a highly effective and well‐tolerated treatment of conjunctival MALT lymphoma, which may not only be of value in relapse, but also in cases of contraindication to radiotherapy.
Paroxysmal cold haemoglobinuria as a tardive complication of idiopathic myelofibrosis
Authors: Breccia Massimo , D'Elia Gianna Maria , Girelli Gabriella , Vaglio Stefania , Gentilini Fabiana , Chiara Sarlo , Alimena Giuliana
Published: September 2004

Abstract:  Paroxysmal cold haemoglobinuria (PCH) is an autoimmune haemolytic anaemia caused by the Donath–Landsteiner antibody. It is classically described in association with chronic syphilis or after acute viral infections. We describe the first case of PCH presented as a late manifestation of advanced myelofibrosis associated with antiphospholipid syndrome, that promptly responded to high dosage of prednisone.
Combined real time PCR and immunohistochemical evaluation of sperm protein 17 as a cancer‐testis antigen
Authors: Zhang Yana , Wang Zhiqing , Robinson William R. , Lim Seah H.
Published: September 2004

Abstract:  We previously identified sperm protein 17 (Sp17) as a normal testicular protein aberrantly expressed in a proportion of multiple myeloma (MM). However, recent studies have generated controversies on the normal tissue expression of Sp17 and whether or not it is a suitable target for immunotherapy. In this study, we have used a combination of real time polymerase chain reaction and immunohistochemistry on a large panel of normal tissues. Although Sp17 transcripts could be detected in some normal tissues, the levels of expression were <2% of those in normal testis. In contrast, Sp17+ myeloma cells expressed 3–18% of normal testis levels of Sp17 transcript. Immunohistochemistry using two Sp17 murine monoclonal antibodies, each directed at a non‐overlapping B‐cell epitope, showed Sp17 protein to be expressed only in testis and not any other normal tissues. Specificity of binding of the antibodies to testis was also confirmed in competitive binding assays. Our results therefore further suggest Sp17 as a cancer‐testis antigen in MM and support its suitability as a target for immunotherapy.
Differences in the etiology of mandibular fractures in Kuwait, Canada, and Finland
Authors: Oikarinen Kyösti , Schutz Petr , Thalib Lukman , Sándor George K. B. , Clokie Cameron , Meisami Tina , Safar Slavek , Moilanen Mikko , Belal Mohammed
Published: September 2004

Abstract –  We studied causes of mandibular fractures treated in oral and maxillofacial units in three countries in years 1990–2000 in Kuwait (n = 596), 1995–2000 in Canada (n = 228), and 1990–99 in Finland (n = 268). Of the Finnish patients, 27% were women. Corresponding percentages in Kuwait and Canada were 13 and 17%, respectively. Traffic crashes were the cause of injury in 55% of the cases in Kuwait and 33% in Oulu, but only 7% in Toronto. In Kuwait, the victims were often young people, which is why more traffic education, more control of speed, and more control of the use of safety belts should be implemented. Assault was the cause in 54% in Toronto, 12% in Kuwait, and 37% in Oulu. Falling was the cause in 22% of the cases in Kuwait. Alcohol was implicated in 21% of cases in Canada and 15% in Finland.
Multiple complicated crown–root fracture of a permanent incisor
Authors: Turgut Melek D. , Gönül Neslihan , Altay Nil
Published: September 2004

Abstract –  The treatment of a transverse complicated and a vertical uncomplicated crown–root fractures with a horizontal root fracture of a maxillary right central incisor is presented. Coronal fragments were extracted atraumatically and gingivectomy was performed with electrosurgery to expose the subgingival fragment. The root canal was treated with calcium hydroxide to perform the healing at the fracture site. After the root fracture healing, a post was cemented into the canal and the coronal fragment was attached with a composite resin. Examination 18 months after treatment revealed good aesthetics and normal function.
Localized edentulous ridge augmentation with upside down osteotomy prior to implant placement
Authors: Eratalay Kenan , Demiralp Burak , Akıncıbay Hakan , Tözüm Tolga Fikret
Published: September 2004

Abstract –  Localized bone defects may be seen following the extraction of teeth with periapical lesion or advanced periodontal disease, or as a result of trauma. When these regions are considered for treatment with implants, localized ridge augmentation will be necessary. Autogenous bone grafts are used exclusively for ridge augmentation. This case report represents the treatment of a localized edentulous ridge with an upside down osteotomy technique at the symphysis region prior to implant placement. Systemically healthy 21‐year‐old female patient, who was missing a lower right incisor tooth, was scheduled for an implant treatment. However, the crestal width was only 1 mm. The augmentation was planned and the region was treated with an upside down osteotomy technique. Nine months after the augmentation procedure, the computed tomography (CT) examination of the area revealed that the width of the crest was 7 mm, and the height of the crest was in good relation with the cementoenamel junction of the adjacent teeth. Flipping a bone block graft, which was harvested from the edentulous area, upside down may provide a successful result in partially edentulous ridges, in both maxilla and mandible.
Conservative endodontic treatment of teeth fractured in the middle or apical part of the root
Authors: Cvek M. , Mejàre I. , Andreasen J. O.
Published: September 2004

Abstract –  According to treatment type, root‐fractured teeth with pulp necrosis or exposed pulps were divided into five groups, group 1: 17 teeth in which the root canal of the coronal fragment only was filled with gutta‐percha (GP); group 2: seven teeth in which the root canals of the coronal and apical fragments were both filled with GP; group 3: 19 teeth in which the coronal fragment was filled with GP and the apical fragment was surgically removed; group 4: 68 teeth where the root canal of the coronal fragment was treated with calcium hydroxide and subsequently filled with GP; and group 5: five vital teeth with root and concomitant crown fractures in which the exposed pulps were treated by partial pulpotomy. The frequency of periodontal healing was 76% in group 1, zero in group 2, 68% in group 3 and 86% in group 4. Compared with groups 1 and 2 combined, healing in group 4 was significantly more frequent. In groups 1, 2 and 4, failures occurred significantly more often in teeth showing overfilling, i.e. protrusion of GP into the space between the fragments, compared with teeth without overfilling. All five teeth in group 5 showed healing. It was concluded that root canal filling with GP of the coronal fragment only, with or without surgical removal of the apical fragment, can be successful in selected cases. Treatment of the root canal with calcium hydroxide followed by GP filling appears to be the treatment of choice in root‐fractured non‐vital teeth. Partial pulpotomy of exposed pulps in five teeth showed results similar to root‐unfractured teeth with pulp exposure treated with this technique.
Development of clinical and radiographic signs associated with dark discolored primary incisors following traumatic injuries: a prospective controlled study
Authors: Holan Gideon
Published: September 2004

Abstract –  The purpose was to evaluate late complications of asymptomatic traumatized primary incisors with dark coronal discoloration. The clinical and radiographic signs of 97 teeth of the study group were recorded along a follow‐up period that ranged between 12 and 75 months (mean >36 months). Children's age at time of injury ranged between 18 and 72 months (mean 40). The control group consisted of 102 non‐discolored maxillary primary central incisors in 51 children older than 54 months with no history of dental trauma. In 50 teeth (52%) the color faded or became yellowish and in 47 (48%) it remained dark. Clinical signs of infection, that were diagnosed 5–58 months after the injury, were associated significantly more with dark than yellowish hues (83 and 17%, respectively). Teeth that had changed their color to become yellow presented more PCO than teeth with black/gray/brown coronal discoloration (78 and 6%, respectively). Arrest of dentine apposition was found in 15 teeth, one had yellow coronal discoloration and the remaining 14 had a dark shade. Eleven teeth showed inflammatory root resorption all with dark discoloration. Two atypical types of root resorption were observed: a surface resorption restricted to the lateral aspects of the apical half of the root while the root length remained unchanged and in the other expansion of the follicle of the permanent successor was observed. Expansion of the dental follicle was observed in 72% of all teeth with no significant difference between the various types of coronal discoloration but only half of the cases were associated with resorption of the root of the primary incisor. The various pathologic findings observed in the study group were either absent or rarely seen in the control group. It can be concluded that more than 50% of the primary incisors that retain their dark coronal discoloration acquired after dental injuries remain clinically asymptomatic till the eruption of the permanent successor even if they present accelerated root resorption. Asymptomatic traumatized primary incisors that retain their dark coronal discoloration may develop a sinus tract and inflammatory root resorption years after the injury. There is still a dilemma: which treatment is better for dark discolored primary incisors: early endodontic treatment or follow‐up with the risk of development of infection and root resorption that may require extraction?
Reducing chloride conductance prevents hyperkalaemia‐induced loss of twitch force in rat slow‐twitch muscle
Authors: Van Emst Maarten Geert , Klarenbeek Sjoerd , Schot Arend , Plomp Jaap Jan , Doornenbal Arie , Everts Maria Elisabeth
Published: September 2004

Exercise‐induced loss of skeletal muscle K+ can seriously impede muscle performance through membrane depolarization. Thus far, it has been assumed that the negative equilibrium potential and large membrane conductance of Cl− attenuate the loss of force during hyperkalaemia. We questioned this idea because there is some evidence that Cl− itself can exert a depolarizing influence on membrane potential (Vm). With this study we tried to identify the possible roles played by Cl− during hyperkalaemia. Isolated rat soleus muscles were kept at 25 °C and twitch contractions were evoked by current pulses. Reducing [Cl−]o to 5 mm, prior to introducing 12.5 mm Ko, prevented the otherwise occurring loss of force. Reversing the order of introducing these two solutions revealed an additional effect, i.e. the ongoing hyperkalaemia‐related loss of force was sped up tenfold after reducing [Cl−]o. However, hereafter twitch force recovered completely. The recovery of force was absent at [K+]o exceeding 14 mm. In addition, reducing [Cl−]o increased membrane excitability by 24%, as shown by a shift in the relationship between force and current level. Measurements of Vm indicated that the antagonistic effect of reducing [Cl−]o on hyperkalaemia‐induced loss of force was due to low‐Cl−‐induced membrane hyperpolarization. The involvement of specific Cl− conductance was established with 9‐anthracene carboxylic acid (9‐AC). At 100 μm, 9‐AC reduced the loss of force due to hyperkalaemia, while at 200 μm, 9‐AC completely prevented loss of force. To study the role of the Na+−K+−2Cl− cotransporter (NKCC1) in this matter, we added 400 μm of the NKCC inhibitor bumetanide to the incubation medium. This did not affect the hyperkalaemia‐induced loss of force. We conclude that Cl− exerts a permanent depolarizing influence on Vm. This influence of Cl− on Vm, in combination with a large membrane conductance, can apparently have two different effects on hyperkalaemia‐induced loss of force. It might exert a stabilizing influence on force production during short periods of hyperkalaemia, but it can add to the loss of force during prolonged periods of hyperkalaemia.
Transcellular thiocyanate transport by human airway epithelia
Authors: Fragoso Miryam A. , Fernandez Vania , Forteza Rosanna , Randell Scott H. , Salathe Matthias , Conner Gregory E.
Published: September 2004

Human airway mucosa synthesizes and secretes lactoperoxidase (LPO). As H2O2 and thiocyanate (SCN−) are also present, a functional LPO antibacterial defence system exists in the airways. SCN− concentrations in several epithelial secretions are higher than in serum, although the mechanisms of transepithelial transport and accumulation in these secretions are unknown. To examine SCN− accumulation in secretions, human airway epithelial cells, re‐differentiated at the air–liquid interface, were used in open‐circuit conditions. [14C]SCN−, in the basolateral medium, was transported across the epithelium and concentrated tenfold at the apical surface. Measurement of the transepithelial potential showed that the basolateral compartment was positive relative to the apical surface (13.7 ± 1.8 mV) and therefore unfavourable for passive movement of SCN−. Transport was dependent on basolateral [SCN−] and saturable (Km,app= 69 ± 25 μm); was inhibited by increased apical [SCN−]; and was dependent on the presence of basolateral Na+. Perchlorate (Ki,app= 0.6 ± 0.05 μm) and iodide (Ki,app= 9 ± 8 μm) in the basolateral medium reversibly inhibited transport, but furosemide did not. Iodide was also transported (Km,app= 111 ± 69 μm). RT‐PCR and immunohistochemistry confirmed expression of Na+−I− symporter (NIS) in the airways. SCN− transport was insensitive to apical disulphonic acid Cl− channel blockers, but sensitive to apical glibenclamide and arylaminobenzoates. Forskolin and dibutyryl cAMP increased transport. These data suggest SCN− transport may occur through basolateral NIS‐mediated SCN− concentration inside cells, followed by release through an apical channel, perhaps cystic fibrosis transmembrane conductance regulator.
Local protein synthesis and GABAB receptors regulate the reversibility of long‐term potentiation at murine hippocampal mossy fibre–CA3 synapses
Authors: Huang Chiung‐Chun , Hsu Kuei‐Sen
Published: September 2004

Reversal of long‐term potentiation (LTP) by long trains of low‐frequency stimulation is generally referred to as depotentiation. One of the intriguing aspects of depotentiation is that the magnitude of depotentiation is inversely proportional to the time lag of depotentiation stimulation following LTP induction. Although the mechanisms underlying depotentiation have been widely explored, the factors that regulate the susceptibility of LTP to depotentiation stimulation remain largely unclear. We now report that multiple trains of high‐frequency stimulation provide immediate synaptic resistance to depotentiation stimulation at the mossy fibre–CA3 synapses. The synaptic resistance to depotentiation stimulation depends on the amount of synaptic stimulation used to induce LTP; it is prevented by protein synthesis inhibitors and is input specific. In contrast, neither the transection of mossy fibre axons near granule cell somata nor the application of RNA synthesis inhibitors influences synaptic resistance to depotentiation stimulation. We also provide evidence that the induction of depotentiation is regulated by GABAB receptors. Application of a GABAB receptor antagonist significantly promoted the synaptic resistance to depotentiation stimulation, whereas inhibition of GABA transport delayed the onset of this synaptic resistance. These results suggest that local protein synthesis is required for the development of synaptic resistance to depotentiation stimulation, whereas the activation of GABAB receptors promotes the susceptibility to depotentiation stimulation. These two factors may crucially regulate the reversal and stability of long‐term information storage.
Reduced hepatic extraction of palmitate in steatosis correlated to lower level of liver fatty acid binding protein
Authors: Hung Daniel Y. , Siebert Gerhard A. , Chang Ping , Burczynski Frank J. , Roberts Michael S.
Published: September 2004

Nonalcoholic fatty liver disease is the most common of all liver diseases. The hepatic disposition [3H]palmitate and its low-molecular-weight metabolites in perfused normal and steatotic rat liver were studied using the multiple indicator dilution technique and a physiologically based slow diffusion/bound pharmacokinetic model. The steatotic rat model was established by administration of 17α-ethynylestradiol to female Wistar rats. Serum biochemistry markers and histology of treated and normal animals were assessed and indicated the presence of steatosis in the treatment group. The steatotic group showed a significantly higher alanine aminotransferase-to-aspartate aminotransferase ratio, lower levels of liver fatty acid binding protein and cytochrome P-450, as well as microvesicular steatosis with an enlargement of sinusoidal space. Hepatic extraction for unchanged [3H]palmitate and production of low-molecular-weight metabolites were found to be significantly decreased in steatotic animals. Pharmacokinetic analysis suggested that the reduced extraction and sequestration for palmitate and its metabolites was mainly attributed to a reduction in liver fatty acid binding protein in steatosis.
Cytosolic NADPH may regulate differences in basal Nox oxidase-derived superoxide generation in bovine coronary and pulmonary arteries
Authors: Gupte Sachin A. , Kaminski Pawel M. , Floyd Beverly , Agarwal Ritu , Ali Noorjahan , Ahmad Mansoor , Edwards John , Wolin Michael S.
Published: September 2004

Because systems controlled by basal NAD(P)H oxidase activity appear to contribute to differences in responses of endothelium-removed bovine coronary (BCA) and pulmonary (BPA) arteries to hypoxia, we characterized the Nox oxidases activities present in these vascular segments and how cytosolic NAD(P)H redox systems could be controlling oxidase activity. BPA generated ∼60–80% more lucigenin (5 μM) chemiluminescence detectable superoxide than BCA. Apocynin (10 μM), a NAD(P)H oxidase inhibitor, and 6-aminonicotinamide (1 mM), a pentose phosphate inhibitor (PPP), both attenuated (approximately by 50–70%) superoxide detected in BPA and BCA. There was no significant difference in the expression of Nox2 or Nox4 mRNA or protein detected by Western blot analysis. NADPH and NADH increased superoxide in homogenates and isolated microsomal membrane fractions in a manner consistent with BPA and BCA having similar levels of oxidase activity. BPA had 4.2-fold higher levels of NADPH than BCA. The activity and protein levels of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting PPP enzyme generating cytosolic NADPH, were 1.5-fold higher in BPA than BCA. Thus BPA differ from BCA in that they have higher levels of G6PD activity, NADPH, and superoxide. Because both arteries have similar levels of Nox expression and activity, elevated levels of cytosolic NADPH may contribute to increased superoxide in BPA.
Role of hydrogen peroxide in ACh-induced dilation of human submucosal intestinal microvessels
Authors: Hatoum Ossama A. , Binion David G. , Miura Hiroto , Telford Gordon , Otterson Mary F. , Gutterman David D.
Published: September 2004

The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several mediators of vasodilation, which include prostacyclin (PGI2), nitric oxide, and endothelium-derived hyperpolarizing factor (EDHF). We have recently defined the role of nitric oxide and PGI2 in the dilation of submucosal intestinal arterioles from patients with normal bowel function. However, significant endothelium-dependent dilator capacity to ACh remained after inhibiting both these mediators. The current study was designed to examine the potential role of EDHF in human intestinal submucosal arterioles. ACh elicited endothelium-dependent relaxation in the presence of inhibitors of nitric oxide synthase and cyclooxygenase (23 ± 10%, n = 6). This ACh-induced relaxation was inhibited and converted to constriction by catalase (−53 ± 10%, n = 6) or KCl (−30 ± 3%, n = 7), whereas 17-octadecynoic acid and 6-(2-propargylloxyphenyl) hexanoic acid, two inhibitors of cytochrome P450 monooxygenase, had no significant effect (3 ± 1% and 20 ± 8%, n = 5, respectively). Exogenous H2O2 elicited dose-dependent relaxation of intact microvessels (52 ± 10%, n = 7) but caused frank vasoconstriction in arterioles denuded of endothelium (−73 ± 8%, n = 7). ACh markedly increased the dichlorofluorescein fluorescence in intact arterioles in the presence of nitric oxide synthase and cyclooxygenase inhibitors compared with control and compared with catalase-treated microvessels (363.6 ± 49, 218.8 ± 10.6, 221.9 ± 27.9, respectively, P < 0.05 ANOVA, n = 5 arbitrary units). No changes in the dichlorofluorescein fluorescence were recorded in vessels treated with ACh alone. These results indicate that endothelial production of H2O2 occurs in response to ACh in human gut mucosal arterioles but that H2O2 is not an EDHF in this tissue. Rather, we speculate that it stimulates the release of a chemically distinct EDHF.
Distinct cAMP signaling pathways differentially regulate α2C-adrenoceptor expression: role in serum induction in human arteriolar smooth muscle cells
Authors: Chotani Maqsood A. , Mitra Srabani , Eid Ali H. , Han Seon A. , Flavahan Nicholas A.
Published: September 2004

The physiological role of α2-adrenoceptors (α2-ARs) in cutaneous, arteriolar, vascular smooth muscle cells (VSMs) is to mediate cold-induced constriction. In VSMs cultured from human cutaneous arterioles, there is a selective increase in α2C-AR expression after serum stimulation. In the present study, we examined the cellular mechanisms contributing to this response. Serum induction of α2C-ARs was paralleled by increased expression of cyclooxygenase-2 (COX-2), increased release of prostaglandins, and increased intracellular concentration of cAMP. Inhibition of COX-2 by acetyl salicylic acid (1 mM), NS-398 (5 μM), or celecoxib (3 μM) abolished the increase in cAMP and markedly reduced α2C-AR induction in response to serum stimulation. The cAMP agonists, forskolin (10 μM), isoproterenol (10 μM), and cholera toxin (0.1 μg/ml) each dramatically increased expression of α2C-ARs in human cutaneous VSMs. The A-kinase inhibitor H-89 (2 μM) inhibited phosphorylation of cAMP response element binding protein, but not the increase in α2C-AR expression in response to these agonists. cAMP-dependent but A-kinase independent signaling can involve activation of guanine nucleotide exchange factors for the GTP-binding protein, Rap. Indeed, pull-down assays demonstrated Rap1 activation by serum and forskolin in VSM. Transient transfections using α2C-AR promoter-luciferase reporter construct demonstrated that Rap1 increased reporter activity, whereas the A-kinase catalytic subunit decreased reporter activity. These results indicate that cAMP signaling can have dual effects in cutaneous VSMs:activation of α2C-AR transcription mediated by Rap1 GTPase and suppression mediated by A-kinase. The former effect predominates in serum-stimulated VSMs leading to a COX-2, cAMP, and Rap 1-dependent increase in α2C-AR expression. Such increased expression of α2C-ARs may contribute to enhanced cold-induced vasoconstriction and Raynaud's phenomenon.
Decreased epoxygenase and increased epoxide hydrolase expression in the mesenteric artery of obese Zucker rats
Authors: Zhao Xueying , Dey Aparajita , Romanko Olga P. , Stepp David W. , Wang Mong-Heng , Zhou Yiqing , Jin Liming , Pollock Jennifer S. , Webb R. Clinton , Imig John D.
Published: September 2004

Previous studies suggest that epoxyeicosatrienoic acids (EETs) are vasodilators of the mesenteric artery; however, the production and regulation of EETs in the mesenteric artery remain unclear. The present study was designed 1) to determine which epoxygenase isoform may contribute to formation of EETs in mesenteric arteries and 2) to determine the regulation of mesenteric artery cytochrome P-450 (CYP) enzymes in obese Zucker rats. Microvessels were incubated with arachidonic acid, and CYP enzyme activity was determined. Mesenteric arteries demonstrate detectable epoxygenase and hydroxylase activities. Next, protein and mRNA expressions were determined in microvessels. Although renal microvessels express CYP2C23 mRNA and protein, mesenteric arteries lacked CYP2C23 expression. CYP2C11 and CYP2J mRNA and protein were expressed in mesenteric arteries and renal microvessels. In addition, mesenteric artery protein expression was evaluated in lean and obese Zucker rats. Compared with lean Zucker rats, mesenteric arterial CYP2C11 and CYP2J proteins were decreased by 38 and 43%, respectively, in obese Zucker rats. In contrast, soluble epoxide hydrolase mRNA and protein expressions were significantly increased in obese Zucker rat mesenteric arteries. In addition, nitric oxide-independent dilation evoked by acetylcholine was significantly attenuated in mesenteric arteries of obese Zucker rats. These data suggest that the main epoxygenase isoforms expressed in mesenteric arteries are different from those expressed in renal microvessels and that decreased epoxygenases and increased soluble epoxide hydrolase are associated with impaired mesenteric artery dilator function in obese Zucker rats.
Temporal expression profiles of organic anion transport proteins in placenta and fetal liver of the rat
Authors: St-Pierre M. V. , Stallmach T. , Freimoser Grundschober A. , Dufour J.-F. , Serrano M. A. , Marin J. J. G. , Sugiyama Y. , Meier P. J.
Published: September 2004

Physiological cholestasis linked to immature hepatobiliary transport systems for organic anions occurs in rat and human neonates. In utero, the placenta facilitates vectorial transfer of certain fetal-derived solutes to the maternal circulation for elimination. We compared the ontogenesis of organic anion transporters in the placenta and the fetal liver of the rat to assess their relative abundance throughout gestation and to determine whether the placenta compensates for the late maturation of transporters in the developing liver. The mRNA of members of the organic anion transporting polypeptide (Oatp) superfamily, the multidrug resistance protein (Mrp) family, one organic anion transporter (OAT), and the bile acid carriers Na+-taurocholate cotransporting polypeptide (Ntcp) and bile salt export pump (Bsep) was quantified by real-time PCR. The most abundant placental transporters were Oatp4a1, whose mRNA increased 10-fold during gestation, and Mrp1. Mrp1 immunolocalized predominantly to epithelial cells of the endoplacental yolk sac, suggesting an excretory role that sequesters fetal-derived solutes in the yolk sac cavity, and faintly to the basal syncytiotrophoblast surface. The mRNA levels of Oatp2b1, Mrp3, and Bsep in the placenta exceeded those in the fetal liver until day 20 of gestation, suggesting that the fetus relies on placental clearance of substrates when expression in the developing liver is low. Mrp3 immunolocalized to the epithelium of the endoplacental yolk sac and less abundantly in the labyrinth zone and endothelium of the maternal arteries. The placental expression of Oatp1a1, Oatp1a4, Oatp1a5, Oatp1b2, Oat, Ntcp, Mrp2, and Mrp6 was low.