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Biomedical subjects

C Svensson

Publications and source records attributed to C Svensson.

At least 37 records · Page 2Linked to original sources
PubMed2001

A field survey on the status of internal parasites in calves on organic dairy farms in southwestern Sweden.

Infections with internal parasites are one of the most important causes of reduced productivity in first-grazing season cattle (FGSC). In conventional herds, nematode infections can be controlled by prophylactic anthelmintic treatments, but this is prohibited in organic production. The purpose of this investigation was to monitor the status of internal parasitism on 15 organic cattle enterprises in southwestern Sweden during the 1997 and 1998 grazing seasons, and to estimate the benefits of some management practices in parasite control. On each farm, the numbers of Eimeria alabamensis oocysts per gram of (opg) faeces were counted in seven fresh dung pats collected from the paddock 8-10 days after the turnout of FGSC. Faecal samples from 5 to 15 FGSC were also analysed for nematode eggs per gram (epg) faeces at four occasions during each grazing season. In addition, the FGSC and one group of second-grazing season cattle (SGSC) were weighed at turnout and housing and at the same time blood samples were collected, and analysed for serum pepsinogen concentration and antibodies against the lungworm, Dictyocaulus viviparus. On seven farms, 1-6 samples with more than 100000 opg were found, indicating considerable pasture contamination by E. alabamensis. However, clinical signs of coccidiosis were not observed. The highest outputs of nematode eggs were observed 45-55 days after turnout. More than 500 epg were only observed in 12 (2.2%) of the calves in 1997 and in three (0.6%) animals in 1998. Only 1% of the serum samples had pepsinogen values exceeding 3.6 U tyrosine, indicative of subclinical Ostertagia ostertagi infection. Lungworm infection was detected in five and nine herds in 1997 and 1998, respectively. The number of seropositive animals on these farms ranged between one (10%) and seven (70%). Clinical signs of dictyocaulosis were observed on two farms. The results indicate that dictyocaulosis is a problem in organic dairy herds in Sweden. On the other hand, the study shows that good management such as usage of parasite safe pastures and supplementary feeding may help control gastrointestinal parasites.

Animals↗
PubMed2001

Small molecule peptidomimetics containing a novel phosphotyrosine bioisostere inhibit protein tyrosine phosphatase 1B and augment insulin action.

Protein tyrosine phosphatase 1B (PTP1B) attenuates insulin signaling by catalyzing dephosphorylation of insulin receptors (IR) and is an attractive target of potential new drugs for treating the insulin resistance that is central to type II diabetes. Several analogues of cholecystokinin(26)(-)(33) (CCK-8) were found to be surprisingly potent inhibitors of PTP1B, and a common N-terminal tripeptide, N-acetyl-Asp-Tyr(SO(3)H)-Nle-, was shown to be necessary and sufficient for inhibition. This tripeptide was modified to reduce size and peptide character, and to replace the metabolically unstable sulfotyrosyl group. This led to the discovery of a novel phosphotyrosine bioisostere, 2-carboxymethoxybenzoic acid, and to analogues that were >100-fold more potent than the CCK-8 analogues and >10-fold selective for PTP1B over two other PTP enzymes (LAR and SHP-2), a dual specificity phosphatase (cdc25b), and a serine/threonine phosphatase (calcineurin). These inhibitors disrupted the binding of PTP1B to activated IR in vitro and prevented the loss of tyrosine kinase (IRTK) activity that accompanied PTP1B-catalyzed dephosphorylation of IR. Introduction of these poorly cell permeant inhibitors into insulin-treated cells by microinjection (oocytes) or by esterification to more lipophilic proinhibitors (3T3-L1 adipocytes and L6 myocytes) resulted in increased potency, but not efficacy, of insulin. In some instances, PTP1B inhibitors were insulin-mimetic, suggesting that in unstimulated cells PTP1B may suppress basal IRTK activity. X-ray crystallography of PTP1B-inhibitor complexes revealed that binding of an inhibitor incorporating phenyl-O-malonic acid as a phosphotyrosine bioisostere occurred with the mobile WPD loop in the open conformation, while a closely related inhibitor with a 2-carboxymethoxybenzoic acid bioisostere bound with the WPD loop closed, perhaps accounting for its superior potency. These CCK-derived peptidomimetic inhibitors of PTP1B represent a novel template for further development of potent, selective inhibitors, and their cell activity further justifies the selection of PTP1B as a therapeutic target.

3T3 Cells↗
PubMed2001

Mucosal output of eotaxin in allergic rhinitis and its attenuation by topical glucocorticosteroid treatment.

BACKGROUND: Eotaxin is a chemokine that attracts and activates eosinophils. The present study examines the occurrence of eotaxin in nasal mucosal surface liquids in patients with seasonal allergic rhinitis without allergen exposure and during repeat allergen challenge with and without topical glucocorticosteroid treatment. The number of subepithelial eosinophils and mucosal outputs of bulk plasma (alpha2-macroglobulin) and eosinophil cationic protein (ECP) are also examined. METHODS: Twelve patients underwent daily allergen challenges for 6 days. Separately, 14 patients, who were receiving budesonide and placebo in a parallel group design, also underwent allergen challenge for 6 days. Nasal biopsies were obtained before and 24 h after the allergen challenge series, and lavages were carried out before and 15 min after selected allergen challenges. RESULTS: At baseline nasal lavage fluid levels of eotaxin correlated to levels of alpha2-macroglobulin and ECP. After the first allergen challenge there was a correlation between nasal lavage fluid levels of eotaxin and ECP. Repeat allergen exposure increased the mucosal output of eotaxin (P <0.05) and ECP (P <0.01) as well as eosinophil numbers (P <0.01), but no correlation was found between increased eosinophil numbers and eotaxin. Budesonide reduced eotaxin levels during repeat allergen challenge (P <0.05). CONCLUSIONS: Repeat allergen exposure in allergic rhinitis is associated with increased mucosal output of eotaxin. Topical budesonide attenuates this effect, suggesting the possibility that inhibitory effects on mucosal eotaxin may contribute to anti-eosinophilic actions of topical glucocorticosteroids.

Administration, Intranasal↗
PubMed2001

Evaluation of surgery for acromegaly: role of intraoperative growth hormone measurement?

OBJECTIVE: Intraoperative growth hormone (GH ) measurement has earlier been tried to improve surgery for acromegaly. We calculated GH half-life after adenomectomy and evaluated the possible role of this variable in predicting the final outcome of pituitary surgery in 28 consecutive patients with acromegaly. The sensitivity, specificity and predictive values were determined in relation to the results from GH suppression during an oral glucose load and IGF-1 3 months postoperatively. The GH half-life data were also compared to the corresponding results obtained from GH measurements between 60 min and 180 min after adenomectomy, and early, within 1 week, postoperatively. RESULTS: GH half-life < or =31 min was recorded in 8/13 cured patients but also in 2/15 unsuccessful cases. A mean GH concentration < or =4.4 mU/L between 60 min and 120 min after adenomectomy was found in 11/13 cured subjects but also in 3/15 not cured patients. A mean GH < or =4.0 mU/L between 90 min and 180 min was found in 11/13 cured and in 4/15 not cured patients. A mean early postoperative GH concentration < or =2.6 mU/L was noted in all 13 cured patients, but also in 2/13 unsuccessful cases. The specificity of early postoperative GH < or = 2.6 mU/L was 100% compared to 62% for a GH half-life < or =31 min (p<0.05) and 85% for the GH mean values between 60 min and 120 min and 90 min and 180 min, respectively. The sensitivity for persistent disease of values above the four cut-off limits used was between 73% and 87%. The positive predictive value for a mean early postoperative GH value >2.6 mU/L was 100%, and 72% for a GH half-life >31 min (n.s.). CONCLUSION: Although intraoperative GH half-life might be useful in some cases, it was not a reliable tool for predicting outcome of pituitary surgery in acromegaly. In cases with a 51% decrease of a basal GH concentration >5.5 mU/L, mean GH values < or =4 to < or =4.4 mU/L late intraoperatively were more informative but not as good as those obtained from the mean of a series of GH values drawn on one occasion within 1 week postoperatively, offering a 100% specificity for cure if < or =2.6 mU/L. Intraoperative GH half-life measurements should therefore be used with caution. The predictive values of the cut-off limits used in this study should be further evaluated before general application.

Acromegaly↗
PubMed2001

Immune-specific up-regulation of adseverin gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

To identify genes that are regulated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and possibly involved in TCDD-induced immunotoxicity, we used the differential display technique to screen for differentially expressed genes in the mouse thymus. Here we show that TCDD increased the expression of adseverin, a Ca(2+)-dependent, actin-severing protein. The induction of adseverin is dose- and time-dependent in parallel with the induction of CYP1A1, which is currently the most frequently used marker for TCDD exposure. A comparison between mouse strains with different TCDD responsiveness indicated that the induction of adseverin is dependent on the aryl hydrocarbon receptor, a transcription factor known to mediate most of TCDD's biological effects. Examination of additional organs revealed that the up-regulation of the adseverin gene expression is immune-specific. Using an anti-adseverin antibody, we confirmed the induction of adseverin by TCDD at the protein level and it was confined to the thymic cortex, which harbors immature thymocytes that are known target cells of TCDD. Considering adseverin's role in actin cytoskeletal reorganization, our observations reveal new mechanistic aspects of how TCDD might exert some of its immunotoxic effects.

Actins↗
PubMed2001

An automated flinch detecting system for use in the formalin nociceptive bioassay.

The biphasic display of paw-flinch behavior in the rat after injection of formalin into the dorsum of the hind paw is used for the screening of anti-hyperalgesic agents. Described and characterized here is a less labor-intensive system for counting flinch activity by detecting movement of a small metal band placed on the formalin-injected paw. A signal is generated as the band breaks the electromagnetic field of a loop antenna located under the rat and processed through an algorithm that determines flinch activity using 1) amplitude, 2) zero-voltage crossing, and 3) signal duration. Flinches are summed and stored over a selected collection interval throughout the assay for later analysis. Studies have validated the measures with respect to 1) system stability over time; 2) system-to-"practiced observer" correlation on flinch detection, r2 = 0.94; 3) system variables including time of day, sex, age, and body weight; and 4) 50% effective dose values similar to those previously reported for intrathecal morphine and the NMDA antagonist MK-801.

Analgesics↗
PubMed2001

Prevalence of nasal symptoms and their relation to self-reported asthma and chronic bronchitis/emphysema.

Little information is available on associations between rhinitis and chronic bronchitis/emphysema (CBE). Self-reported upper airway symptoms, asthma, and CBE were examined in 12,079 adults living in southern Sweden. The response rate was 70% (n=8,469), of whom 33% reported significant nasal symptoms: a blocked nose was reported by 21%; sneezing by 18%; nasal discharge by 17%; and thick yellow nasal discharge by 5.7%. Nasal symptoms and combined nasal and self-reported bronchial disease were generally more common among smokers than nonsmokers. There was little overlap between asthma and CBE, but 46% of those with asthma and 40% of those with CBE had significant nasal symptoms. Best predicting factors (odds ratios >3) for asthma and CBE were nasal symptoms due to exposure to animals and damp/cold air, respectively. One-third of an adult, southern Swedish population, had significant allergic and/or nonallergic nasal symptoms. Nasal symptoms were frequently found to coexist with both asthma and chronic bronchitis/emphysema, suggesting that pan-airway engagement is common in both diseases. Differing associations between types of nasal symptoms and allergic and irritant triggers of nasal symptoms, with regard to asthma and chronic bronchitis/emphysema, emphasize the different natures of these bronchial diseases.

Adult↗
PubMed2001

Housing, feeding and management of calves and replacement heifers in Swedish dairy herds.

A questionnaire was sent to 1500 randomly selected dairy herds in Sweden, asking for general information about the herds, including routines from birth to first calving and also routines at breeding, calving and during the grazing period. Fifty-eight percent of the questionnaires were returned. The preweaned calves were kept in individual calf pens in 68% and in group housing systems in 28% of the herds. Pens with slatted floors were the main housing system for replacement heifers from weaning to breeding, and tie stalls from breeding to first calving. Whole milk was used in 44% and milk replacements in 42% of the herds. The calves received, as a median, 2.5 litres of milk per meal and 2 meals per day. The median age at weaning was 8 weeks. Age was the single most common criteria used for deciding both weaning and breeding time. The median age when the heifers were first turned out to pasture was 6 months. Prophylactic anthelmintic treatment was used by 65% of the herds. The most common diet for replacement heifers before calving was a combination of grain, hay and silage.

Age Factors↗
PubMed2001

Cheetah teams.

Your crucial new product is on the fast track, when suddenly a problem develops that threatens to derail it. Time to bring in the cheetah team.

Commerce↗
PubMed2000

Abnormalities on chest radiographs following radiation therapy for breast cancer.

The aim of this study was to study pulmonary radiological abnormalities with chest radiography following different radiotherapy (RT) techniques for breast cancer with respect to regions and density, and their association with pulmonary complications and reduction in vital capacity (VC). Chest radiographs were performed 5 months following local or loco-regional RT in 167 breast cancer patients. The radiological abnormalities were analysed with a classification system originally proposed by Arriagada and evaluated according to increasing density (0-3) and affected lung regions (apical-lateral, basal-lateral, central-parahilar). The highest-density grades in each region were added together to form scores ranging from 0 to 9. The patients were monitored for RT-induced pulmonary complications. The VC was measured prior to and 5 months following RT. An independent evaluation of 51 patients was performed by a second radiologist to control the reproducibility of the classification system. Increasing scores were associated with loco-regional RT and pulmonary complications (P < 0.001). The mean reduction of VC for patients scoring 0-3 (-30 ml) vs 4-9 (-161 ml) was not statistically significant (P = 0.10). Scores of 4-9 were more frequently observed in older patients (P < 0.001). The independent evaluations by two radiologists revealed good agreement (P < 0.001) and no systematic inter-observer variation. Radiological abnormalities on chest radiographs, scored according to Arriagada, can be used as an objective end point for RT-induced pulmonary side effects in breast cancer.

Breast Neoplasms↗
PubMed2000

Dose-dependent effects of budesonide aqueous nasal spray on symptoms in a daily nasal allergen challenge model.

BACKGROUND: It has been difficult to demonstrate dose-dependent clinical effects of anti-allergic glucocorticosteroid drugs in allergic rhinitis. OBJECTIVE: To determine dose-dependent effects on rhinitis symptoms of clinical doses of the glucocorticosteroid budesonide in a standardized daily allergen challenge model. METHODS: Twenty-five patients with seasonal allergic rhinitis were examined outside the pollen season. The highest 256 microg once daily and lowest 64 microg once daily clinically recommended doses of budesonide aqueous nasal spray and placebo were given in a double-blind, placebo-controlled, randomized, and crossover design with 4 weeks' washout between treatments. After 1 week's treatment, the patients received individually titrated nasal allergen challenges once every morning for 8 days while treatment continued. Nasal symptoms were scored in diary cards. Nasal symptoms from the 6th to the 8th challenge days were used in the analysis. RESULTS: The provocation model produced clinically relevant, and around the clock well tolerable rhinitis symptoms, suggesting that after several days of repeated allergen challenges, a season-like, transient allergic disease condition had been established. Both 64 microg and 256 microg of budesonide aqueous nasal spray reduced nasal symptoms. Budesonide 64 microg reduced total nasal symptoms scores from 5.19 +/- 0.5 to 4.23 +/- 0.53 (P < .05), and budesonide 256 microg reduced total nasal symptoms scores to 3.41 +/- 0.51 (P < .001). A significant difference in nasal symptoms after challenge between budesonide aqueous nasal spray 64 microg and 256 microg (P = .03), indicated a dose-dependent effect. CONCLUSIONS: A dose-dependent, symptom-reducing effect of once-daily treatment with topical aqueous nasal sprays of budesonide for two weeks was demonstrated, suggesting that this model is relevant for assessments of dose-dependent effects of anti-inflammatory drugs.

Administration, Intranasal↗
PubMed2000

Glucose kinase of Streptomyces coelicolor A3(2): large-scale purification and biochemical analysis.

Glucose kinase of Streptomyces coelicolor A3(2) is essential for glucose utilisation and is required for carbon catabolite repression (CCR) exerted through glucose and other carbon sources. The protein belongs to the ROK-family, which comprises bacterial sugar kinases and regulators. To better understand glucose kinase function, we have monitored the cellular activity and demonstrated that the choice of carbon sources did not significantly change the synthesis and activity of the enzyme. The DNA sequence of the Streptomyces lividans glucose kinase gene glkA was determined. The predicted gene product of 317 amino acids was found to be identical to S. coelicolor glucose kinase, suggesting a similar role for this protein in both organisms. A procedure was developed to produce pure histidine-tagged glucose kinase with a yield of approximately 10 mg/l culture. The protein was stable for several weeks and was used to raise polyclonal antibodies. Purified glucose kinase was used to explore protein-protein interaction by surface plasmon resonance. The experiments revealed the existence of a binding activity present in S. coelicolor cell extracts. This indicated that glucose kinase may interact with (an)other factor(s), most likely of protein nature. A possible cross-talk with proteins of the phosphotransferase system, which are involved in carbon catabolite repression in other bacteria, was investigated.

Cloning, Molecular↗
PubMed2000

Excretion of Eimeria alabamensis oocysts in grazing calves and young stock.

The aims of the present study were to investigate the excretion of Eimeria alabamensis oocysts by young cattle during their first grazing season and during the first 16 days of their second grazing period. In trial 1, nine first-season grazing heifers were studied and found to have become infected with E. alabamensis shortly after turnout. The next grazing period they were turned out on to a permanent pasture together with two first-season grazing calves. Faecal samples were collected before turnout and then daily from day 3 to day 16. The second-season grazing heifers excreted insignificant numbers of E. alabamensis oocysts, whereas one of the two first-season grazing calves excreted up to 703,000 oocysts/g of faeces (OPG), indicating that the pasture was contaminated. In trial 2, faecal samples were collected from 12 calves before their first turnout in May, daily from day 2 to day 20 after turnout and then once a week until the end of September. The calves grazed pastures used in previous years by first-season grazing calves. Nine of the calves developed clinical E. alabamensis coccidiosis 4-7 days after turnout and excreted more than 950,000 OPG on days 9-10. By day 17 the oocyst excretion had decreased below 900 OPG and remained low throughout the rest of the grazing season. The results of the two studies indicate that reinfections with E. alabamensis are of little clinical importance in calves grazing contaminated pastures, and that young stock infected with E. alabamensis during their first grazing season may be used to cleanse contaminated pastures without risk of developing clinical coccidiosis.

Animals↗
PubMed2000

Modulated structure of Ag2SnO3 studied by high-resolution electron microscopy

The modulated structure of Ag2SnO3, disilver tin trioxide, was investigated by high-resolution electron microscopy and electron diffraction along four different directions. Electron diffraction showed an incommensurate one-dimensional modulated structure with a modulation wavevector of 1/6.4a*. High-resolution images showed a large number of superstructure domains with the size range 10-100 nm and orientations related by hexagonal rotation. The modulation was determined to be displacements along the c axis of the Ag atoms both in octahedral and linear coordination. An approximate structure model with a commensurate sixfold superstructure, with an orthorhombic cell (P2(1)2(1)2(1), a = 2.922, b = 1.267, c = 0.562 nm), is proposed. Calculated images and electron diffraction patterns, based on this model, agree well with experimental observations.

Journal Article↗
PubMed2000

Immediate effect of topical budesonide on allergen challenge-induced nasal mucosal fluid levels of granulocyte-macrophage colony-stimulating factor and interleukin-5.

The nasal antiinflammatory effects produced by maintenance treatment with topical steroids include reduced production of cytokines. The present study explored nasal mucosal effects induced during the first 9 h after a single dose of topical budesonide. Nine subjects with allergic rhinitis due to birch or timothy pollen were given budesonide (256 microg; Rhinocort Aqua) or placebo in a double-blind, randomized, crossover (4 wk washout) manner. Nasal allergen challenges were performed 30 min after the steroid/placebo pretreatment. Before and 30 min, 1, 3, 5, 7, and 9 h after challenge, filter paper strips were placed on the nasal septum and inferior turbinates for 10 min to sample undiluted mucosal fluids. Strips were then extracted in 1 ml buffer for cytokine analysis (ELISA). Allergen challenge produced acute nasal symptoms that peaked at 30 min and then tapered off. Conversely, both GM-CSF and IL-5 were increased only at 3, 5, 7 and 9 h (p < 0.05 compared with baseline). Budesonide did not affect the nasal symptoms but inhibited (p < 0. 05; compared with placebo treatment) the allergen challenge-induced mucosal output of GM-CSF and IL-5. These data demonstrate that GM-CSF and IL-5 are induced in a nonsymptomatic, late phase response to nasal allergen challenge, and that this cytokine response is prevented by single dose budesonide pretreatment.

Administration, Intranasal↗
PubMed1999

Crystal structure of a mammalian purple acid phosphatase.

Tartrate-resistant acid phosphatase (TRAP) is a mammalian di-iron- containing enzyme that belongs to the family of purple acid phosphatases (PAP). It is highly expressed in a limited number of tissues, predominantly in bone-resorbing osteoclasts and in macrophages of spleen. We have determined the crystal structure of rat TRAP in complex with a phosphate ion to 2.7 A resolution. The fold resembles that of the catalytic domain of kidney bean purple acid phosphatase (KBPAP), although the sequence similarity is limited to the active site residues. A surface loop near the active site is absent due to proteolysis, leaving the active-site easily accessible from the surrounding solvent. This, we believe, gives a structural explanation for the observed proteolytic activation of TRAP. The current structure was determined at a relatively high pH and without any external reducing agents. It is likely that it represents an oxidized and therefore catalytically inactive form of the enzyme.

Acid Phosphatase↗
PubMed1999

Abnormalities by pulmonary regions studied with computer tomography following local or local-regional radiotherapy for breast cancer.

PURPOSE: To study pulmonary radiological abnormalities with computer tomography (CT) following different radiotherapy (RT) techniques for breast cancer with respect to regions and density, and their correlation to pulmonary complications and reduction in vital capacity (VC). METHODS AND MATERIALS: CT scans of the lungs were performed prior to and 4 months following RT in 105 breast cancer patients treated with local or local-regional RT. The radiological abnormalities were analyzed with a CT-adapted modification of a classification system originally proposed by Arriagada, and scored according to increasing density (0-3) and affected lung regions (apical-lateral, central-parahilar, basal-lateral). The highest density grade in each region were added together to form scores ranging from 0-9. The patients were monitored for RT-induced pulmonary complications. VC was measured prior to and 5 months following RT. RESULTS: Increasing CT scores were correlated with both local-regional RT and pulmonary complications (p < 0.001). The mean reduction of VC for patients scoring 4-9 (-202 ml) was larger than for patients scoring 0-3 (-2 ml) (p = 0.035). The effect of confounding factors on the radiological scoring was tested in the local-regional RT group. Scores of 4-9 were less frequently seen in the patients who had received adjuvant chemotherapy prior to RT. The importance of the respective lung regions on the outcome of pulmonary complications was tested. Only radiological abnormalities in the central-parahilar and apical-lateral regions were significantly correlated to pulmonary complications. DISCUSSION: Radiological abnormalities detected on CT images and scored with a modification of Arriagada's classification system can be used as an objective endpoint for pulmonary side effects in breast cancer. The described model should, however, be expanded with information about the volume of lung affected in each region before definite conclusions can be drawn concerning each region's relative importance for the development of pulmonary complications. The negative association between sequential chemotherapy and radiological abnormalities should be confirmed in future studies.

Breast Neoplasms↗