bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose‐ and time‐dependency of the dilator effects of the endothelin antagonist, BQ‐123, in the human forearm
Authors: Berrazueta José R. , Bhagat Kiran , Vallance Patrick , MacAllister Raymond J. 
Published: October 2003

Aims Endothelin‐1 is a potent endogenous vasoconstrictor that acts on the endothelin A (ETA ) receptor. The dose‐response and time‐course of the dilator effect of the ETA receptor antagonist, BQ‐123, was investigated in the forearm of healthy volunteers. Methods Forearm blood flow was measured using mercury‐in rubber strain gauge venous occlusion plethysmography. Results Following intra‐arterial infusion of BQ‐123 (50 nmol min−1 ) for 5 min, forearm blood flow increased by approximately 60% over the next 60 minutes; lower doses were without significant effect. The degree of dilatation was similar to that observed in previous studies using 20‐fold larger doses. Conclusions This study confirms that basal endothelin‐1 has a role in the physiological regulation of vascular tone. It is possible that at low doses, BQ‐123 might be a more sensitive pharmacological tool for the detection of abnormal endothelin‐1 mediated constriction.
Remission maintenance therapy with histamine and interleukin‐2 in acute myelogenous leukaemia
Authors: Brune Mats , Hellstrand Kristoffer 
Published: October 2003

Peripheral blasts recovered from patients with acute myelogenous leukaemia (AML) were efficiently lysed by interleukin‐2 (IL‐2)‐activated heterologous natural killer (NK) cells in vitro. The IL‐2‐induced killing of AML blasts was inhibited by monocytes, recovered from peripheral blood by centrifugal elutriation. Histamine, of concentrations within the micromolar range, abrogated the monocyte‐induced inhibition of NK‐cells; thereby, histamine and IL‐2 synergistically induced NK‐cell‐mediated killing of AML blasts. The effect of histamine was apparently mediated by H2‐type histamine receptors (H2R), since the H2R antagonist ranitidine completely blocked the response.Based on these in vitro findings, seven patients with AML in first (n=2), second (n=3) or third (n=2) complete remission (CR) were given home therapy with interleukin‐2 (IL‐2; 0.9×106 IU×2 s.c.) and histamine (0.4–0.7 mg×2 s.c.) in cycles of 21 d, separated by 6‐week intervals. The patients also received treatment with low‐dose cytarabine and thioguanine between cycles of histamine/IL‐2. Toxicity was moderate and included local reactions to IL‐2 at the site of injection and short‐lasting flush, hypotension, and headache to histamine. The addition of histamine to treatment with IL‐2 significantly enhanced the accumulation of CD25+ T cells in peripheral blood as compared to treatment with IL‐2 alone (P<0.003). Five patients remain in complete remission at 9, 18, 21, 24 and 26 months; the two patients in CR3 relapsed after 8 and 33 months, respectively. In the five patients with earlier relapse, the duration of remission after treatment with histamine/IL‐2 has in each case exceeded that of previous remissions. We conclude that (i) histamine and IL‐2 synergize to kill human AML blasts in vitro, and (ii) histamine/IL‐2 is a safe and feasible approach to immunotherapy of AML which merits further investigation.
Marrow transplantation for Fanconi anaemia: conditioning with reduced doses of cyclophosphamide without radiation
Authors: Flowers Mary E. D. , Zanis Jose , Pasquini Ricardo , Deeg H. Joachim , Ribeiro Raul , Longton Gary , Medeiros Carlos R. , Doney Kristine , Sanders Jean , Bryant Eileen , Hansen John , Sullivan Keith M. , Appelbaum Frederick , Thomas E. Donnall , Storb Rainer 
Published: October 2003

Nine patients with Fanconi anaemia (FA) were conditioned for HLA‐identical sibling bone marrow transplant (BMT) with reduced dose of cyclophosphamide (Cy) without radiation or antithymocyte globulin (ATG). The total dose of Cy was 140 mg/kg (n=2) or 120 mg/kg (n=7). The median patient age was 8 years (range 4–19). Graft‐versus‐host disease (GVHD) prophylaxis was with methotrexate and cyclosporine (n=8) or cyclosporine alone (n=1). All patients had sustained engraftment and two developed grade ≥II acute GVHD. Cy toxicity included grade ≥2 mucositis seen in all evaluable patients and haemorrhagic cystitis in two patients. The Kaplan‐Meier survival estimate is 89% with a median follow‐up of 285 d (range 56–528).For the purpose of comparison, this report also reviews and updates long‐term follow‐up data on 32 previously reported FA patients conditioned with 140–200 mg Cy/kg without radiation.The lowest dose of Cy (without radiation or ATG) after which HLA‐identical sibling marrow transplant can be successfully performed in FA patients has yet to be determined, but it appears that uniform and sustained engraftment can be achieved with a Cy dose of as low as 120 mg/kg.
Progesterone increases airway eosinophilia and hyper‐responsiveness in a murine model of allergic asthma
Authors: Hellings P. W. , Vandekerckhove P. , Claeys R. , Billen J. , Kasran A. , Ceuppens J. L. 
Published: October 2003

SummaryBackground
Sex hormones might affect the severity and evolution of bronchial asthma. From existing literature, there exists, however, no convincing evidence for either exacerbation or improvement of allergic symptoms by progesterone.Objective
This study was aimed to explore the effect of exogenously administered progesterone in a mouse model of allergic asthma.Methods
BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injections with OVA followed by chronic inhalation of nebulized OVA or physiologic saline (Sal). Medroxyprogesterone acetate or placebo was instilled daily into the oesophagus before and during the inhalatory OVA challenge phase.Results
Progesterone worsened allergic airway inflammation in OVA‐challenged mice, as evidenced by enhanced bronchial responsiveness to inhaled metacholine and increased bronchial eosinophilia. Elevated airway eosinophilia corresponded with higher bronchial and systemic IL‐5 levels in the progesterone group. The ratio of IL‐4/IFN‐γ levels in bronchoalveolar lavage fluid and numbers of eosinophil colony‐forming units in the bone marrow were also elevated in the latter group. Progesterone, however, did not influence allergen‐specific IgE production, nor did it affect bronchial responses in Sal‐challenged mice.Conclusion
Our data show that exogenously administered progesterone aggravates the phenotype of eosinophilic airway inflammation in mice by enhancing systemic IL‐5 production. Progesterone also increases bronchial hyper‐reactivity.
Primary sensitization to sweet bell pepper pollen in greenhouse workers with occupational allergy
Authors: Vermeulen A. M. , Groenewoud G. C. M. , De Jong N. W. , De Groot H. , Gerth van Wijk R. , Van Toorenenbergen A. W. 
Published: October 2003

SummaryBackground
In a previous investigation, a high prevalence of allergy to sweet bell pepper pollen was found among exposed horticulture workers. Allergy to plant‐derived food is often the consequence of primary sensitization to common pollen allergens.Objective
We therefore investigated the cross‐reactivity between sweet bell pepper pollen and pollen from grass, birch or mugwort.Method
We selected 10 sera from greenhouse workers who had, besides specific IgE against sweet bell pepper pollen, also IgE to grass, birch or mugwort pollen. Cross‐reactivity was tested by the inhibition of IgE binding to solid‐phase coupled sweet bell pepper pollen extract. The 10 sera were also analysed for IgE binding to sweet bell pepper pollen by immunoblotting.Results
With these sera, no or small inhibition of IgE binding to sweet bell pepper pollen extract was observed with grass, birch and mugwort pollen. With immunoblotting, major IgE‐binding structures were seen at 14, 29 and 69 kDa in sweet bell pepper pollen extract.Conclusion
The results of our study demonstrate that sweet bell pepper pollen contains allergens that have no or limited cross‐reactivity with common pollen allergens. With sera from the 10 patients tested, sensitization to sweet bell pepper pollen was not the consequence of primary sensitization to common pollen allergens.
Regulation of procollagen I (α1) by interleukin‐4 in human bronchial fibroblasts: a possible role in airway remodelling in asthma
Authors: Bergeron C. , Pagé N. , Joubert P. , Barbeau B. , Hamid Q. , Chakir J. 
Published: October 2003

SummaryBackgroundIn bronchial mucosa, T cells are in close association with fibroblasts. This cell contact raises the possibility of cross‐talk between the two cell types through cytokines, such as interleukin‐4 (IL‐4).ObjectiveWe postulated that IL‐4 may modulate collagen synthesis and degradation in the fibroblasts of asthmatics.MethodsBronchial fibroblasts from asthmatics (BAF) and normal controls (BNF) were stimulated with IL‐4. Procollagen I gene expression and protein production were measured by real‐time PCR, RT‐PCR, and radioimmunoassay. The effect of IL‐4 on the regulation of procollagen I (α1) promoter was studied through transient cell transfections. The implication of Sp1 and AP‐1 in regulating IL‐4‐induced procollagen I (α1) production was determined. The effect of IL‐4 on metalloproteinase‐2 (MMP‐2) and tissue inhibitor of metalloproteinase‐2 (TIMP‐2) production and gene expression was evaluated.ResultsFollowing IL‐4 stimulation, there was a significant increase in the expression of mRNA of procollagen I (α1) by human bronchial fibroblasts of asthmatics and controls. IL‐4 has a dose–response effect on mRNA, with a maximal effect at 5 ng/mL, as determined by real‐time PCR. The maximal increase in procollagen I (α1) was observed at 6 h after IL‐4 stimulation in both BNF and BAF. BAFs have a greater increase in the procollagen I (α1)/β2microglobulin ratio after 6 h of IL‐4 stimulation (4.1×10−2±0.03 to 20.8×10−2±0.1) compared with BNF (2.9×10−2±0.006 to 9.2×10−2±0.08) (P=0.001). In transient transfection experiments, IL‐4 increased promoter activity by threefold in BAF and BNF. Sp1 was up‐regulated after IL‐4 stimulation and AP‐1 was down‐regulated as shown by electrophoretic mobility shift assay. IL‐4 decreased MMP‐2 protein and mRNA levels, and did not alter TIMP‐2 production.ConclusionsIL‐4 positively regulates procollagen I (α1) transcription by direct promoter activation and increases the TIMP‐2/MMP‐2 ratio, thereby supporting the profibrotic effect of this cytokine. Thus, this study emphasizes that IL‐4 may be considered as a link between inflammation and collagen deposition observed in asthmatic airways.
Sputum eosinophilia in cough‐variant asthma as a predictor of the subsequent development of classic asthma
Authors: Kim C. K. , Kim J. T. , Kang H. , Yoo Y. , Koh Y. Y. 
Published: October 2003

SummaryBackground
A significant proportion of patients diagnosed with cough‐variant asthma eventually manifest classic asthma signs, such as wheezing and dyspnoea. The aim of this study was to investigate whether the percentage of eosinophils and/or concentration of eosinophilic cationic protein (ECP) in sputum induced from patients with cough‐variant asthma can predict the development of classic asthma.Methods
Sixty‐two children with cough‐variant asthma were prospectively studied for 4 years. At the initiation of the study, sputum was induced with hypertonic saline, and the sputum samples were analysed for total and differential cell counts, and for ECP. Each subject was checked clinically at least every 3 months, and details of classic asthma signs experienced during the intervening periods were taken.Results
Twenty‐four (47.1%) of the 51 subjects available for follow‐up developed signs of classic asthma, while 27 did not. The only significant difference in the sputum parameters between these two groups was a higher percentage of sputum eosinophils in subjects who developed classic asthma. A significant association was found between sputum eosinophil percentage and classic asthma development, but not between the concentration of sputum ECP and classic asthma development.Conclusion
Sputum eosinophilia in cough‐variant asthma may be a correlate of the later development of classic asthma. This suggests that sputum differential cell counts may be useful in the clinical management of patients with cough‐variant asthma, as they may enable the prediction of the subsequent classic asthma development.
Effectiveness of nursing interventions in people with personality disorders
Authors: Woods Phil , Richards David 
Published: October 2003

Background. Nurses usually provide care for people with personality disorders on a day‐to‐day basis. Consequently, it is important to establish how effective nursing interventions are for those with personality disorders, both in terms of general management and more specific therapeutic approaches. These are also issues of current political and professional debate. The crucial question, however, for planners, providers and commissioners of services is, What research evidence is there about effectiveness? There is also a need to determine what further research is necessary to evaluate programmes for managing or modifying behaviours.Aim. The aim of this paper is to report on a systematic review of the literature on the effectiveness of nursing interventions in people with personality disorders, whether delivered by nurses alone or in combination with other health care professionals.Method. The review was conducted according to the United Kingdom National Health Service Centre for Reviews and Dissemination guidelines. Literature was identified from electronic database searching, footnote chasing, hand searching of journals and contact with authors of studies. Narrative synthesis was undertaken in relation to study design, participants, and type of intervention.Findings. Eighteen separate studies were included in the review: four randomized controlled trials, four non‐randomized controlled trials, seven before‐and‐after studies and three case studies.Conclusions. There is a weak evidence‐base for what constitutes effective nursing intervention with people with personality disorders. There is stronger evidence from mixed disciplines intervention studies than from nursing only intervention studies. Studies of interventions based on psychological approaches show greater improvements in outcomes than nursing management studies.
Are the measures used to calculate BMI accurate and valid for the use in older people?
Authors: Kirk S.F.L. , Hawke T. , Sandford S. , Wilks Z. , Lawrenson S. 
Published: October 2003

Body mass index (BMI) is widely accepted as the ‘gold standard’ for determining whether a patient is underweight or overweight. However, its use and accuracy is dependent on obtaining accurate measures of height and weight. Physiological changes, equipment variability and observer error leads to height being a measure fraught with inaccuracy. This has led to the development of other measures to calculate height, including demi‐span and knee height. But how much more accurate are these alternatives? The aim of this pilot study was to compare three anthropometric methods for measuring height in older people standing height, demi‐span and knee height.Seventeen subjects from a residential home in Leeds were chosen for the study, based on their ability to comply with the study protocol. Each subject was measured using a portable stadiometer for standing height, which was then adjusted for knee height, and a tape measure for demi‐span. All measurements were taken by the same researcher (TH). Measurements for demi‐span and knee height were converted using standard reference equations (for demi‐span: Bassey, 1986; for knee height: Chumlea, 1985). Data were analysed using SPSS. The Bland–Altman (1986) method for assessing agreement between two methods of measurements was carried out on the data.Data were obtained on 15 of the 17 subjects, as two subjects were unable to be weighed. Statistical analysis revealed that the lines of agreement between the three methods varied by up to 10 cm from the average or expected figure. In other words, there was up to 10 cm difference in height when calculated by the three different methods. In over half of the 17 subjects, an accurate measurement of standing height was difficult to obtain, because of difficulties encountered by the subjects in standing fully upright through frailty or spinal deformity. Problems were also encountered with demi‐span and knee height measurements, as some subjects had poor movement in their arms and were unable to stretch their arms out fully and 11 of 17 subjects were unable to get themselves into the correct position for measuring knee height.Although only conducted on a small sample of older people, the findings of this study highlight the difficulties in obtaining accurate height measurements for calculating BMI. While the literature suggests that demi‐span and knee height are reliable alternative methods for estimating stature, this was not the case in this study and may therefore also be a problem in clinical practice. Coupled with problems in the use of BMI in older people, the utility of performing such measures is debatable.
From tissue to cellular ultrastructure: closing the gap between micro‐ and nanostructural imaging
Authors: Biel S. S. , Kawaschinski K. , Wittern K.‐P. , Hintze U. , Wepf R. 
Published: October 2003

SummaryStructural investigation of tissue biopsies requires the coupling of optimal structural sample preservation with detailed information collected at the light and electron microscopic level. Unfortunately, although cryo‐immobilization by high‐pressure freezing provides the best structural preservation, it is used routinely only for electron microscopic (EM) investigations, whereas for light microscopy chemical fixation protocols have been established. These chemically invasive fixation protocols have the drawback of introducing unpredictable fixation artefacts. Therefore, comparative histopathological (i.e. light microscopic) and ultrastructural (i.e. EM) results are usually obtained from parallel samples that have not been prepared identically and never by examining exactly the same features in exactly the same, optimally preserved sample. Finally, finding an area of interest for EM investigation within a complex tissue is like searching for a needle in a haystack. To overcome these handicaps, we modified the well‐established freeze‐substitution technique (FS) to allow us to investigate resin‐embedded cryo‐immobilized tissue by confocal laser scanning microscopy (CLSM) prior to EM examination. Thus (1) selected cells throughout the whole tissue block can be depicted by CLSM and subsequently (2) selectively prepared by targeted sectioning for follow‐up investigation of the identical structure by transmission electron microscopy. This is facilitated by the addition of specific fluorescent dyes during the first FS exchange step. Selective binding properties of various dyes to different cellular structures allow a direct histological description of the tissue at the light microscope level. After embedding and preparation of a blockface, the specimen can first be examined by CLSM. For areas of interest, the depth in the resin block is determined followed by removal of the tissue lying above. Then, the cell layer can be cut into a series of ultrathin sections and examined by EM for determination of the subcellular and nanostructural organization.
High‐pressure freezing in the study of animal pathogens
Authors: Monaghan P. , Cook H. , Hawes P. , Simpson J. , Tomley F. 
Published: October 2003

SummaryHigh‐pressure freezing is applicable to both morphological and immunocytochemical studies. We are investigating the morphogenesis of foot‐and‐mouth disease virus and African swine fever virus by the use of high‐pressure freezing of infected cells. Foot‐and‐mouth disease virus particles are not detected in sections of conventionally immersion‐fixed infected cells, but when the cells are prepared by high‐pressure freezing, newly formed virions are readily seen throughout the cell. We report two methods for high‐pressure freezing of virally infected cells: first, two sapphire discs frozen ‘face to face’ with a narrow spacer to prevent cell damage and, second, a fibrous filter substrate that can be easily cut into discs to fit into the freezing planchettes. Cells readily adhere to the fibres in vitro, and the complete disc can be rapidly transferred to the planchettes for freezing. Immunolabelling studies of the microneme proteins of the parasite Eimeria tenella indicate that high‐pressure freezing followed by freeze‐substitution in acetone with uranyl acetate allows high‐sensitivity immunolabelling for these proteins.
Cryoimmobilization and three‐dimensional visualization of C. elegans ultrastructure
Authors: Müller‐Reichert T. , Hohenberg H. , O'Toole E. T. , Mcdonald K. 
Published: October 2003

Summary Caenorhabditis elegans is one of the most important genetic systems used in current biological research. Increasingly, these genetics‐based research projects are including ultrastructural analyses in their attempts to understand the molecular basis for cell function. Here, we present and review state‐of‐the‐art methods for both ultrastructural analysis and immunogold localization in C. elegans. For the initial cryofixation, high‐pressure freezing is the method of choice, and in this article we describe two different strategies to prepare these nematode worms for rapid freezing. The first method takes advantage of transparent, porous cellulose capillary tubes to contain the worms, and the second packs the worms in E. coli and/or yeast paste prior to freezing. The latter method facilitates embedding of C. elegans in a thin layer of resin so individual worms can be staged, selected and precisely orientated for serial sectioning followed by immunolabelling or electron tomography.
Examination of Bcl‐2, Bcl‐X and bax protein expression in psoriasis
Authors: Koçak Mukadder , Bozdoǧan Önder , Erkek Emel , Atasoy Pínar , Birol Ahu 
Published: October 2003

AbstractBackground  Psoriasis is an inflammatory skin disease characterized by epidermal hyperplasia and greatly accelerated epidermal turnover. The blockage of normal apoptotic process in the epidermis is one of the factors implicated in the pathogenesis of psoriasis.Objective  The purpose of the present study was to elucidate whether bcl‐family proteins are significantly involved in the hypothetical antiapoptotic cascade in lesional psoriatic epidermis.Methods  Twenty‐six lesional biopsy samples of 26 patients with psoriasis and five control specimens from normal skin were studied by immunohistochemical method for the differential expression of pro‐apoptotic bax and antiapoptotic bcl‐2 and bcl‐x proteins.Results  Compared with the normal epidermis, bcl‐2 expression was significantly reduced, whereas bax and bcl‐x were significantly overexpressed in the psoriatic epidermis. The localization of bcl‐2/bax/bcl‐x proteins in the psoriatic epidermis did not show a significant deviation from that in the normal epidermis.Conclusion  These findings indicate a discordant expression of bcl‐2 and bax/bcl‐x in psoriatic epidermis. Increased bcl‐x expression might contribute to the antiapoptotic response in psoriatic keratinocytes. The presence of strong bax expression with a concomitant decrease in bcl‐2 expression suggests either a functional defect in bax protein or an inherent/acquired resistance to bax‐mediated apoptosis in psoriatic keratinocytes.