bluuebunny/crossref_metadata_2025_split huggingface dataset:
Picumeterol: dissociation of improvement in lung function and reduction of airways hyperresponsiveness in asthmatics
Authors: Weersink E. J. M. , Postma D. S. , Koëter G. H. , Man Y. , Nials A. T. , Coleman R. A. 
Published: October 2003

Aims The new potent and selective β2‐adrenoceptor agonist, GR 114297A (picumeterol) is the R‐enantiomer of the racemic form, GR 63411B. Picumeterol has been shown to produce long‐lasting relaxation of airways smooth muscle both in vitro and in vivo. We assessed the intrinsic activity of picumeterol by increasing intracellular levels of c‐AMP and compared this with isoprenaline and salbutamol. Methods In human atopic asthmatics, we have investigated the duration of action and efficacy of picumeterol and GR 63411B with regard to improvement in resting lung function (i.e. FEV1 ) and airways responsiveness (i.e. PC20 ) to methacholine (MCh). The study design consists of two clinical parts each for one drug. Different asthmatics participated in the two studies, seven in the first part and eight in the second part. In human bronchial smooth muscle cells in vitro, we have investigated the intrinsic activity of picumeterol in increasing intracellular levels of cyclic AMP and compared it with isoprenaline and salbutamol. Results In vivo, both drugs caused bronchodilatation with similar potency, but, their effects were short‐lasting. Despite their bronchodilator activity, neither drug improved PC20, when compared with placebo. In vitro, picumeterol was found have intrinsic activity lower than the other β2‐adrenoceptor agonists tested. Conclusions In the clinical studies, the bronchodilator potencies of picumeterol and GR 63411B were similar. However, both drugs were short‐acting, which is at odds with their activity in vitro. Our data suggest that these compounds display dissociation between bronchodilator activity and protection against MCh‐induced bronchoconstriction. These findings may be explained by low intrinsic activity and need further conformation.
Comparison of nitroprusside and nitroglycerin in inhibition of angiotensin II and other vasoconstrictor‐mediated contraction in human coronary bypass conduits
Authors: Guo‐Wei He  , Yang Cheng‐Qin 
Published: October 2003

Aims To compare the effect of nitroprusside (SNP) and nitroglycerin (NTG) on angiotensin II (ANGII), endothelin‐1 (ET‐1), and &agr;1‐adrenoceptor (phenylephrine, PE)‐mediated contraction in internal mammary artery (IMA). Methods Human IMA segments (n=120) taken from 37 patients were studied. Concentration‐relaxation curves for SNP and NTG were established in IMA precontracted with these vasoconstrictors. Concentration‐contraction curves were also constructed in IMA rings incubated with SNP and NTG (0.1 and 1 &mgr;m ) for 10 min. Results Both SNP and NTG caused full relaxation with similar EC50 s except NTG was four‐fold more potent than SNP in PE‐induced contraction (−7.92±0.06 vs−7.32±0.2 log m, mean±s.e. mean, P<0.01; 95% confidence interval for the difference of the means: 0.19, 1.01 log m ). Pretreatment with SNP (0.1 and 1 &mgr;m ) significantly depressed the contraction by ANGII from 56.6±7.7% (of 100 mm K+‐contraction) to 18.3±8.6% and 3.9±2.1% (P=0.0001). In four rings treated with SNP, the contraction to ANGII was abolished whereas NTG did not depress ANGII‐mediated contraction. Pretreatment with SNP (1 &mgr;m ), but not NTG, significantly depressed the magnitude of the PE‐induced contraction from 4.7±1.2 to 1.7±0.4 g (P<0.05). Treatment with both SNP and NTG significantly increased the EC50 (−5.09±0.17 log m, P=0.0007 for SNP and −5.40±0.06 log M, P=0.02 for NTG). Pretreatment with SNP did not significantly change either the magnitude or the EC50 of the ET‐1‐induced contraction. Conclusions SNP may be advantageous compared with NTG in preventing coronary arterial graft contraction. However, once grafts have constricted to ANGII, &agr;1‐adrenoceptor agonists, and ET‐1, NTG may be only marginally advantageous.
The GIMEMA ALL 0183 trial: analysis of 10‐year follow‐up
Authors: Mandelli Franco , Annino Luciana , Rotoli Bruno 
Published: October 2003

We report the 10‐year follow‐up of the GIMEMA ALL 0183 trial.From 1983 to 1987, 358 adults with acute lymphoblastic leukaemia (ALL) were entered into this trial, which included a mild induction, an early intensive consolidation, a post‐consolidation phase randomized in conventional maintenance (arm A) and in more intensive regimen (arm B). CNS prophylaxis did not include CNS irradiation. The overall complete remission (CR) rate was 79.3% (284/358); 212 patients were randomized (110 in arm A and 102 in arm B).The median overall CR duration was 20 months and the median overall survival (OS) 21 months; both curves reach a plateau after 6 years; at 10 years 25% of patients were projected to be in long‐term remission and survivors. The median disease‐free survival (DFS) was 17 months, at 10 years 27% and 28% of patients were DFSs in arm A and in arm B respectively.In multivariate analysis age, WBC count and L2 FAB subtype were found to significantly influence OS and DFS. With regard to our previous report OS appears to linearly correlate with initial WBC count and age (P=0.0002 and P=0.042 respectively).195 (68.7%) patients relapsed (only 25 had isolated CNS). The overall second CR rate was 56.5%; 23 patients underwent transplantation (12 BMT and 11 ABMT). Post‐relapse survival was found to be influenced by the duration of first CR.
Allogeneic marrow transplantation for aplastic anaemia associated with dyskeratosis congenita
Authors: Langston Amelia A. , Sanders Jean E. , Deeg H. Joachim , Crawford Stephen W. , Anasetti Claudio , Sullivan Keith M. , Flowers Mary E. D. , Storb Rainer 
Published: October 2003

Eight patients with aplastic anaemia associated with dyskeratosis congenita received allogeneic marrow grafts from either HLA‐identical siblings (six patients) or HLA‐matched unrelated donors (two patients). Patients who received marrow from HLA‐identical siblings were conditioned with cyclophosphamide (140–200 mg/kg), with or without antithymocyte globulin. Patients who received unrelated donor marrow were conditioned with cyclophosphamide (120 mg/kg) and total body irradiation (1200 cGy). The six patients who survived for >2 weeks following transplant all had haematological evidence of engraftment, and all three patients who survived for at least a year following transplant recovered normal haematological function. Three patients died with respiratory failure and pulmonary fibrosis at 70 d, 8 years and 20 years post‐transplant; three patients died during the neutropenic period of invasive fungal infections; one patient died on day 44 of refractory acute graft‐versus‐host disease; and one patient remains alive 463 d following transplant. The surviving patient recently underwent surgical resection of a Dukes' stage C rectal carcinoma diagnosed 14 months post‐transplant.The aplastic anaemia associated with dyskeratosis congenita can be successfully treated by allogeneic bone marrow transplantation; however, this approach does not reverse the other systemic manifestations of the syndrome. The pathogenesis of the interstitial lung disease observed in dyskeratosis congenita patients following marrow transplantation is not understood.
Comparison of cell proliferation in the centre and advancing fronts of oral squamous cell carcinomas using Ki‐67 index
Authors: Dissanayake U. , Johnson N. W. , Warnakulasuriya K. A. A. S. 
Published: October 2003

Abstract.  The cell proliferation status of 60 oral squamous cell carcinomas from Sri Lankan subjects was examined by immunohistochemistry using the Ki‐67 index. A comparison was made between the indices derived from the centre of the tumours and those derived from the invasive fronts of the same tumours. There was a positive correlation between the two indices suggesting a clonal expansion of malignant cells, but the mean index derived for the invasive fronts (29.75 11.64) was significantly higher than the mean index for the body of these tumours (25.65 11.64). Thus, at a given time, more peripheral cells at the invasive front are proliferating and this compartment is likely to be more informative in prognostic and other behavioural studies involving the cell cycle. In squamous carcinomas, increased and uncontrolled cell proliferation at the invasive front may be one feature contributory to the invasion.
Expression of intercellular adhesion molecules on circulating lymphocytes in relation to different manifestations of cow's milk allergy
Authors: Österlund P. , Smedberg T. , Schröder J. , Järvinen K.‐M. 
Published: October 2003

SummaryBackgroundThe complex interactions between immune cells are partly mediated by different adhesion molecules, but little is known about their role in the systemic immunoinflammatory process following sensitization to food antigens in early infancy.ObjectiveThe aim of this study was to investigate the expression of intercellular adhesion molecule‐1 (ICAM‐1or CD54) and the α subunits of its ligands' lymphocyte function‐associated antigen‐1 (LFA‐1) (αLsubunit or CD11a) and Mac‐1 (αMsubunit or CD11b) on peripheral blood leucocytes in infants with cow's milk allergy (CMA) and in healthy controls.MethodsThirty‐nine breastfed infants, aged from 0.6 to 8.3 months, and their lactating mothers were included in the study from delivery onwards. During follow‐up, 25 infants developed CMA and 14 remained healthy. Expressions of CD54 and CD11b on peripheral blood leucocytes were evaluated by flow cytometry. In addition, the expression of CD11a on peripheral blood leucocytes was analysed by immunocytochemistry. Mothers' milk samples were collected and their leucocyte content was evaluated using a light microscope.ResultsThe frequency of ICAM‐1 expressing peripheral blood lymphocytes was significantly higher in patients with CMA than in healthy infants (P=0.03, Mann–WhitneyU‐test). Furthermore, the high proportion of ICAM‐1‐expressing cells was associated with gastrointestinal and multiorgan symptoms in the CMA infants. There was no significant difference in the expression of Mac‐1 αMon lymphocytes in our study groups, but the LFA‐1 αLexpression seemed to be higher in the IgE‐mediated CMA.ConclusionWe suggest that the high expression of ICAM‐1 on peripheral blood lymphocytes may reflect enhanced stimulation of T cellsin vivoand their migration to the effector tissues in an early‐phase of developing CMA. Furthermore, high ICAM‐1 expression may be associated with the presence of multiorgan manifestations of CMA, whereas high LFA‐1 expression may reflect the IgE‐mediated disease.
A rapid microbiopsy system to improve the preservation of biological samples prior to high‐pressure freezing
Authors: Vanhecke D. , Graber W. , Herrmann G. , Al‐Amoudi A. , Eggli P. , Studer D. 
Published: October 2003

SummaryA microbiopsy system for fast excision and transfer of biological specimens from donor to high‐pressure freezer was developed. With a modified, commercially available, Promag 1.2 biopsy gun, tissue samples can be excised with a size small enough (0.6 mm × 1.2 mm × 0.3 mm) to be easily transferred into a newly designed specimen platelet. A self‐made transfer unit allows fast transfer of the specimen from the needle into the specimen platelet. The platelet is then fixed in a commercially available specimen holder of a high‐pressure freezing machine (EM PACT, Leica Microsystems, Vienna, Austria) and frozen therein. The time required by a well‐instructed (but not experienced) person to execute all steps is in the range of half a minute. This period is considered short enough to maintain the excised tissue pieces close to their native state. We show that a range of animal tissues (liver, brain, kidney and muscle) are well preserved. To prove the quality of freezing achieved with the system, we show vitrified ivy leaves high‐pressure frozen in the new specimen platelet.
An oscillating cryo‐knife reduces cutting‐induced deformation of vitreous ultrathin sections
Authors: Al‐Amoudi A. , Dubochet J. , Gnaegi H. , Lüthi W. , Studer D. 
Published: October 2003

SummaryA new oscillating cryo‐knife for producing uncompressed vitreous sections is introduced. The knife is a modified cryo diamond knife that is driven by a piezo translator. Optimal setting for the oscillation was found to be in the inaudible frequency range of 20–25 kHz. Yeast cells and polystyrene spheres were used as model systems to describe compression in the vitreous sections. We found that compression could be reduced by a factor of about 2 when the knife was oscillating. When the oscillator was turned off, sections were compressed by 40–45%. However, only 15–25% compression was obtained when the knife was oscillating. In some cases completely uncompressed sections of yeast cells were produced. It was also found that the amount of compression depends on the specimen itself and on its embedding medium. With the results shown here, we demonstrate that the oscillating knife can produce high‐quality vitreous sections with minimum cutting artefacts.
Influence of maternal infection on offspring immune response in murine larval toxocariasis
Authors: Reiterová K. , Tomašovicová O. , Dubinský P. 
Published: October 2003

SUMMARYThe impact of Toxocara canis infection on the proportion of CD4+ and CD8+ T splenocytes, the serum concentrations of cytokine IFN‐γ and IL‐5, and the production of Toxocara‐specific antibodies were studied in two C57BL6/J mouse groups and their offspring. The mice were infected with 1000 T. canis eggs on the day of mating (early infection) and on day 14 of pregnancy (late infection). Early infection resulted in a significant increase of CD4+ T‐cell subtype, however, a decline in CD8+ in comparison with late infection, as well as with non‐infected control. The IFN‐γ serum concentrations decreased in infected mothers after the birth when compared with non‐infected mothers, while in the offspring this cytokine was barely or not detectable. In the mothers of both infected groups, the humoral immune response included both parasite‐specific IgM and IgG2 antibodies. While IgG1 levels remained constant throughout the whole experiment in mothers with early infection, late‐infected mothers became seropositive only 3 weeks after delivery. IgM was not detectable in any offspring. Pups from early‐infected mothers had IgG1 antibodies. Conversely, IgG2 was detectable in pups of both experimental infection groups. A significant difference was observed in the amounts of pups/litter of the infected mothers in comparison with the non‐infected ones. Only 56% of females after early infection and 79% of those after late infection had a successful pregnancy. However, all mice of the control group produced a litter. The first T. canis larvae were detected in the muscles of the offspring of both groups on day 5 after the birth. These data show the changes in regulatory and cytotoxic immunity mechanisms of the infected mothers and their offspring and the high level of pregnancy loss as a result of larval toxocariasis.
Cytokine gene expression in dams and foetuses after experimentalNeospora caninuminfection of heifers at 110 days of gestation
Authors: Almeria S. , De Marez T. , Dawson H. , Araujo R. , Dubey J. P. , Gasbarre L. C. 
Published: October 2003

SUMMARYNeospora caninumis a major cause of abortion in cattle. An essential role for Th1 cytokines, such as IFN‐gamma and IL‐12 in protective immunity againstN. caninumin murine models has been indicated. However, little is known about immunity toNeosporain pregnant cattle where a considerable level of immunomodulation may exist. In this study, the immune response of heifers infected early in the second trimester of pregnancy by intravenous inoculation ofN. caninumtachyzoites was compared with immune responses in uninfected pregnant heifers. Animals were killed 3 weeks after infection. No abortion was observed in any infected dam, however, transplacental infection was shown to have already taken place. Infection withN. caninumduring pregnancy induced significant immune responses in both dams and their foetuses. Infected dams showed significant changes in lymphocyte subpopulations compared with uninfected pregnant animals and these changes were compartmentalized. Increased levels of T lymphocytes were observed in the infected foetuses. Cytokine gene expression analysed by real time RT‐PCR showed increased expression of both Th1 and Th2 cytokines inN. caninuminfected animals. This cytokine expression could have a role in the transplacental transmission of the parasite and/or mediate tissue damage.
Rare variants of Cutaneous Leishmaniasis: Whitlow, paronychia, and sporotrichoid
Authors: Iftikhar Nadia , Bari Irfan , Ejaz Amer 
Published: October 2003

AbstractCutaneous Leishmaniasis is endemic in certain areas of Pakistan, with the wet form of the disease being the most prevalent. It has a number of morphological variants, which are dependant on the immune status of the host, the subspecies of the Leishmania, and also, to some extent, on the site of involvement. We describe here a case of Leishmaniasis showing two very rare variants, whitlow and paronychial lesions, occurring concurrently with sporotrichoid spread. The patient responded to intramuscular sodium stibogluconate with resolution of the skin lesions.
Diagnostic performance and retention of acquired skills after dermatology elective
Authors: Enk Claes D. , Gilead Leon , Smolovich Irena , Cohen Robert 
Published: October 2003

AbstractBackground   The dermatology elective often constitutes the future physician's only exposure to dermatologic practice. Cost–benefit considerations dictate that the elective enables the students to acquire useful diagnostic expertise in the short time period available, and that this expertise is not rapidly forgotten after completion of the elective.Methods   In order to determine the efficacy of a 2‐week dermatology elective in promoting diagnostic skills and to ascertain the preservation of the acquired expertise, kodachrome slide‐based multiple‐choice examinations were administered to 84 sixth year medical students at the beginning (pre‐test) and completion (post‐test) of the elective. The long‐term retention of diagnostic skills was evaluated by re‐testing 4–9 months after completion of the elective (follow‐up test).Results   The mean scores of correct answers at the pre‐ and post‐test were 39.73% and 72.46%, respectively. The mean score at the follow‐up test for students with a previous dermatology elective was 80.22%, compared with a score of 46.00% for students who did not participate in the elective.Conclusions   The 2‐week dermatology elective significantly improved the diagnostic skills of the participants, and the knowledge obtained during the elective was retained for at least 4–9 months.
Shade facilitates an invasive stem succulent in a chenopod shrubland in South Australia
Authors: LENZ TANJA I. , FACELLI JOSÉ M. 
Published: October 2003

Abstract  The invasive stem succulent Orbea variegata (L) Haw. (Asclepiadaceae) tends to be more abundant underneath shrubs than in open areas in chenopod shrublands near Whyalla, South Australia. To assess the role of facilitation in the life cycle of O. variegata, we investigated the effect of chenopod shrubs on different life stages of the species by experimentally manipulating temperature, light, soil moisture and nutrient levels. Experimental results suggest that the reduction in light and temperature under shrubs, but not increased nutrient levels, are the main facilitative mechanisms for O. variegata. Temperatures above 30°C, which are more likely to occur on the soil surface of open areas than under shrubs, inhibited seed germination. Seedling survival at low watering frequency and the growth of established ramets were increased by 75–80% shade cloth. Ramets growing in full light contained a high concentration of anthocyanin pigments. One of the functions of these pigments is to absorb excess radiation, suggesting that O. variegata experiences radiation stress in full light. In the field O. variegata performed considerably better under Atriplex vesicaria Heward ex Benth. (Chenopodiaceae) or under 75–80% shade cloth than in full light. Monthly irrigation of 20 mm did not reduce this positive effect of the A. vesicaria canopy on O. variegata, suggesting that O. variegata is inhibited by high light intensities or temperatures, independent of water availability. In conclusion, whereas shrub canopies do not seem to be required for the establishment or survival of O. variegata, shrubs improve adult growth and can improve establishment. The possibility of exotic plants being facilitated by other plants has to be taken into account when assessing the probability and rate of invasion.
Rostellar apparatus of Fernandezia spinosissima (von Linstow, 1894) (Cestoda, Cyclophyllidea, Davaineidae): microanatomy and fine structure
Authors: Stoitsova Stoyanka R. , Georgiev Boyko B. , Vasileva Gergana P. , Jordanova Mimi 
Published: October 2003

AbstractThe rostellar apparatus of Fernandezia spinosissima is examined by light and transmission electron microscopy. It is described as composed of rostellum, pseudoproboscis, and two groups of glandular syncytia, one in the rostellum and the other inwards to the rostellum and the pseudoproboscis. The rostellum is a discoid cushion with muscular walls. There are numerous thin vertical muscular fibres and glandular syncytia inside it. Its tegument has slender microtriches. Peripherally, the rostellum is encircled by thin muscle fibres that protrude anteriorly between rostellar hooks and group posteriorly to form retractors. The rostellar hook guards are associated with a complicated network of muscles and nerves. The pseudoproboscis is a thick‐walled ring around the apical part of the scolex adjacent to the rostellum. Its tegument has microtriches with modified spines that are interpreted as accessory spines. The walls of the pseudoproboscis possess a loose structure of parallel muscular fibres and glandular processes. The glandular syncytia, interpreted as modified tegumental perikarya, have basophilic cytoplasm and stain positively for protein and carbohydrate. They form cellular processes, which protrude to reach to the tegument. These results provide structural details characterising one of the rostellar types recognized in the order Cyclophyllidea, i.e. the davaineid rostellar apparatus.
Mixing barley cultivars affects aphid host plant acceptance in field experiments
Authors: Ninkovic Velemir , Olsson Ulf , Pettersson Jan 
Published: October 2003

AbstractFour barley varieties with no significant difference in aphid acceptance were sown in pure stands and in pairwise combinations with varieties side by side in separate rows. Settling tests were done in situ in the field plots with apterae of Rhopalosiphum padi (L.) (Homoptera:Aphididae) and showed that aphid acceptance was changed in some combinations of cultivars. In a laboratory test, in which plants of one cultivar were exposed to air from the other cultivars, aphid acceptance was significantly reduced in three of the four cultivars when treated with air from certain other cultivars. Two of these three cultivars showed the same reduction under field conditions. This supports the hypothesis that plant/plant communication may release responses in neighbouring plants that change aphid host plant acceptance. The results also show that this mechanism is not restricted to optimal growing conditions in the laboratory, although it may be modified under field conditions depending on plant genotype.