[Intranasal steroids and perforation of the septum. An overlooked complication?].
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Administration, Intranasal↗
Biomedical subjects
M Andersson
Publications and source records attributed to M Andersson.
NK-lysin, a disulfide-containing effector peptide of T-lymphocytes, is reduced and inactivated by human thioredoxin reductase. Implication for a protective mechanism against NK-lysin cytotoxicity.
The cytotoxic and antibacterial polypeptide NK-lysin has a molecular mass of approximately 9 kDa and contains three disulfide bonds. The activity was highly dependent on intact disulfides, because the bactericidal effect on Escherichia coli and the cytolytic effect on human 3B6 lymphocytes was inhibited when NK-lysin was treated with dithiothreitol prior to incubation with the cells. NK-lysin was a direct substrate for human or calf thymus thioredoxin reductase and preincubation of the peptide with mammalian thioredoxin reductase, and NADPH abolished its antibacterial and cytolytic activities. The addition of human thioredoxin further enhanced the inhibitory effect of thioredoxin reductase and NADPH. In contrast, e. coli thioredoxin reductase showed no direct disulfide reductase activity with NK-lysin in agreement with previous data showing large differences in structure and substrate specificity between the mammalian and E. coli enzymes. NK-lysin is the first identified macromolecular disulfide substrate for human thioredoxin reductase apart from human thioredoxin. When 3B6 cells were incubated with NADPH, thioredoxin, and thioredoxin reductase prior to addition of NK-lysin, cytotoxicity was markedly reduced. These data suggest that thioredoxin reductase inactivates NK-lysin and provides a mechanism by which the cytotoxic activity of NK-lysin is regulated.
Cells, Cultured↗
Elastase inhibitory capacity of purified canine alpha-1-antitrypsin.
In a previous study, isoelectrofocusing of serum from liver-diseased and healthy dogs revealed three different types of the acute phase protein, alpha-1-antitrypsin: Pi (protease inhibitor) F, Pi I and Pi S. Moreover, accumulated alpha-1-antitrypsin was found immunohistochemically in liver sections from dogs with chronic liver disease, predominantly in association with Pi I in serum. The present study was made to further the relationship between alpha-1-antitrypsin and the pathogenesis of chronic liver disease in dogs. Aliquots of samples of purified canine Pi F, Pi I and Pi S were examined for elastase inhibitory capacity, the main function of alpha-l-antitrypsin, and for polymerization tendency, a possible cause of accumulation of alpha-1-antitrypsin in the liver. These parameters were studied after incubation of the proteins at different temperatures (4, 37 and 42 degrees C) and pH values (6.8, 7.8 and 8.5) and for different periods (< or = 24 h and 5 days). In contrast to findings with Pi Z, the human alpha-1-antitrypsin variant associated with liver disease, polymers of canine Pi F, Pi I or Pi S could not be detected under any of the conditions tested. However, Pi I was sensitive to pH, as was demonstrated by reduced elastase inhibitory capacity after incubation at pH 6.8 for < or = 24 h or 5 days, or at pH 8.5 for 5 days. However, after incubation at pH 7.8 for < or = 24 h or 5 days at 4, 37 or 42 degrees C, Pi I was completely stable. Pi F retained its elastase inhibitory capacity, even after prolonged incubation, at all pH values and temperatures tested. Due to low yield, Pi S was tested only after incubation for < or = 24 h at pH 6.8 and at 4 degrees C; under these conditions its elastase inhibitory capacity was equal to that of Pi F. Taken together, these findings indicate molecular and functional differences between Pi I and Pi F and further support a role for alpha-1-antitrypsin in the pathogenesis of canine liver disease.
Animals↗
Calpains in the human lens: relations to membranes and possible role in cataract formation.
Calpains are Ca-activated neutral proteases present in all cells together with an endogenous inhibitor, calpastatin. Proposed substrates are; cytoskeletal proteins like microtubules and actin, protein kinases such as PKC and membrane-bound enzymes like Ca-ATPase and the Ca-channel. In lenses from different species calpains have been detected in decreasing amounts from the epithelium to the cortex to the nucleus. Several substrates for calpain in the lens have been demonstrated: crystallins, vimentin, actin, beaded filaments and MP26 among others. Both studies on animal models and capsulorhexis indicate that calpains are mainly involved in cortical cataract.
Calcium↗
Immediate and late adverse reactions in coronary angiography. A comparison between iodixanol and ioxaglate.
PURPOSE AND METHODS: In 120 patients in a double-blind, randomized, pa rallel study, iodixanol (Visipaque), a nonionic dimer isotonic with blood, was compared with ioxaglate (Hexabrix), an ionic low-osmolar dimer, in coronary angiography regarding early and late adverse reactions. Haemodynamic and electrophysiologic parameters were also analyzed. RESULTS: Visipaque resulted in significantly fewer early adverse contrast medium-related reactions (p<0.05). Visipaque also demonstrated significantly fewer effects on electrophysiologic parameters. Both contrast media reduced systolic and diastolic blood pressures at the 1st injection in the left coronary artery. Late adverse reactions were unusual with both contrast media and occurred only as urticaria with a frequency of 1.7%, which is lower than reported in i.v. studies. One serious adverse reaction, a myocardial infarction in a male patient with severe cardiovascular disease, occurred in the Visipaque group. This event was considered to be procedure- and disease-related rather than related to the type of contrast medium used. CONCLUSION: We found Visipaque safe for coronary angiography, causing fewer early adverse reactions than Hexabrix and also fewer effects on electrophysiologic parameters. Late adverse reactions seemed to be unusual with intra-arterial administration of contrast media.
Contrast Media↗
Structural studies of the extracellular polysaccharide from Butyrivibrio fibrisolvens strain 49.
The structure of Butyrivibrio fibrisolvens strain 49 capsular polysaccharide has been investigated mainly by sugar and methylation analysis, partial chemical degradations, NMR spectroscopy, and mass spectrometry. The results suggest that the polysaccharide is composed of pentasaccharide repeating units having the following structure. [formula: see text] The polysaccharide contains O-acetyl groups, one of which is substituted to O-3 of the 4-substituted alpha-D-Galp residue, while others occur in non-stoichiometric amounts at other locations.
Bacterial Capsules↗
Lung carcinoma and malignant mesothelioma in patients exposed to Thorotrast: incidence, histology and p53 status.
In a previous registry-based survey of 999 patients injected with alpha-emitting 232ThO2 (Thorotrast), we identified elevated risks for lung carcinoma and malignant mesothelioma. Since injected Thorotrast is retained lifelong mostly in liver, spleen and lymph nodes, the mesothelial surfaces of these organs are constantly irradiated. Thorotrast-administered patients also perpetually exhale 220Rn, a 232Th-daughter. Study of Thorotrast-exposed patients may, therefore, provide data with regard to carcinogenicity of radon exposure, a current public health concern, as well as the pathogenesis of malignant mesothelioma. The incidence and histologic types of lung carcinoma and malignant mesothelioma within the cohort were examined by review of available histopathologic material and medical records. Further, mutations of the p53 gene were analyzed whenever possible as it has previously been suggested that radon-associated lung carcinomas exhibit specific mutational patterns. The cumulative risk for lung carcinoma reached 11.0% based on 20 confirmed cases. Nine were small cell lung cancer (SCLC), whereas the expected frequency was 18%. The risk for malignant mesothelioma reached 2.5% based on 7 cases. The actuarial risk of malignant mesothelioma for patients given more than 20 ml Thorotrast was 7.8% compared to 1.4% for patients administered smaller amounts. Seven lung carcinomas and 5 malignant mesotheliomas were analyzed for p53 mutations; only 1 (in a lung adenocarcinoma) was detected. A possible association between Thorotrast and SCLC is suggested. In addition, a possible dose-response gradient exists for Thorotrast and malignant mesothelioma.
Adolescent↗
[Life changes after prolonged sick leave].
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Activities of Daily Living↗
[Bedside. The portable pencil computer for complete medical history taking in hospitals].
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Hospital Information Systems↗
NK-lysin, a novel effector peptide of cytotoxic T and NK cells. Structure and cDNA cloning of the porcine form, induction by interleukin 2, antibacterial and antitumour activity.
A 78 residue antimicrobial, basic peptide, NK-lysin, with three intrachain disulfide bonds was purified from pig small intestine and characterized. A corresponding clone was isolated from a porcine bone marrow cDNA library. The 780 bp DNA sequence had a reading frame of 129 amino acids which corresponded to NK-lysin. The clone was used to show that stimulation with human interleukin-2 induced synthesis of NK-lysin-specific mRNA in a lymphocyte fraction enriched for T and NK cells. Lower levels of mRNA were detected in tissues known to contain T and NK cells, such as small intestine, spleen and colon. Interleukin-2 also induced both proliferation of the lymphocyte fraction and cytolytic function in these cells. Immunostaining showed that NK-lysin was present in cells positive for CD8, CD2 and CD4. NK-lysin showed high anti-bacterial activity against Escherichia coli and Bacillus megaterium and moderate activity against Acinetobacter calcoaceticus and Streptococcus pyogenes. The peptide showed a marked lytic activity against an NK-sensitive mouse tumour cell line, YAC-1, but it did not lyse red blood cells. The amino acid sequence of NK-lysin exhibits 33% identity with a putative human preproprotein, NKG5, of unknown function but derived from a cDNA clone of activated NK cells. We suggest that NK-lysin is a new effector molecule of cytotoxic T and NK cells.
Amino Acid Sequence↗
An amphipathic helical motif common to tumourolytic polypeptide NK-lysin and pulmonary surfactant polypeptide SP-B.
The tumour-lysing and antimicrobial polypeptide NK-lysin and the pulmonary surfactant-associated polypeptide SP-B exhibit 24% residue identities (49% similarities), including six half-cystine residues in the same disulphide bonding pattern, and similar far-UV circular dichroism spectra corresponding to 45-55% alpha-helix and 20-25% beta-sheet structures. From this, we conclude that the conformations of NK-lysin and SP-B are similar. In contrast, the functional properties of the two proteins are dissimilar: SP-B does not exhibit antibacterial activity and NK-lysin does not significantly effect phospholipid spreading at an air/water interface. Saposins, which solubilize lipids and activate lysosomal hydrolases, the pore-forming amoebapores, and parts of acid sphingomyelinase and acyloxyacylhydrolase, also share 18-27% sequence identities with NK-lysin (and SP-B), including the six conserved half-cystine residues. The inclusion of NK-lysin extends the family of saposin-like polypeptides, all members of which appear to interact with lipids. Strictly conserved structural features with implications for helix topology and lipid interactions are observed.
1,2-Dipalmitoylphosphatidylcholine↗
Relative bioavailability of nicotine from a nasal spray in infectious rhinitis and after use of a topical decongestant.
The relative bioavailability of nicotine from a nasal spray was assessed in 15 smokers suffering a common cold and rhinitis according to generally accepted criteria. The patients were given a single dose of 2 mg nicotine from the nasal spray with and without concurrent administration of a nasal vasoconstrictor decongestant, xylometazoline, in randomised order. Control session measurements were made in the disease-free state. Applying strict bioequivalence criteria, we found that common cold/rhinitis slightly reduced the bioavailability of nicotine, both in its rate and extent; the geometric mean of the ratio of Cmax, AUC and tmax were 0.81, 0.93 and 1.36, respectively. The nasal vasoconstrictor, xylometazoline, normalised the extent of the bioavailability of nicotine, but further prolonged the time for absorption to almost twice that measured in the disease-free state, increasing the tmax ratio to 1.72. The results suggest that a minor proportion of people stopping smoking with the help of a nicotine nasal spray may experience a minor reduction in the effect of the spray during common cold/rhinitis. However, the nicotine self-titration behaviour found with most smoking cessation products (except the nicotine patch) will automatically lead to an adjustment of the dosage to achieve the desired effect.
Administration, Intranasal↗
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↗
Inhibition of kainic acid binding to glutamate receptors by extracts of Gastrodia.
S-(4-hydroxybenzyl)glutathione was isolated as the major principle responsible for the inhibition of the in vitro binding of kainic acid to brain glutamate receptors by water extracts of the plant Gastrodia elata. The affinity (IC50 value) of the compound is slightly lower compared to glutamate and glutathione.
Drugs, Chinese Herbal↗
Irradiation of bone metastases in breast cancer patients: a randomized study with 1 year follow-up.
The results from a prospective randomized trial comparing two different radiation schedules for treatment of painful bone metastases in women with recurrent breast cancer are presented. A total of 217 patients with painful bone metastases were randomized to either 30 Grey (Gy) in ten fractions, five fractions a week (5F/W) or 15 Gy in three fractions 2F/W. The effect of treatment was evaluated by pain assessment, the radiological response and the degree of side-effects. The patients were rated at start of treatment and after 1, 3, 6 and 12 months. No difference between the two radiation regimes was found, neither in achieved pain relief, improvement in level of activity and medication, nor was there any difference in radiological response and side-effects from treatment. Both regimes resulted in a significant improvement in both pain score and level of activity 1 month after treatment, an improvement which persisted during the follow-up period. We conclude that 15 Gy given in three fractions 2F/W is as effective as 30 Gy in ten fractions 5F/W, but more convenient to the patient and of less cost to society.
Adult↗
Ascorbate-induced free radical toxicity to isolated islet cells.
Ascorbate is known to be cytotoxic by generating free oxygen radicals, a property shared with the diabetogenic drug alloxan. Some reports indicate that also ascorbate may be diabetogenic. In this study the cytotoxicity of ascorbate on isolated mouse islet cells has been investigated. Ascorbate (0.5-2.0 mmol/l) induced a concentration-dependent increase of trypan blue uptake by the cells, indicating an increase of membrane permeability to the dye. Trypan blue uptake induced by 2.0 mmol/l ascorbate was inhibited by concomitant incubation of the cells with 200 mg/l superoxide dismutase, 200 mg/l catalase, 3.0 mmol/l cytochrome-c or 50 mumol diethylenetriaminepentacetic acid (DTPA), but not by 50 mmol/l D-mannitol. The results indicate that ascorbate is cytotoxic to islet cells by metal-catalysed free radical generation.
Alloxan↗
The accuracy of a high-precision digitizer for CAD/CAM of crowns.
An alternative method for manufacturing fixed prostheses that uses machine digitalization and a combination of milling and spark erosion has been developed. The digitizer used has a contact probe with a ball-shaped tip. This study evaluated the accuracy of the device and the transfer of data from the individual die to the computer. The dimensions of a square gauge as read by the machine were compared with the known dimensions of the object with a computer, which allowed determination of the accuracy of the digitalization. Procera machining and the implications for reliable prosthodontic treatment are discussed.
Analog-Digital Conversion↗
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↗