bluuebunny/crossref_metadata_2025 huggingface dataset:
A Randomised Controlled Clinical Trial on the Additional Effect of Hypnosis in a Comprehensive Treatment Programme for In-Patients with Conversion Disorder of the Motor Type
Authors: Moene Franny C. , Spinhoven Philip , Hoogduin Kees A.L. , van Dyck Richard
Published: April 2003

Background: The primary aim of this study was threefold: (1) to examine the additional effects of hypnosis aimed at symptom reduction, using symptom-oriented and expression- and insight-oriented techniques in a comprehensive clinical treatment programme for in-patients with a persistent conversion disorder of the motor type; (2) to assess whether the level of hypnotisability was predictive of treatment outcome, and (3) to explore the efficacy of the total clinical treatment programme. Methods: The study population consisted of 45 in-patients between 18 and 65 years of age meeting the DSM-III-R criteria for conversion disorder of the motor type or somatisation disorder with motor conversion symptoms. A randomised controlled clinical trial was undertaken. The primary outcome measures were the Video Rating Scale for Motor Conversion Symptoms, the D(isabilities) code items from the International Classification of Impairments, Disabilities and Handicaps and the Symptom Checklist-90. Measures of the credibility of treatment and patient expectations of treatment outcome were used as manipulation checks. Hypnotisability was measured using the Stanford Hypnotic Clinical Scale. Results: Significant treatment results for all outcome measures were found for the total sample. These effects proved to be clinically significant. The use of hypnosis had no additional effect on treatment outcome. Hypnotisability was not predictive of treatment outcome. Conclusion: A comprehensive treatment programme, either with or without hypnosis, can be worthwhile for patients with long-standing conversion symptoms.
Prevalence of Byssinosis and Respiratory Symptoms among Cotton Mill Workers
Authors: Altin R. , Ozkurt S. , Fisekçi F. , Cimrin A.H. , Zencir M. , Sevinc C.
Published: April 2003

Background: While the prevalence of byssinosis is decreasing in industrialized countries and persists at high levels in developing countries, this prevalence is remaining constant in Turkey. Objective: In order to determine the effects of past cotton dust exposure on the respiratory tract, a total of 223 persons working in a cotton mill were included in this study. Methods: A questionnaire was used to inquire about respiratory symptoms. Participants underwent several spirometric measurements, which were performed on the 1st, 3rd and 5th day of the working week. Cotton dust measurements were performed in different divisions of the factory. Results: The most common respiratory symptom was chest tightness (20.3%). The prevalence of byssinosis was 14.2% in cotton-processing workers. Among these cases, 28.6% had symptoms on the 1st day of the week, and 71.4% had symptoms on all days of the week. An acute effect was seen in 53.6% of the workers with byssinosis. Mean respirable dust levels were between 0.095 and 0.413 mg/m3. Conclusions: In spite of technological improvements, respirable dust concentrations are still above the permissible limits, and thus the risk of byssinosis remains. Workers in the cotton industry where obsolete technology is used and standardized protection measures are not applied should be followed for byssinosis.
Do Urea/Ammonium Lactate Combinations Achieve Better Skin Protection and Hydration than Either Component Alone?
Authors: Gloor M. , Fluhr J. , Lehmann L. , Gehring W. , Thieroff-Ekerdt R.
Published: April 2003

Twenty subjects with healthy skin were treated with the following formulations for two weeks: drug-free W/O vehicle, 5% ammonium lactate (CAS 52003-58-4) in W/O vehicle, 5% urea (CAS 57-13-6) in W/O vehicle, 3% ammonium lactate + 3% urea in W/O vehicle, 5% ammonium lactate + 5% urea in W/O vehicle. These formulations were applied in randomized order to 6 test areas on the forearms; one area was left untreated. Repetitive washings were additionally performed in the second treatment week. TEWL, stratum corneum water content (corneometry-determined electrical capacitance), and cutaneous blood flow (laser Doppler) were measured at baseline, day 7, and day 14. 5% urea and both ammonium lactate/urea combinations produced significant stratum corneum hydration and improved stratum corneum barrier function; there were no significant differences between these three treatments.
Variability of Enzyme Markers during Clinical Regression of Atopic Dermatitis
Authors: Tarroux R. , Assalit M.F. , Licu D. , Périé J.J. , Redoulès D.
Published: April 2003

Skin surface enzyme activities were found to be significantly different in healthy and in skin with atopic dermatitis and, following appropriate treatment, a close correlation was observed between the clinical staging of the atopic dermatitis and the levels of the assayed marker enzymes. Samples were taken, by stripping with simple adhesive tapes, from a group of subjects on cure in a spa. The corneocytes were recovered from the first layers of the stratum corneum. Aqueous extracts of the strips were tested for their activity on chromophoric substrates which allow fluorescence spectrometry to be used to assay the trypsin-like, acid-phosphatase-like and phospholipase-A2-like activities. We show that the restoration of return to activities close to those of healthy subjects is related to the general condition of the patients, who showed a clearly improved SCORAD. Recovery of the trypsin-like activity and attenuation of the phospholipase-like activity, paralleled the regression of the dermatitis as assessed by a decrease in clinically evaluated parameters of xerosis and inflammation.
Cigarette Smoke-Induced Lipid Peroxidation in Human Skin and Its Inhibition by Topically Applied Antioxidants
Authors: Pelle E. , Miranda E.P. , Fthenakis C. , Mammone T. , Marenus K. , Maes D.
Published: April 2003

Cigarette smoke, whether indirect or direct stream, is an environmental pollutant which presents an increasing health problem. In order to determine damage to human skin at the biochemical level, volar forearms were exposed to cigarette smoke for fifteen minutes and then assayed for the presence of stratum corneum lipid peroxides. A time-dependent increase was observed over a 24-hour post-exposure period. At 24 h, the average baseline level of lipid peroxides was 14.9 nmol/unit area of skin as compared to 32.0 nmol/unit area of skin for the smoke-exposed arms. In addition, when topical antioxidants were pre-applied to the skin and then exposed to cigarette smoke, an average decrease of 40.9% in lipid peroxide values was observed. These data demonstrate that peroxidation was induced in human skin by cigarette smoke and subsequently inhibited by the presence of antioxidants.
Different Skin Thinning Potential of Equipotent Medium-Strength Glucocorticoids
Authors: Korting Hans Christian , Unholzer Angela , Schäfer-Korting Monika , Tausch Irene , Gassmueller Johannes , Nietsch Karl-Heinz
Published: April 2003

In this study, we investigated the effect of prednicarbate, mometasone furoate and betamethasone 17-valerate on total skin thickness over a treatment period of 6 weeks. The study was conducted as a double-blind, placebo-controlled randomized clinical trial with a confirmatory approach. The influence of these drugs on healthy human skin under non-occlusive conditions was assessed by measuring total skin thickness and epidermal thickness using 20 and 50 MHz sonography, respectively. Epidermal surface structure was evaluated using profilometry. Visual assessment addressed signs of atrophy and formation of telangiectasia. The reduction of total skin thickness induced by prednicarbate was clearly less than that caused by betamethasone 17-valerate and mometasone furoate. Prednicarbate led to a higher degree of skin thinning than vehicle. For technical reasons, epidermal thickness could not be reliably evaluated with 50 MHz sonography. Profilometry did not demonstrate any differences between treatments. Visible signs of atrophy or telangiectasia were detected in two subjects each upon betamethasone 17-valerate and mometasone furoate, but not upon prednicarbate or its vehicle. Prednicarbate is a topical glucocorticoid with an improved benefit/risk ratio, as it causes less skin atrophy than the equipotent betamethasone 17-valerate.
Modulation of Atopy Patch Test Reactions by Topical Treatment of Human Skin with a Fatty Acid-Rich Emollient
Authors: Billmann-Eberwein C. , Rippke F. , Ruzicka T. , Krutmann J.
Published: April 2003

Measures directed at improving the skin barrier function are thought to be effective in preventing reexacerbation of atopic dermatitis, but direct proof of a prophylactic effect of emollients has been elusive. In the present study, the atopy patch test has been employed as a model for the initiation phase of atopic dermatitis in order to assess whether pretreatment of non-lesional skin with a fatty acid-rich emollient (Eucerin® Omega Creme) has a prophylactic effect in patients with atopic dermatitis. Pretreatment of test sites with Eucerin® Omega Creme either prevented or diminished the development of eczema, as compared with untreated control test sites in the same patients (n = 38). These studies indicate that the use of fatty acid-rich emollients prevents the development of atopic eczema. They also demonstrate that the atopy patch test can be used to assess the capacity of a given regimen to exert prophylactic effects in this disease.
Modulating Effects of Oatmeal Extracts in the Sodium Lauryl Sulfate Skin Irritancy Model
Authors: Vié K. , Cours-Darne S. , Vienne M.P. , Boyer F. , Fabre B. , Dupuy P.
Published: April 2003

The aim of the present study was to assess the anti-inflammatory activity of two topically applied oatmeal extracts, i.e. Avena sativa and Avena Rhealba®, using the sodium lauryl sulfate (SLS) irritation model. At baseline, test areas on the volar surface of the upper arms of 12 healthy individuals were pretreated with the two extracts and their vehicle (petrolatum ointment) under occlusion for 2 h, and one site was left untreated. Then a patch with a 1% SLS solution was applied to the test sites for 24 h. Irritation was determined at each period by measuring by chromametry and laser-Doppler. In a dose-ranging study with the Avena Rhealba extract alone, the 20 and 30% concentrations exerted a slight inhibition of the a* parameter increase and a marked reduction of the blood flow increase (p < 0.05, compared to vehicle). Then, the effects of the two extracts at the concentration of 20% were compared. All extracts displayed a statistically significant counteracting effect on both parameters (p < 0.05), but no statistically significant difference between treatment groups could be demonstrated. In conclusion, this study demonstrates the preventive effects of oatmeal extracts on skin irritation in the SLS model.
Labor in the Grand Multipara
Authors: Lyrenäs Sven
Published: April 2003

Objective: To assess delivery time and the frequency of dystocia in grand multiparous (GMP) and grand grand multiparous (GGMP) women. Method: Labor records from 272 women with parity 4–8 (GMP) and 56 women with parity 9 or higher (GGMP) were retrospectively reviewed regarding duration of labor and the occurrence of dystocia. As a comparison, data from 263 women with parity 1–3 (LMP) and 87 nulliparas (NP) was used. Results: Duration of labor, defined as time from admission of the laboring woman to delivery of the infant, lasted in median 2.0, 2.3 and 3.1 h in LMP, GMP and GGMP, respectively. There was no difference in mean cervical dilatation on admission in multiparous women. In GGMP, the presenting part was more frequently positioned above the pelvic inlet at time of admission. In multiparous women admitted during the latent phase, the active phase of labor lasted in median 3.7 h in GMP and 4.7 h in GGMP, significantly longer than 2.9 h in LMP. During the active phase of labor, GGMP experienced arrest of cervical dilatation more frequently than the LMP. In parous women, there was a positive relationship between parity and duration of the active phase of labor as well as the duration of labor. Infant’s birth weight increased by parity. Conclusion: Duration of the active phase of labor increased after the fourth child. Failure of descent of the presenting part during the first stage of labor in addition to arrest of cervical dilatation was associated with a high cesarean section rate in the GMP woman.
Tubular Cell Apoptosis and Proliferation in the Early Phase of Renal Damage in Uninephrectomized SHR
Authors: Rodríguez-López Ana M. , Flores Olga , Arévalo Miguel A. , López-Novoa José M.
Published: April 2003

In the present study, we measured tubular cell apoptosis and proliferation and Bcl-2 expression during the early phase (3 months) of the process of renal fibrosis in the experimental model of uninephrectomized spontaneously hypertensive rats (SHR). Tubulointerstitial fibrosis was evaluated by automated quantitative morphometry using selective staining of the extracellular matrix with sirius red. Apoptosis was quantified by both in situ dUTP biotin nick end-labeling method (TUNEL) and by propidium iodide staining. Proliferation rate was measured by counting cells expressing the proliferating cell nuclear antigen. Bcl-2 expression was assessed by immunohistochemistry. Tubulointerstitial fibrosis increased progressively during the 3 months of follow-up. Proliferation and apoptosis rates in tubular cells increased from the first to the second month after UNX. In the third month after UNX, the proliferating tubular cell number continued to increase, whereas the apoptotic cell number was maintained, coinciding with an increase in the expression of Bcl-2. Our observations demonstrate a different profile of tubular cell proliferation and apoptosis during the genesis of early tubulointerstitial damage in UNX-SHR.
Influence of the Alpha-1-Adrenergic Receptor Blocker Doxazosin on Exercise-Induced Hyperkalemia in Hemodialysis Patients
Authors: Nowicki Michał , Waluś Tomasz , Kokot Franciszek
Published: April 2003

Background/Aim: Hyperkalemic responses to both physical exercise and α-adrenergic stimulation are enhanced in patients with terminal renal failure. α-Adrenergic blockade was found to protect against hyperkalemia during vigorous exercise in healthy men. The aim of the study was to examine the effects of the α-adrenergic blocker doxazosin on exercise-induced hyperkalemia in hemodialysis patients. Methods: In a randomized, placebo-controlled, crossover design study, 15 anuric, chronic hemodialysis patients were included. Doxazosin or placebo was given in a random order for 4 days before exercise. At the end of each phase of the study, a 30-min treadmill exercise test with a constant workload of 2 metabolic equivalents was performed followed by a 30-min recovery period. Results: The patients achieved 64 ± 3 and 62 ± 3% of maximal heart rate during the exercise test on doxazosin and placebo, respectively. The baseline plasma concentration of potassium was similar both on active treatment and on placebo (5.1 ± 0.2 mmol/l on doxazosin and 4.9 ± 0.1 mmol/l on placebo). The serum potassium concentration increased significantly and to a similar extent during the tests. The mean rates of potassium increment during exercise were 8.4 ± 1.5 µmol/l/min on doxazosin and 6.9 ± 1.3 µmol/l/min on placebo. During the recovery period, the serum potassium concentration significantly decreased in both arms of the study. There were no significant changes in plasma sodium, calcium, and phosphate levels during the tests. Hydrogen ion concentration in blood, serum insulin and glucose, and plasma aldosterone and renin activity were similar before the exercise tests. Conclusion: α-Adrenergic blockade does not modulate the hyperkalemic response to moderate physical exercise in patients with terminal renal failure.
Effectiveness of a Therapeutic Community Treatment in Spain: A Long-Term Follow-Up Study
Authors: Fernández-Hermida José-Ramón , Secades-Villa Roberto , Fernández-Ludeña José-Javier , Marina-González Pedro-Antonio
Published: April 2003

In this paper, the effectiveness of the treatment program developed by Proyecto Hombre (‘Project Mankind’) in Asturias, Spain, is evaluated. In a long-term follow-up (range from 73 days to 8 years) with a sample of 249 subjects, the results obtained by subjects completing the treatment (194) were compared with pre-treatment results and with those of the group that dropped out (55). The measurements used were relapses in illegal drugs, alcohol, changes in family situation, educational level, employment, criminal involvement and state of health. External validation of self-report measures given in the questionnaire was carried out. Findings support the effectiveness of the treatment in all measures and the validity of self-report items. Relapse rate in ‘treatment-completed’ group was 10.3%, whilst in the non-completers group it reached 63.6% (significant difference, p < 0.001). Relapses of non-completers were more severe, occurred sooner after leaving the program (they stayed abstinent for shorter periods) and lasted longer than those of subjects completing the treatment.
Treatment of Chronic Hepatitis C in Injecting Drug Users: 5 Years’ Follow-Up
Authors: Dalgard O. , Bjøro K. , Hellum K. , Myrvang B. , Skaug K. , Gutigard B. , Bell H.
Published: April 2003

Aim of the Study: To assess the long-term hepatitis C (HCV) treatment outcome in former injecting drug users (IDUs). Materials and Methods: A long-term follow-up of 27 former IDUs who had been successfully treated for chronic hepatitis C was performed. These patients represented all IDUs who had obtained a sustained virological response in a Norwegian HCV treatment trial. The patients had been treated with interferon-α alone or in combination with ribavirin. At 5 years’ follow-up the 27 IDUs were retested for HCV RNA and risk behaviour for HCV transmission after treatment was assessed. In the control group all 18 non-IDUs who had obtained a sustained virological response in the same treatment trial were included. Results: At follow-up 13–82 months (median 64) after the end of treatment only one case of probable reinfection was seen among the 27 IUDs. No reoccurrence of HCV was observed in the control group. The IDU who was HCV RNA positive at follow-up had continued injecting drugs and reported frequent needle sharing. At follow-up HCV of genotype 1a was detected in contrast to genotype 1b before treatment indicating that this patient was reinfected with HCV. A return to injecting drug use occurred in 9 (33%) of 27 IDUs. Conclusion: The long-term outcome of HCV treatment in former IDUs was excellent. Despite frequent reinitiation of drug injection all but 1 remained HCV RNA negative.
Some Aspects of Complementarity in the Immune System
Authors: Bakács T. , Mehrishi J. , Szabados T. , Varga L. , Tusnády G.
Published: April 2003

The burden of this paper is the suggestion that the defence capacity of the immune system is rather limited. It cannot stand in readiness to deal with a practically endless diversity and abundance of microbes. In contrast to conventional thinking the current model proposes: (1) The core idea that cells of the immune system are basically and constantly interconnected with host cells (e.g., through TCR-MHC interactions) and that foreign antigens (peptides) may tend to obstruct such interactions. Peptides presented during a viral infection typically decrease complementarity between the structures that are the products of the major histocompatibility complex (MHC) genes (or other genes related to it) and T cells. The altered MHC profile exposes infected cells to a polyclonal immune attack from other T cells such that tissue destruction occurs in an allograft rejection-like fashion. This may explain why a substantial portion of T cell numbers is activated when only a small number of specific T cells is ‘obstructed’ from functioning by the presence of nonself peptides. (2) Phagocytes ‘see’ targets even in a non-immune host because complement distribution associated with polyreactive natural antibodies magnifies sensitization differences between pathogens and host cells. (3) There is only a probability that hypermutation will successfully change the genome in some B cell clones to produce high affinity antibodies that prevent the re-infection of the host by the same pathogen, but cannot conquer primary infections. (4) The history of the development of the immune responses suggests that during prolonged interaction between host and microbes in our natural habitat, carried on over many generations, the adaptive antibody population may facilitate the evolution of the natural antibody repertoire. The model predicts that microbes, which are not a part of the local environment, may invade the organism without significant resistance. The model is discussed in various interactions for survival in the context of infection and tumorigenicity.
IgG1, IgG4 and IgE Antibody Reactivity to Mutant Forms of the Major Dust Mite Allergen Lep d 2 among Atopic and Nonatopic Subjects Naturally Exposed to Lepidoglyphus destructor
Authors: Olsson Susanna , van Hage-Hamsten Marianne , Magnusson Carl G.M.
Published: April 2003

Background: Lepidoglyphus destructor is a common dust mite causing IgE-mediated sensitization. The major allergen, Lep d 2, has previously been cloned and expressed as several double Cys to Ser mutants with the purpose of producing hypoallergenic variants for immunotherapy. Our aim was to investigate the reactivity pattern of IgG1, IgG4 and IgE antibodies to wild-type (wt) rLep d 2 and four mutants among atopic and nonatopic subjects in relation to sensitization and exposure to L. destructor. Methods: Inhibition and sandwich ELISA were used to compare IgG1, IgG4 and IgE antibody reactivities to rLep d 2 variants in serum of 20 atopic and 18 nonatopic farmers naturally exposed to L. destructor. A group of 22 urban subjects served as controls. Results: Atopic farmers demonstrated correlating IgE and IgG4 levels to rLep d 2(wt) (rs = 0.70; p < 0.0001) which were significantly (p < 0.0001) higher than those of nonatopic farmers and urban controls. No IgG4 antibodies were detected in nonatopic farmers despite chronic allergen exposure. A parallel reactivity pattern of IgE and IgG4 to all rLep d 2 mutants was observed. The mutant lacking all 3 disulfide bonds, rLep d 2.6Cys, demonstrated neither any IgE nor IgG4 reactivity. In contrast, IgG1 antibodies had a different reactivity pattern and were detected among most subjects irrespective of atopy, exposure to L. destructor or disulfide impairments in rLep d 2. Moreover, IgG1 levels to rLep d 2(wt) and rLep d 2.6Cys correlated (n = 60; rs = 0.65; p < 0.0001). Conclusions: IgE/IgG4 Ab to rLep d 2 were restricted to atopic farmers and demonstrated parallel recognition patterns of conformational epitopes. In contrast, IgG1 antibodies are ubiquitously found and mainly recognize sequential structures. The observed isotypic difference and interindividual variation in antibody specificities among atopic and nonatopic subjects imply careful investigation of hypoallergenic variants destined for immunotherapy.
Genetic Immunisation with Bovine β-Lactoglobulin cDNA Induces a Preventive and Persistent Inhibition of Specific Anti-BLG IgE Response in Mice
Authors: Adel-Patient Karine , Creminon Christophe , Boquet Didier , Wal Jean-Michel , Chatel Jean-Marc
Published: April 2003

Background: Various studies have shown that DNA immunisation with gene allergen induces a non-allergic response. Methods: We applied this new type of vaccination to bovine β-lactoglobulin (BLG), a major cow’s milk allergen, using a plasmid that allows the production of a partially secreted protein. Specific antibodies and cytokines were quantified in different immunisation protocols. Results: The primary response in mice immunised with BLG-encoding plasmid (pBLG) is of the Th1 type. Restricted recognition of a native form of BLG in pBLG mice contrasted with a broader range of recognition in BLG-in-alum-immunised mice, notwithstanding the fact that alum favours the presentation of a native form of the antigen. We also demonstrated an inhibitory effect of pDNA immunisation on the Th2 response induced by a subsequent immunisation using BLG adsorbed on alum. However, this preventive effect is highly dependent on the time of pre-administration of the pBLG, with an optimal effect when pDNA immunisation occurred at least 21 days before protein administration. This preventive effect resulted concomitantly in the inhibition of BLG-specific IgE, in the induction of specific IgG2a, and in the decrease of the specific IgG1/IgG2 ratio. It is accompanied by an increase in IFNγ and IL-10 secretion. Moreover, the preventive effect was shown to be persistent even after a booster immunisation with alum-adsorbed BLG. The Th1 orientation of the response is very likely due to the presentation of the protein in the Th1 environment due to plasmid immunostimulatory sequences, as intramuscular injection of BLG itself leads to a weak Th2 response and had no preventive effect on a subsequent sensitisation. Conclusion: This study further demonstrates the potential use of DNA immunisation for prevention of IgE response, but the window of action seems to be very restricted if we are to inhibit an established Th2 response efficiently.
Intranasal Treatment with a Recombinant Hypoallergenic Derivative of the Major Birch Pollen Allergen Bet v 1 Prevents Allergic Sensitization and Airway Inflammation in Mice
Authors: Wiedermann Ursula , Herz Udo , Baier Karin , Vrtala Susanne , Neuhaus-Steinmetz Ulrich , Bohle Barbara , Dekan Gerhard , Renz Harald , Ebner Christof , Valenta Rudolf , Kraft Dietrich
Published: April 2003

Background: The major birch pollen allergen Bet v 1 represents one of the most prevalent environmental allergens responsible for allergic airway inflammation. Objective: In the present study we sought to compare the complete recombinant Bet v 1 allergen molecule with genetically produced hypoallergenic fragments of Bet v 1 regarding mucosal tolerance induction in a mouse model of allergic asthma. Methods: BALB/c mice were intranasally treated with recombinant Bet v 1 or with two recombinant Bet v 1 fragments (F I: aa 1–74; F II: aa 75–160) prior to aerosol sensitization with birch pollen and Bet v 1. Results: Intranasal application of F II, containing the major T cell epitope, led to significant reduction of IgE/IgG1 antibody responses, in vitro cytokine production (IL-5, IFN-γ, IL-10) and negative immediate cutaneous hypersensitivity reactions comparable to the pretreatment with the complete rBet v 1 allergen. Moreover, airway inflammation (eosinophilia, IL-5) was inhibited by the pretreatment with either the complete Bet v 1 or F II. However, for prevention of airway hyperresponsiveness the complete molecule was required. The mechanisms leading to immunosuppression seemed to differ in their dependence on the conformation of the molecules, since tolerance induced with the complete Bet v 1, but not with F II, was transferable with spleen cells and associated with increased TGF-β mRNA levels. Conclusion: We conclude that mucosal tolerance induction with recombinant allergens and genetically engineered hypoallergenic derivatives thereof could provide a convenient and safe intervention strategy against type I allergy.
Tonsillar B Cells Do Not Express PSGL-1, but a Significant Fraction Displays the Cutaneous Lymphocyte Antigen and Exhibits Effective E- and P-Selectin Ligand Activity
Authors: Armerding Dieter , Fuhlbrigge Robert C. , Kieffer J. David , Kupper Thomas S.
Published: April 2003

Skin-homing T cells are defined by the expression of the cutaneous lymphocyte-associated antigen (CLA) which enables the cells to selectively bind to vascular endothelial E-selectin close to sites of cutaneous inflammation, an initial step in the effective extravasation from blood into the inflamed tissue. Essentially all CLA on T cells decorates the backbone of the P-selectin glycoprotein ligand-1 (PSGL-1). In this study we show that human peripheral blood B cells (PBBC) and tonsillar B cells (TBC) do not display PSGL-1 in fluorescence-activated cell sorter analysis using different murine monoclonal antibodies and polyclonal rabbit anti-PSGL-1 antiserum. A significant population of TBC, however, expresses a HECA-452-reactive epitope. These cells represent nonactivated IgM+/IgG– mature B lymphocytes. Up to 50% of the TBC in a given preparation strongly bind to E- and up to 79% to P-selectin. The shear stress resistance in a parallel-plate flow chamber system was high. Neuraminidase treatment of TBC totally and O-sialoglycoprotein endopeptidase partially diminished HECA-452 reactivity and reduced E- but not P-selectin ligand activities. Mocarhagin had no effect in the assays. The data suggest a different ligand for P-selectin and a distinct glycoprotein carrier for the E-selectin ligand as compared to T cells or other leukocytes. Adhesion to P-selectin, however, still required sulfation of the ligand for function. Western blots of TBC cell lysates detected a >240-kD HECA-452-reactive material that was resistant to reducing conditions. Anti-PSGL-1 did not reveal immunoreactive material in these cell lysates. B cell activation did neither significantly change HECA positivity nor induce PSGL-1 expression. Cultured, activated TBC, however, maintained expression of the integrin α4β7. Human peripheral blood B cells had similar cell surface characteristics to TBC. Our observations suggest that several adhesion molecules may be involved in B cell homing which include CLA, the P-selectin ligand, and structures such as α4β7.
A Th1-Inducing Adjuvant, MPL®, Enhances Antibody Profiles in Experimental Animals Suggesting It Has the Potential to Improve the Efficacy of Allergy Vaccines
Authors: Wheeler Alan W. , Marshall Jean S. , Ulrich J. Terry
Published: April 2003

Background: Monophosphoryl lipid A (MPL®) is a detoxified derivative of the lipopolysaccharide (LPS) moiety of Salmonella minnesota R595, which has retained immunostimulatory activities. MPL® has been administered to many subjects in clinical trials as an adjuvant component of infectious disease vaccines and is currently a component of a licensed cancer vaccine, Melacine® (Corixa Inc., Schering Plough). MPL® has, in particular, been shown to promote Th1-type antigen specific responses. L-tyrosine is a depot adjuvant which is fully metabolisable and has been successfully employed in allergy vaccines for a number of years. Methods: Mice were immunised with MPL® adjuvant in conjunction with separate preparations of either ovalbumin or glutaraldehyde-modified ragweed pollen extract both coprecipitated with L-tyrosine. The specific antibody isotypes IgG1, IgG2a, IgG2b and also IgE were measured. Rats received booster injections of keyhole limpet haemocyanin (KLH) in conjunction with MPL® adjuvant following priming with KLH in alum alone. KLH-specific antibody responses were measured. Results: It was shown that a combination of L-tyrosine and MPL® were synergistic in enhancing murine antigen specific IgG antibody responses without enhancing antigen specific IgE responses. Furthermore, this adjuvant combination promoted strong IgG2 antigen specific responses indicative of a Th1 directed response. In KLH sensitised rats, treatment with MPL® was shown to prevent a secondary IgE antibody response when injected with booster injections of antigen. Conclusions: Immunisation of mice with two different antigens adsorbed to L-tyrosine induced a Th1-skewed primary response when in conjunction with MPL® adjuvant which also generally enhances a specific IgG response. Incorporation of MPL® adjuvant in the immunisation of rats prevented a secondary specific IgE response. These results suggest that the employment of this new adjuvant in clinical allergy vaccination formulations may result in an improved efficacy which could be utilised in various ways to improve compliance.
Roles of Superoxide Dismutase in Rat Mast Cell Granules
Authors: Fukuishi Nobuyuki , Takahashi Hideaki , Harada Naoko , Kanoh Reiko , Matsui Nobuaki , Akagi Masaaki
Published: April 2003

Background: It has been suggested that in the granules of rat mast cells there is some kind of superoxide dismutase (SOD), but details of this SOD in mast cells remain unclear. In the present study, we studied the mode of existence of SOD in mast cells and its releasing mechanism from the granules. In addition, we discussed the physiological role of SOD in allergic events. Methods: Purified rat mast cells were disrupted with a sonic disrupter and granules (sample I) were separated from supernatant (sample II) by centrifugation. The granules were treated with 1 mM Ca2+, and the supernatant (sample III) was separated from the pellet (sample IV). Sample III was applied to a heparin column and the eluate was used as sample V. SOD activity was measured in these samples. Results: SOD existed in mast cell granules as a heparin-binding and an inactive form. However, when granules were released and exposed to high Ca2+ concentration, SOD was discharged from heparin and shifted to the active form. The expression of macrophage inflammatory protein-1 alpha mRNA was enhanced when hydrogen peroxide (H2O2) or sample III with the xanthine-xanthine oxidase system were added to the culture media. Conclusions: These findings suggest that in stimulated rat mast cells, the released SOD may transform the generated superoxide anion into H2O2, and the generated H2O2 may enhance the expression of chemokine mRNA in the mast cells.
Critical Role for Caspases 3 and 8 in Neutrophil But Not Eosinophil Apoptosis
Authors: Daigle Isabelle , Simon Hans-Uwe
Published: April 2003

Background: Apoptosis is a necessary process to control cell numbers in multicellular organisms. In many chronic inflammatory diseases, reduced cell death of different types of granulocytes is one important mechanism for cell accumulation. Here, we studied the role of caspases in neutrophil and eosinophil apoptosis in the presence or absence of granulocyte-macrophage stimulating factor and anti-CD95 monoclonal antibodies, respectively. Methods: Granulocytes were isolated from human blood using standard protocols. Immunoblot and functional studies with cell-permeable specific peptide inhibitors were performed to analyze caspase involvement. Fas receptor and Fas ligand expression was analyzed by RT-PCR, flow cytometry, and immunoblotting. Cell death was analyzed by ethidium bromide exclusion test. Results: Caspases 3 and 8 are critically involved in the regulation of neutrophil apoptosis in vitro. In contrast, these two caspases did not appear to play a major role in the regulation of eosinophil apoptosis. However, the broad-range caspase inhibitor VAD prevented eosinophil death, indicating that caspases are also involved within the apoptotic machinery of eosinophils. Functional inhibitor studies suggested that caspase 9 is crucial for both caspase 3 and 8 activation, at least in neutrophils. In contrast, spontaneous apoptosis of neutrophils or eosinophils is unlikely to be the consequence of Fas ligand/Fas receptor molecular interactions. Conclusion: The data of this study indicate differences in the usage of caspases between neutrophils and eosinophils.
Increased Levels of IgA Antibodies against Desmin in Children with Coeliac Disease
Authors: Teesalu K. , Uibo O. , Kalkkinen N. , Janmey P. , Uibo R.
Published: April 2003

Background: In addition to IgA anti-endomysial antibodies, IgA anti-smooth muscle antibodies have been observed in a number of patients with coeliac disease (CoD), but only limited data exist on the frequency and antigen specificity of IgA against cytoskeletal proteins in CoD. Methods: We evaluated the sera of 42 untreated CoD patients, follow-up sera of 26 CoD patients after treatment, and 116 control sera for IgA reactivity to cytoskeletal proteins from the human umbilical cord (HUC) by immunoblotting, and compared the results with anti-tissue transglutaminase IgA (anti-tTG IgA) ELISA and immunofluorescence results. Results: Serum IgA from CoD patients most frequently recognized a 57-kD antigen in HUC cytoskeletal extract, identified as desmin using mass spectrometry and internal peptide sequencing. Increased IgA reactivity to the human desmin band was detected in 22 children with untreated CoD (52.4%), in 4 treated CoD patients (15.4%), and in 12 control subjects (10.3%) (p < 0.01); similar results were obtained with anti-chicken desmin IgA ELISA. Anti-tTG IgA levels (increased in 71.4% of untreated CoD patients) correlated significantly with anti-desmin IgA levels in untreated CoD, and both autoantibody reactivities decreased in response to a gluten-free diet. Pre-adsorption experiments and affinity purification of anti-desmin IgA antibodies further confirmed that desmin is an IgA autoantigen in CoD and is recognized by antibodies which are not cross-reactive with tTG. Conclusions: Anti-desmin IgA antibodies are frequently occurring if not the predominant cytoskeletal antibodies in children with untreated CoD and could be related to the disease process in the small intestine.
Evaluation of a Dipstick Test (Allergodip®-Latex) for in vitro Diagnosis of Natural Rubber Latex Allergy
Authors: Kütting Birgitta , Weber Bernhard , Brehler Randolf
Published: April 2003

Background: IgE-mediated hypersensitivity to latex has been recognized as an increasing health problem with far-reaching consequences for patients, regarding both their occupational situation and safety in medical care. Therefore, a correct diagnosis of natural rubber latex (NRL) allergy is essential. The purpose of the study was to evaluate sensitivity and specificity of several established diagnostic methods for NRL allergy (in vitro assays and skin prick test) in relation to a new semiquantitative dipstick test (Allergodip®-Latex, Allergopharma) as a screening test for NRL allergy. Methods: Data obtained with quantitative assays including Pharmacia CAP System® (FEIA), DPC-AlaSTAT® and Magic Lite® were compared with the dipstick test results in latex-sensitized (n = 151) and nonsensitized persons (n = 232). In addition these in vitro findings were related to clinical symptoms after exposure to latex and skin prick test results with a panel of different latex allergen extracts. Results: When comparing sensitivity and specificity of all in vitro assays relative to skin prick test results the Pharmacia CAP System® (FEIA) had the highest sensitivity in the range of 90%. Sensitivity of the other in vitro assays was in the range of 73.7–74.9%, specificity varied from 85.3 to 89.8%. A diagnostic standard was defined in terms of at least three corresponding test results out of all diagnostic methods (in vitro assays and skin prick test). The sensitivity and specificity of each diagnostic test were determined relative to this diagnostic standard. Hereby the Allergodip test results showed a sensitivity of 91% and a specificity of 93%. Conclusion: The dipstick test results are in line with the data of the other in vitro assays. In contrast to other in vitro assays the dipstick test requires no further laboratory equipment and is easy to perform.
cDNA Cloning and Expression of Blo t 11, the Blomia tropicalis Allergen Homologous to Paramyosin
Authors: Ramos John Donnie A. , Cheong Nge , Lee Bee Wah , Chua Kaw Yan
Published: April 2003

Blomia tropicalis is an important mite species in many parts of the world and the most predominant mite species in tropical countries. The prevalence of sensitization to this species has probably been underestimated because commercial extracts are largely unavailable. Identification and characterization of B. tropicalis allergens is an important step toward understanding the role of this species in allergic sensitization and could provide appropriate reagents for diagnostic and therapeutic procedures. This paper describes the isolation, sequence analysis, expression and allergenicity of a cDNA gene coding for a B. tropicalis allergen with homology to paramyosin, a high-molecular-weight allergen previously identified in Dermatophagoides farinae. The full-length Blo t 11 cDNA gene was isolated by cDNA library screening, 5′-rapid amplification of cDNA ends and long-distance PCR. Sequence analysis was performed with a combination of CLUSTAL W, CGC and BLAST program packages. The cDNA gene was expressed as a GST fusion protein in Escherichia coli and purified by affinity chromatography using the glutathione Sepharose column. Allergenicity of the rBlo t 11 was tested by human IgE dot blot immunoassay. Blo t 11 is a 3,111-bp cDNA gene with a 2,625-bp open reading frame coding for an 875-amino acid protein, exhibiting significant homology with different invertebrate paramyosins. The human IgE dot blot immunoassay showed that the rBlo t 11 reacted positively to 52% (33/63) of sera from asthmatic patients. Blo t 11 is the homolog of Der f 11 exhibiting potentially important allergenic activity.
Maternal Antigen Stimulation Downregulates via Mother’s Milk the Specific Immune Responses in Young Mice
Authors: Bednar-Tantscher Eva , Mudde Geert C. , Rot Antal
Published: April 2003

Background: Different aspects of the vertical transfer of predisposition to allergy from mother to child have been investigated. An issue which is still largely open is the influence of breast-feeding by allergic mothers on the development of the allergic phenotype of the infant. In the current study we employed a murine ovalbumin (OVA) immunization model to investigate possible milk-borne influences of the mother’s specific immune status on the primary immune response of the breast-fed pup. Methods: Naïve and OVA-immunized female mice were mated simultaneously. Immediately after birth litters were exchanged between the immunized and the untreated mothers which allowed the evaluation of maternal influence exerted via milk only. At the age of 3 weeks the pups were injected with a single dose of OVA intraperitoneally and sacrificed 2 weeks later. Serum was obtained for the determination of total and OVA-specific IgE and IgG2a. In addition, lymphocyte proliferation was measured following OVA stimulation of the pups’ splenocytes and lymph node cells. During the lactation period milk was collected from the mothers for evaluation of its total and OVA-specific immunoglobulin levels. Results: Breast-feeding of naïve pups by OVA-immunized mothers results in the suppression of the pups’ specific IgE response as well as the downregulation of the OVA-induced proliferative response of the pups’ lymph node cells and splenocytes. Additionally, splenocytes of naïve pups nursed by immune mothers show a decrease in IL-4 production compared to naïve pups nursed by naïve mothers, whereas the IFN-γ production is not altered. Conclusion: We demonstrated the suppression of the pups’ primary humoral and cellular response towards OVA by breast-feeding by mothers exposed to OVA shortly before pregnancy. It appears that such a transfer of the suppressive activity from mother to pups via milk directs the pups’ immune response towards a Th1 and away from a Th2 type, thus avoiding the ‘allergic’ phenotype. Our study suggests that breast-feeding by mothers immune to an antigen may suppress the development of an allergic response to this antigen.
The Value of Pre-Emptive Analgesia in the Treatment of Postoperative Pain after Laparoscopic Cholecystectomy
Authors: Uzunköy A. , Coskun A. , Akinci O.F.
Published: April 2003

Background and Aim: Postoperative pain is an important surgical problem. Recent studies in pain pathophysiology have led to the hypothesis that with pre-operative administration of analgesics (pre-emptive analgesia) it may be possible to prevent or reduce postoperative pain. This study was planned to investigate the efficacy of pre-emptive analgesia on postoperative pain after laparoscopic cholecystectomy. Methods: 45 patients undergoing laparoscopic cholecystectomy were randomized into three groups. Bupivacaine was injected into the area of skin incision before trocar entry and after trocar removal in group 1 and 2, respectively; however, this procedure was not applied to the control group. The pain score of the patients was evaluated by the visual analogue scale (VAS) at 1, 4, 12and 24 h after surgery. The daily analgesic requirement was evaluated in terms of diclophenac sodium (Diclomec, Abdi Ibrahim, 75 mg) intake/day. Analgesics were given to the patients whose VAS was 5 or higher. Results: While there was no significant difference in VAS scores between group 1 and 2, the mean pain scores of these two groups were found to be significantly lower than of the control group although the analgesic requirement of the patients in each group was not statistically significant. Conclusion: Pre-emptive analgesia is as effective as postsurgical local anaesthesia in reducing postoperative pain.
Does the Administration Route of Leucovorin Have Any Influence on the Impairment of Colonic Healing Caused by Intraperitoneal 5-Fluorouracil Treatment?
Authors: Hacıyanlı M. , Fuzun M. , Unek T. , Tokgoz Z.
Published: April 2003

Intraperitoneal chemotherapy with 5-fluorouracil (5-FU) is a new, promising alternative in adjuvant treatment of advanced colorectal cancer. Leucovorin (LV), a biomodulator of 5-FU, potentiates the antineoplastic effect of 5-FU. The aim of this study was to determine whether the administration routes of LV had any influence on the impairment of colonic healing caused by intraperitoneal 5-FU treatment. 48 male Wistar rats were subjected to left colonic resection and anastomosis, and randomized to 1 of 4 groups: control group (receiving intraperitoneal NaCl, intravenous NaCl); ipFU group (receiving intraperitoneal 5-FU, intravenous NaCl); ipFU+ivLV group (receiving intraperitoneal 5-FU, intravenous LV), and ipFU+LV group (receiving intraperitoneal 5-FU+LV, intravenous NaCl). Treatment was started after surgery and continued for 5 days with daily injections. The animals were sacrificed on the 7th day postoperatively. Anastomotic complications were more common in the ipFU, ipFU+ivLV, and ipFU+LV groups (p < 0.05) compared to the control group. The anastomotic breaking strength was significantly reduced in the ipFU, ipFU+ivLV, ipFU+LV groups (p < 0.05) than in the control group, but it did not differ between the ipFU, ipFU+ivLV, and ipFU+LV groups. The hydroxyproline content of the anastomotic segment was also significantly reduced in the ipFU, ipFU+ivLV and ipFU+LV groups (p < 0.05) compared to the control group. However, there was no difference between the anastomotic hydroxyproline content of the ipFU, ipFU+ivLV, and ipFU+LV groups. In this experiment, colonic healing was impaired after intraperitoneal 5-FU administration as judged by the higher rates of anastomotic complications, reductions in anastomotic breaking strength and hydroxyproline content; but LV administration either intravenously or intraperitoneally did not cause further deterioration in colonic healing.
Effects of Zinc Deficiency and Corticosterone Elevation on Bone Marrow in Rats
Authors: Mori T. , Tani T. , Hanasawa K. , Kodama M.
Published: April 2003

Objective: The effects of zinc deficiency and serum corticosterone elevation, in a zinc-deficient state, on rat bone marrow were studied. Materials and Methods: Male Sprague-Dawley rats were divided into the following four groups: zinc-adequate (ZA), restricted ZA (RZA), zinc-deficient (ZD) and ZD with the injection of Mifepristone (ZD+Mife). Platelet and reticulocyte counts, levels of serum zinc and corticosterone, bone marrow cellularity and morphological alterations of marrow were examined in all rats. Results: Decreased marrow cellularity, decreased numbers of peripheral platelets and reticulocytes, and increased adipocytes in the marrow were observed in ZD rats. The injection of Mifepristone improved marrow cellularity, and increased the number of platelets, while decreasing adipocytes in the marrow in ZD rats. Conclusion: Both zinc deficiency itself and the associated serum corticosterone elevation induced bone marrow suppression in rats.