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Biomedical subjects

C Svensson

Publications and source records attributed to C Svensson.

At least 109 records · Page 6Linked to original sources
PubMed1995

The DNA binding domains of the yeast Gal4 and human c-Jun transcription factors interact through the zinc-finger and bZIP motifs.

Different Gal4 fusion proteins, expressing unrelated transcription activator domains, were found to activate transcription from promoters containing dimerized AP1 DNA binding sites. Transactivation was dependent on the first 74 amino acids of Gal4. A direct interaction between Gal4 and c-Jun was demonstrated using a GSTGal4 fusion protein and in vitro translated human c-Jun. The interaction required the zinc finger containing DNA binding domain of Gal4 and the basic-leucine zipper region of c-Jun. These results demonstrated that the specificity of Gal4 fusion proteins in transient transfection experiments in mammalian cells is not restricted to reporters containing Gal4 binding sites, but also includes promoters containing AP1 binding sites. Furthermore, the Gal4 fusion proteins also activated transcription from a pUC18 vector fragment containing several putative AP1 binding sites. Finally, our results indicate that Gal4 activator proteins binding to Gal4 binding sites and to DNA bound AP1 factors can co-operatively activate transcription.

Base Sequence↗
PubMed1995

Mechanisms of nasal hyper-reactivity.

Hyper-reactivity to non-specific challenges has been considered a hallmark of asthma and is defined as an abnormal responsiveness of the bronchial airways to a variety of provocative agents. The mechanisms underlying hyper-reactivity in the upper and lower airways are not known. By using the nose to study the inflammatory response possible abnormalities can be investigated carefully and pathophysiology of specific airway hyper-reactivities can be better understood. Other factors than merely constriction of the bronchial smooth muscles can cause narrowing of the free lumen to airflow. Functionally different and very distinct mucosal end-organ reactivities may also be increased. If these reactivities can be well assessed, specific airway hyper-reactivity can be defined. In the present report, specific mucosal end-organ hyper-reactivities in the allergic nasal mucosa are presented. Certain widespread hypotheses, such as the role of the eosinophil and the "increased absorption permeability theory", are disputed.

Allergens↗
PubMed1995

The social network of patients with schizoaffective disorder as compared to healthy individuals.

The social network was evaluated by means of the self-rating scale 'Interview Schedule for Social Interaction' (ISSI) and semi-structured interviews in married patients with a DSM-III diagnosis of schizoaffective disorder (N = 17, partners, N = 16), married patients with diabetes (N = 10, partners, N = 10) and in married healthy individuals (N = 8, partners, N = 8). The two latter groups were comparison control groups matched for sex and age to the patients with a schizoaffective disorder. The scores on the ISSI and its subscales for the groups were compatible to those found in other Swedish studies. Patients with a schizoaffective disorder both experienced that they had less access to (AVAT) and were less satisfied with their deep emotional relations (ADAT). The same patients had a higher level of neuroticism as compared to the rest. The patients with a schizoaffective disorder had less often than the patients with diabetes been informed about their disease. Moreover, the partners to the patients with a schizoaffective disorder had not been informed about the disease and experienced that they had fewer social contacts (AVSI). A challenge for the professional network in psychiatry is to improve the information and education to families in which one member is struck by a schizoaffective disorder.

Adult↗
PubMed1995

'Tomudex' (ZD1694): results of a randomised trial in advanced colorectal cancer demonstrate efficacy and reduced mucositis and leucopenia. The 'Tomudex' Colorectal Cancer Study Group.

'Tomudex' (ZD1694), a direct and specific thymidylate synthase (TS) inhibitor entered phase III studies in November 1993. We present here the first analysis of a randomised multicentre, international phase III study. 439 patients with previously untreated advanced colorectal cancer were randomised to Tomudex 3.0 mg/m2 given once every 3 weeks or 5-fluorouracil (5-FU) 425 mg/m2 and leucovorin (LV) 20 mg/m2 for 5 days (the Mayo regimen), given every 4-5 weeks. Patients were evaluated weekly for toxicity and every 12 weeks for objective response. The two groups were well matched in terms of demographic characteristics. The mean age of the patients was 61 years and most had either liver (78%) or lung (25-29%) metastases. Ninety seven per cent of patients allocated to Tomudex and 94% of those allocated to 5-FU plus LV had measurable disease. Response was assessed using WHO/UICC criteria; all response data were source validated; 19.8% of patients who received Tomudex and 12.7% of patients who received 5-FU plus LV had complete or partial responses (P = 0.059, odds ratio 1.7, 95% confidence limits 0.98-2.81). There were no statistically significant differences in time to progression or survival between the two groups. Patients who received Tomudex spent a substantially shorter time in hospital for dosing and had significantly lower rates of grade 3 and 4 toxicities such as leucopenia and mucositis. Patients who received Tomudex had a significantly higher incidence of reversible grade 3 or 4 increase in transaminases, which appear to be of limited clinical significance. Improvement in quality of life, weight gain and performance status was seen in both groups. Tomudex has benefits in terms of higher response rates, reduced toxicity and more frequent palliative benefits when compared with 5-FU plus LV in the management of advanced colorectal cancer, and has a more convenient administration schedule.

Adult↗
PubMed1995

Effects of troponin-I extraction with vanadate and of the calcium sensitizer EMD 53998 on the rate of force generation in skinned cardiac muscle.

The rate of tension development following release of ATP from caged-ATP in the presence of calcium was studied in skinned cardiac fibres from swine. A low-force rigor state was obtained by using butanedione monoxime (BDM) during the induction of rigor. BDM was washed out and following release of ATP in the presence of Ca2+ (pCa 4.3), the muscles contracted with an apparent rate of about 2 s-1 at 22 degrees C. After treatment with 10 mM vanadate to extract troponins I and C the fibres contracted independently of calcium. The rate of contraction upon release of ATP was slower than prior to extraction and was independent of [Ca2+]. Since treatment with vanadate has been shown to extract about 90% of troponin-I the results suggest that the muscles under these conditions are partially activated by removal of an inhibition of cross-bridge interaction by troponin I. A partial recovery of force was obtained by prolonged incubation in DTT containing solutions possibly reflecting reconstitution with troponin I still present in the fibre bundle. Treatment with a solution containing whole troponin caused almost complete recovery of calcium sensitivity and rate of force development. The calcium sensitizer EMD 53998 increased rates of contraction in a dose dependent manner, suggesting that this compound increases force and calcium sensitivity by increasing the cross-bridge attachment rates.

Adenosine Triphosphate↗
PubMed1995

Allergen challenge-induced entry of alpha 2-macroglobulin and tryptase into human nasal and bronchial airways.

BACKGROUND: Microvascular-epithelial exudation of bulk plasma may characterize inflammatory airway diseases. This study compares the acute allergen challenge-induced mast cell and exudative responses in nasal and bronchial airways. The focus is on alpha 2-macroglobulin as an index of luminal entry of plasma exudates. METHODS: Separate nasal and bronchial allergen challenges were carried out outside the pollen season in eight patients with pollen-induced seasonal allergic rhinitis. The levels of different-sized plasma proteins (albumin molecular weight, 66,000 d and alpha 2-macroglobulin molecular weight, 725,000 d) and tryptase were determined in pre- and postchallenge nasal lavage and bronchoalveolar lavage (BAL) fluids. Diluent and increasing doses of allergen were sprayed into the right nasal cavity, and each challenge was followed by a nasal lavage (volume, 15 ml) with a "nasal pool" device (recovery, > 80%). Endobronchial allergen challenge (individual doses) and BAL (volume, 2 x 25 ml) were performed in a lobe bronchus through a fiberoptic bronchoscope (recovery, 30%). Saline challenge and BAL were carried out in the contralateral lung as control. RESULTS: The levels of albumin, alpha 2-macroglobulin, and tryptase increased dose-dependently in postchallenge nasal lavage fluids (p < 0.05) and correlated to nasal symptoms. In particular, albumin and alpha 2-macroglobulin correlated (r = 0.98, p < 0.001). Both alpha 2-macroglobulin and tryptase, but not albumin, were increased in BAL fluids from the allergen-challenged side (p < 0.05). CONCLUSION: Local allergen challenge causes luminal entry of tryptase and alpha 2-macroglobulin in the nose and bronchi of patients with allergy. We suggest that mast cell and plasma exudation responses may be similar in human nasal and bronchial airways and that albumin levels (in BAL fluids) may not well reflect the exudation process in bronchial airways.

Adult↗
PubMed1995

Loratadine reduces allergen-induced mucosal output of alpha 2-macroglobulin and tryptase in allergic rhinitis.

BACKGROUND: Despite the wide use of antihistamines in the treatment of allergic rhinitis, little is known about effects of these drugs on airway mucosal indices, which specifically reflect either mast cell release activity (tryptase) or microvascular-epithelial exudation of bulk plasma (alpha 2-macroglobulin). OBJECTIVE: This study, involving subjects with seasonal allergic rhinitis, examines the effects of loratadine treatment on allergen-induced nasal mucosal output of tryptase and alpha 2-macroglobulin. Effects on nasal symptoms and eosinophils are also examined. METHODS: Placebo and loratadine (20 mg) were given orally once daily for 5 days at 6-week intervals. Nasal diluent and allergen challenges were carried out on day 5. The mucosa was lavaged with saline solution after each challenge, and nasal lavage fluid levels of tryptase and alpha 2-macroglobulin were determined. Nasal symptoms were scored, and nasal peak expiratory flow rates were measured. Superficial cells (eosinophils) were obtained with a brush device before and 24 hours after the allergen challenges. RESULTS: Allergen dose-dependently increased the nasal symptoms and the lavage fluid levels of alpha 2-macroglobulin and tryptase. Allergen also reduced the nasal peak expiratory flow rates. Loratadine inhibited the exudation of alpha 2-macroglobulin and reduced tryptase levels, nasal symptoms, and obstruction, but did not affect the number of eosinophils. CONCLUSION: The inhibitory effects of loratadine on nasal lavage fluid levels of alpha 2-macroglobulin suggest that histamine, through effects on microvascular H1-receptors, mediates allergen challenge-induced exudation of bulk plasma in acute allergic rhinitis. The reduced lavage fluid levels of tryptase suggest either that loratadine directly attenuates mast cell release activity or that loratadine, through inhibition of the exudation process, simply attenuates luminal entry of tissue solutes (in this case, tryptase).

Adolescent↗
PubMed1995

Exudative hyperresponsiveness of the airway microcirculation in seasonal allergic rhinitis.

BACKGROUND: Mucosal exudation of plasma is a non-injurious, physiological response of the airway microcirculation to different inflammatory processes. The exudative response is similar in the nose and bronchi and exudation occurs in both allergic asthma and rhinitis. The exudative response is a specific end-organ function of the mucosal microcirculation that may be altered in airway diseases. OBJECTIVE: This study examines the hypothesis of altered responsiveness of the superficial airway microcirculation to vascular permeability-increasing challenges in sustained allergic inflammation. METHODS: Fourteen patients with birch-pollen induced allergic rhinitis were studied for 7 weeks during a Swedish birch-pollen season. Nasal symptoms (itching, sneezing, blockage, and discharge) were recorded and the occurrence of pollen was determined. The plasma exudation response was examined by topical histamine challenges at the end (May) and well out of (December) the season. Challenge and lavage were carried out concomitantly using a 'nasal pool'-device. The unilateral nasal cavity was filled for consecutive 10 minute periods with saline and two concentrations of histamine (80 micrograms/mL and 400 micrograms/mL). The lavage fluid levels of different-sized plasma proteins (albumin-66,000 D, fibrinogen-340,000 D, and alpha 2-macroglobulin-725,000 D) were determined. RESULTS: The pollen season was mild resulting in only minor nasal symptoms. Histamine produced exudation of all plasma proteins across the microvascular epithelial barriers with particularly strong correlation between the levels of albumin and alpha 2-macroglobulin (r = 0.98; P < 0.001). The exudative response to histamine was concentration-dependent (P < 0.05) and, furthermore, it was significantly greater late into the season compared with outside the pollen season (albumin: P < 0.05, fibrinogen; P < 0.05, alpha 2-macroglobulin: P < 0.01). CONCLUSION: We conclude that histamine produced concentration-dependent nasal airway exudation of bulk plasma in subjects with seasonal rhinitis and that this response is abnormally great during the pollen season. Whether angiogenesis or increased responsiveness of the microvascular endothelium may explain this phenomenon now remains unknown. We suggest that a microvascular exudative hyperresponsiveness may characterize allergic airway disease.

Adult↗
PubMed1995

Nasal cytokines in common cold and allergic rhinitis.

Coronavirus-induced common cold and allergen-induced rhinitis are characterized by nasal mucosal exudation of bulk blood plasma. The mucosal exudation process involves 'flooding' of the lamina propria with plasma-derived binding proteins and it is possible that subepithelial inflammatory cytokines and mediators may be moved by the exudate to the mucosal surface. In this study, we have analysed cytokine levels in nasal lavage (NAL) fluids from non-allergic subjects inoculated with coronavirus (n = 20) and from subjects with allergic (birch pollen) rhinitis subjected to additional allergen challenge (samples were obtained 35 min post challenge) in the laboratory (n = 10). Ten of the 20 inoculated subjects developed common cold and 10 remained healthy. Interferon-gamma (IFN gamma), interleukin-1 beta (IL-1 beta), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, and IL-6 were analysed in unprocessed NAL fluids using immunoassays. The subjects who developed common cold had increased NAL fluid levels of IFN gamma (P < 0.05) that correlated well with the symptoms (P < 0.001). IFN gamma did not increase in subjects with allergic rhinitis. IL-1 beta levels were similar in NAL fluids obtained from all inoculated subjects. In the subjects with allergic rhinitis NAL fluid levels of both IL-1 beta and GM-CSF were increased (P < 0.05). GM-CSF was not detected in common cold. IL-4 and IL-6 were not detectable in any of the NAL fluids. The present cytokines may not only emanate from superficial mucosal cells. By aiding plasma exudation subepithelial cytokines may potentially also be retrieved on the mucosal surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Topical nitroprusside may reduce histamine-induced plasma exudation in human nasal airways.

Mucosal exudation of nonsieved bulk plasma is a key feature of airway defense and inflammation. We have previously observed in guinea pig tracheobronchial airways that endogenous nitric oxide (NO) of the mucosa may tonically suppress the permeability of the subepithelial microcirculation, and that topical administration of the NO donor nitroprusside may reduce plasma exudation responses. The present study examines whether nitroprusside affects histamine-induced mucosal exudation of plasma in the human nasal airway. In a dose-finding tolerability experiment, using changes in nasal patency as response, placebo and nitroprusside (1.2 and 3.6 mg per nasal cavity) were applied on the mucosal surface with a nasal-spray device. Nasal peak expiratory flow (PEF) rates were measured before the application and thereafter every third minute for 15 min. Nitroprusside produced a dose-dependent decrease in nasal PEF rates compared to placebo. Placebo or nitroprusside (7.2 mg) was then given to the right nasal cavity, followed 3 min later by challenge with saline or histamine (600 micrograms). The drug and the challenge were both applied with a nasal-spray device. With a nasal pool-device, the same large part of the nasal mucosal surface was lavaged before and after the treatment/challenge. The lavage fluid levels of alpha 2-macroglobulin were measured as an index of mucosal exudation of bulk plasma. The histamine-induced lavage fluid level of alpha 2-macroglobulin was significantly higher after treatment with placebo than with nitroprusside. The present data indicate that nitroprusside may have antiexudative effects in human airways. Hence, unlike other microvascular permeability active agents, this pharmacologic principle may be active in both guinea pig and human airways.

Administration, Topical↗
PubMed1995

Antiallergic actions of high topical doses of terbutaline in human nasal airways.

It is debatable whether beta 2-receptor agonists produce antiallergic effects in human airways. This question has been addressed in the present study by examination of both mast-cell indices and the physiologic response to allergen challenge in human nasal airways. Twelve asymptomatic patients with seasonal allergic rhinitis were investigated outside the pollen season. Intranasal allergen provocation was carried out with diluent and three increasing doses of allergen. Topical terbutaline sulfate (1.0 mg) was given 5 min prior to each allergen challenge and nasal lavage was carried out 10 min after each challenge. The study design was double-blind, placebo-controlled, crossover, and randomized. The allergen challenge-induced mast-cell activation and the ensuing physiologic response of the airway tissue were investigated by measuring a mast-cell-derived mediator (tryptase) and plasma proteins (albumin and alpha 2-macroglobulin), respectively, in the lavage fluids. Allergen provocation produced dose-dependent increments of nasal symptoms and lavage fluid levels of tryptase, albumin and alpha 2-macroglobulin. Both nasal symptoms (P < 0.05) and lavage fluid levels of tryptase (P < 0.05), albumin (P < 0.05), and alpha 2-macroglobulin (P < 0.01) were reduced by pretreatment with topical terbutaline sulfate. We conclude that high doses of topical terbutaline may produce significant antiallergic effects in human airways by equally reducing both tryptase release and plasma exudation in the acute allergic reaction in human airways. Further studies are now warranted to determine whether microvascular antipermeability effects of beta 2-receptor stimulation contribute to the present observations.

Administration, Topical↗
PubMed1995

Effects of topical capsaicin in seasonal allergic rhinitis.

BACKGROUND: Mucosal exudation (luminal entry) of bulk plasma is a key feature of airway defence and inflammation. In guinea pig and rat airways this response is readily produced by neurogenic irritants, notably capsaicin. Thus "neurogenic airway inflammation" has become an established concept. The present study examines whether capsaicin also produces mucosal exudation of plasma in human nasal airways both in health and disease (seasonal allergic rhinitis). METHODS: Pain-producing concentrations of capsaicin (30-300 ng/ml) were applied to the nasal mucosal surface both before and late into the pollen season. Levels of albumin in nasal lavage fluid were measured as an index of mucosal exudation of plasma. In a separate group of patients with seasonal allergic rhinitis nasal challenge with an exudative concentration of histamine was carried out before the birch pollen season and concentrations of albumin in lavage fluid were measured. RESULTS: Pollen counts and symptom scores revealed a mild pollen season. Capsaicin produced considerable nasal pain and this response was augmented late into the season when capsaicin also produced nasal blockage. However, capsaicin failed to produce any mucosal exudation of plasma either before or late into the pollen season. The exudative effect of histamine was confirmed. CONCLUSIONS: The augmented pain response to capsaicin suggests that a sensory nerve hyperresponsiveness may characterise allergic airways disease. In contrast to the effects on animal airways, capsaicin failed to produce mucosal exudation of plasma in the human nasal airway. The animal based neurogenic inflammation concept is therefore not valid for the human nasal airway, not even in inflamed airways when a neural hyperresponsiveness has developed.

Administration, Topical↗
PubMed1995

Various methods for testing nasal responses in vivo: a critical review.

Mucosal responses in the airway can ideally be studied in the nose. It is a readily accessible organ and can be provoked repeatedly. Likewise, mucosal responses to certain provocations can be easily monitored. Different methods for the provocation and measurement of nasal responses have been used in recent years. Each technique has its own advantage and restrictions. In order to make a correct interpretation of the results achieved, however, it is important that the investigator is familiar and comfortable with the methods used. For clinical purposes, techniques for qualitative measurements may be appropriate, but for experimental research, quantitative measurements with high reproducibility are essential. The present paper critically discusses current techniques for provocation and assessment of nasal responses, which may improve both the techniques used and the understanding of nasal physiology.

Alkaloids↗
PubMed1995

Survival of oocysts of Eimeria alabamensis on pastures under different climatic conditions in Sweden.

The extent to which oocysts of the coccidian parasite Eimeria alabamensis can survive the winter and cause clinical coccidiosis in different parts of Sweden was investigated. Fecal samples were collected between May and July 1993 from calves on 59 farms where calves had grazed the same pasture for at least 5 consecutive years. The farms were situated in 9 regions of Sweden with different climatic conditions in the winter. On each farm, 5 samples of feces were collected from the floor of the calf-house before the calves were turned out in the spring, and again from the pasture on days 4 or 5, 8 or 9 and 10 or 11 after they were turned out. Overwintering of oocysts of E. alabamensis was considered to have occurred if an increase in the excretion rate of oocysts of this species could be demonstrated 8 to 11 days after calves had been turned out to pastures that had not been grazed since the previous autumn. Oocysts were shown to have overwintered on 27 farms, representing all 9 regions. Samples from 20 (34%) of the farms representing all the climatic regions contained more than 850,000 oocysts per g of feces. This was comparable with the numbers found in animals with clinical coccidiosis due to E. alabamensis. Delaying turnout until the beginning of July did not affect the infection rate of the calves. However, calves which were turned out to pastures that had been grazed by older cattle or horses, either earlier in the spring or in previous years, excreted significantly fewer oocysts than calves which were turned out to pastures that had been grazed only by calves. A questionnaire answered by 321 dairy farmers revealed that of the 298 farmers who turned their first-season grazing cattle out to traditional pastures, 179 (60%) had used the same pasture for at least 5 years. These 179 farmers had experienced a significantly higher incidence of diarrhoea in their calves during the first 2 weeks at pasture than those farmers who had used different pastures.

Animals↗
PubMed1994

An adenovirus E1A transcriptional repressor domain functions as an activator when tethered to a promoter.

The adenovirus E1A protein contains three well conserved regions, designated conserved region (CR) 1, 2 and 3, which are important for the multiple activities ascribed to E1A. The CR3 domain constitutes a prototypic transcription activator, consisting of a promoter targeting region and a transactivating region. Here we demonstrate the existence of a second transactivating region located within amino acids 28 to 90 (essentially the CR1 domain) of the E1A protein. A fusion protein, containing the Gal4 DNA binding domain linked to CR1, was as efficient as the classical CR3 transactivator in activating transcription from a reporter plasmid containing Gal4 binding sites. However, competition experiments suggest that Gal/CR1 and Gal/CR3 work through different cellular targets. The E1A-243R protein has previously been extensively characterized as a repressor of transcription. Here we show that a Gal4 fusion protein expressing the CR1 domain is indeed sufficient for repression of SV40 enhancer activity. Collectively, our results suggest that CR1 functions as an activator if tethered to a promoter and as a repressor in the absence of promoter association.

Adenovirus E1A Proteins↗