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Biomedical subjects

G Karlsson

Publications and source records attributed to G Karlsson.

At least 109 records · Page 6Linked to original sources
PubMed1991

IgG subclass deficiency with or without IgA deficiency.

IgG subclass deficiency (IgGSD) is difficult to define since reference materials vary between laboratories and the clinically relevant cut off levels for the various subclasses are not well known. The diagnosis of IgGSD should be based on more than one determination since the levels vary, due to various factors such as infections, operations, etc. There is a relation between IgGSD and occurrence of frequent infections, but at the same time even total lack of a subclass can be seen in healthy individuals. Infections in the upper and lower respiratory tract predominate. Gm allotypes influence IgG subclass levels. Most IgGSD patients are homozygous in the Gm system. Immunocytes producing IgG3 in the nasal mucosa correlate with serum IgG3 levels, whereas rectal IgG1 producing cells relate to serum IgG1 levels. This may reflect differences in antigen and/or mitogen exposure at the two mucosal sites. IgG2SD is the predominant form of IgGSD among children, whereas after puberty IgG3SD is most common. At the same age period there is a switch in sex distribution from three boys/one girl to one male/three females. Various abnormalities in B and T lymphocyte numbers and function are often found. In a double blind crossover study of Ig prophylaxis over 2 years in 43 IgGSD adult patients a significant decrease in the number of days with infections was seen both in the whole group and among the IgG1 deficient. Days with bronchial constriction were also significantly decreased among the 22 patients who had asthma as well. Acute bronchitis became significantly less frequent in the IgG3 deficient patients during Ig prophylaxis. This was seen in those under the lower range of 0.41 g/liter of Oxelius' early normal material, although many recent reference materials suggest 0.14-0.15 g/liter of IgG3 as the cut off. In a group of 25 consecutive patients with IgGSD + IgA deficiency recurrent respiratory infections were the major problem and lung function impairment was found in 12, and bronchiectasies in 5. Still many individuals with this combined deficiency have been reported to be healthy, again illustrating our limited understanding of these conditions.

Disease↗
PubMed1991

Isotype distribution of mucosal IgG-producing cells in patients with various IgG subclass deficiencies.

The subclass distribution of IgG-producing immunocytes was examined by immunohistochemistry in nasal and rectal mucosa of infection-prone patients with untreated IgG subclass deficiencies. Biopsy specimens from the two sites were obtained in 18 clinically and serologically well-characterized adult subjects; only a nasal or rectal sample was available from nine similar patients. Chronic lung disease was common in the patient groups with selective serum IgG1 deficiency and combined IgG1 and IgG3 deficiency, whereas the other categories of patients had mainly upper airway and other mild infections. Serum IgG2 or IgG3 deficiency was usually expressed also at the cellular level in rectal mucosa, and the proportion of rectal IgG1 cells was significantly correlated with the IgG1 level (r = 0.90, P less than 0.001). Likewise, there tended to be a decreased expression of the actual subclass at the cellular level in nasal mucosa of patients with serum IgG1 or IgG2 deficiency. Conversely, the median nasal proportion of IgG3 cells was remarkably unaffected by a deficiency of this subclass in serum and rectal mucosa. Interestingly, these patients rather tended to have raised IgG3 and reduced IgG2 cell proportions in their nasal mucosa, although this apparent local IgG3 compensation was nevertheless strongly correlated with the serum IgG3 level (r = 0.87, P less than 0.002). These disparities may reflect different antigenic and mitogenic exposure of the two tissue sites; for example, a persistent protein bombardment of the nasal mucosa that could conceivably override locally a B cell maturation defect. The possible clinical consequences of such variable mucosal expression of IgG subclass deficiencies remain to be studied.

Adult↗
PubMed1991

Macrophages on the nasal mucosal surface in provoked and naturally occurring allergic rhinitis.

Macrophages are the most common cell type residing in the lumen of the lower airways. However, very little is known about the presence and putative pathogenic implications of macrophages in the upper airways. Using specific immunohistochemical techniques, the presence of and changes in macrophage density were studied before and after allergen exposure in the laboratory and during natural allergen exposure of subjects with seasonal allergic rhinitis. The monoclonal antibody EBM 11 combined with the alkaline phosphatase-anti-alkaline phosphatase-technique was applied on cytospin-prepared slides. In the challenge experiment, 0.5 +/- 0.2% (mean +/- SEM; n = 10) of the total cell number were positive for the EBM 11 marker before challenge, thereby not differing from the controls (0.2 +/- 0.2%; mean +/- SEM; n = 3). Local allergen challenge induced an increase of these cells to a peak of 1.3 +/- 0.4% after 4 h (p less than 0.05). During seasonal exposure there was also a similar increase, from 0.7 +/- 0.2 to 1.3 +/- 0.3% (p less than 0.05; n = 11) in placebo-treated patients and from 0.7 +/- 0.2 to 1.6 +/- 0.4% (p less than 0.05; n = 11) in patients treated with topical glucocorticoids. There was, however, no direct relationship between nasal symptoms and number of macrophages present on the mucosal surface. The study indicates that macrophages are involved in the inflammatory processes of allergic rhinitis.

Adolescent↗
PubMed1990

CGP 35348: a centrally active blocker of GABAB receptors.

The biochemical, electrophysiological and pharmacological properties of the new GABAB receptor blocker CGP 35348 are described. In a variety of receptor binding assays CGP 35348 showed affinity for the GABAB receptor only. CGP 35348 had an IC50 of 34 microM at the GABAB receptor. The compound antagonized (100, 300, 1000 microM) the potentiating effect of L-baclofen on noradrenaline-induced stimulation of adenylate cyclase in rat cortex slices. In electrophysiological studies CGP 35348 (10, 100 microM) antagonized the effect of L-baclofen in the isolated rat spinal cord. In the hippocampal slice preparation CGP 35348 (10, 30, 100 microM) blocked the membrane hyperpolarization induced by D/L-baclofen (10 microM) and the late inhibitory postsynaptic potential. CGP 35348 appeared to be 10-30 times more potent than the GABAB receptor blocker phaclofen. Ionophoretic and behavioural experiments showed that GABAB receptors in the brain were blocked after i.p. administration of CGP 35348. This compound may be of considerable value in elucidating the roles of brain GABAB receptors.

Adenylyl Cyclase Inhibitors↗
PubMed1990

Characterization of the binding epitope of the monoclonal antibody DMAb-1 to ganglioside GM2.

Several derivatives of ganglioside GM2 were synthesized for mapping of the binding epitope of a monoclonal antibody raised against this ganglioside. The GM2 ganglioside was modified in both the hydrophobic and the hydrophobilic part of the molecule. The synthesized derivatives were characterized with fast atom bombardment mass spectrometry (FAB-MS). Affinity of the monoclonal antibody for the GM2 derivatives was determined by enzyme-linked immunosorbent assay (ELISA) on microtitre plates or by TLC immunostaining. Modifying the GM2 sialic acid by deacetylation or blocking of the carboxyl moiety abolished the binding to the monoclonal antibody while the cleaving of the glycol group on the sialic acid tail led to a 70% reduced binding affinity. Removal of the fatty acid (lyso-GM2) eliminated the binding to the antibody. GM2 derivatives with fatty acid moieties of 8 carbon atoms or less showed almost no reactivity. GM2 with saturated fatty acids 16:0, 18:0 and 20:0 had binding affinity similar to natural GM2, while the 24:0 fatty acid had only half the binding affinity. The results demonstrate the importance of ganglioside fatty acid composition with regard to ligand binding between the monoclonal antibody and its specific ganglioside antigen. Thus, caution must be shown in the application of immunaffinity methods with monoclonal antibodies for the quantitative determination of glycosphingolipids from different tissues.

Antibodies, Monoclonal↗
PubMed1990

The effects of baclofen and two GABAB-receptor antagonists on long-term potentiation.

The aim of the present study was to investigate whether activation or inhibition of GABAB receptors in hippocampal slices of rats has an impact on the synaptic plasticity in the CA1 area. Long-term potentiation (LTP) was induced by tetanic stimulation of the Schaffer collateral/commissural fiber tract and the responses of CA1 pyramidal neurons were recorded extracellularly. The increase in population spike amplitude after tetanic stimulation was taken as a measure of LTP. The selective GABAB receptor blockers phaclofen (1 mM) and CGP 35,348 (100 microM) facilitated the induction of LTP. Although baclofen (1 microM) reduced the population spike amplitude, it did not affect LTP. If, however, the stimulation voltage was increased to compensate for the baclofen-induced decline in population spike amplitude, LTP was facilitated. Under these conditions the induction of LTP was accompanied by the appearance of additional population spikes. In conclusion, GABAB receptors appear to exert a modulatory action on LTP.

Animals↗
PubMed1990

Ear discharge after insertion of transmyringeal tubes.

The peroperative bacteriology and cytology of the middle ear have been studied in 103 ears in 65 children operated on due to longstanding secretory otitis media. Within one month postoperatively, 12 ears (12%) showed signs of infection with discharge from the tube. Ten out of these 12 ears showed peroperative growth of Hemophilus influenzae, Branhamella catarrhalis, pneumococci or staphylococci in the middle ear effusions, a significant difference compared to ears without postoperative discharge. The peroperative cytological evaluation of the middle ear effusions from 10 out of the 12 patients with postoperative ear discharge showed presence of phagocytes as a sign of infection. It is concluded that pre-existing bacteria in the middle ear effusion of patients with longstanding secretory otitis media might increase the risk of postoperative infection within the first month after insertion of transmyringeal tubes.

Bacteria↗
PubMed1990

Cost-benefit evaluation of dental implants.

The growing evidence of the efficacy and effectiveness of dental implants calls for economic evaluations to determine the economic efficiency of this technology for different indications. Such studies must be integrated with the clinical evaluations in order to produce the relevant data. In most cases, dental implants will produce a better outcome than the best alternative technology, but this improvement will only come at greater cost. Cost-benefit evaluations of dental implants must therefore address the difficult task of assessing the value of the improvement in oral health.

Cost-Benefit Analysis↗
PubMed1990

Cytological and bacteriological aspects of secretory otitis media.

Bacteriological and cytological examinations were performed on 105 middle ear secretions from 66 children with middle ear effusion (MEE) of more than 3 months' duration. The secretions were searched for granulocytes and the activity of these cells was judged by their capacity for random locomotion and their ability to reduce nitroblue tetrazolium. The functional characteristics of the granulocytes were compared with the bacteriological findings on cultures from MEE. Bacteria commonly regarded as pathogens in middle ear infections (Hemophilus influenzae, Branhamella catarrhalis or Streptococcus pneumoniae) were found in 25% of the secretions. Granulocytes with activity or lacking activity, virtually dead, were found in all secretions where these bacteria were isolated. In secretions where bacteria commonly regarded as commensals, mainly staphylococci, were isolated, about two thirds of the secretions showed phagocytes with or without activity. No relation between bacterial growth and the functional state of the granulocytes was observed. In contrast, no phagocytes were found in over 60% of MEE lacking bacterial growth. These findings suggest a role for bacteria in the development and maintenance of secretory otitis media.

Child↗
PubMed1990

Luxation of the elbow complicated by proximal radio-ulnar translocation.

Luxation of the elbow complicated by proximal radio-ulnar translocation is a rare entity. The clue to diagnosis is the reversed position of the bones of the proximal forearm. In the a.p. projection the radial head articulates with the trochlea and the ulna with the capitellum. This unexpected anatomic relationship is easily overlooked. Delayed reduction may result in permanent impairment of elbow motility. Our experience with three recent cases is presented.

Child↗
PubMed1989

Inhibitory processes in normal and epileptic-like rat hippocampal slices: the role of GABAB receptors.

The purpose of this study was to obtain more insight into the role of GABAB receptors in the rat hippocampus using the selective GABAB blocker phaclofen. In the CA1 region in normal slices, phaclofen (1 mM) had no effect on population spike amplitude. Moreover, phaclofen did not affect paired-pulse inhibition when the paired-pulses were delivered at short interpulse intervals (20-30 ms). At longer interpulse intervals (50-150 ms) phaclofen moderately reduced paired-pulse inhibition. In slices treated with submaximal concentrations of bicuculline methiodide or penicillin, the frequency and amplitude of electrically induced multiple population spikes were not affected by phaclofen. The GABAB agonist baclofen, however, attenuated paired-pulse inhibition and this effect was antagonized by phaclofen. In the CA3 region, phaclofen reduced the inhibitory effect of baclofen on penicillin-induced burst discharges. In conclusion, although phaclofen antagonized the effects of baclofen it did not show proconvulsant activity. Furthermore, phaclofen did not induce any pronounced signs of disinhibition of hippocampal pyramidal cells as is usually seen with the GABAA receptor-blocker bicuculline methiodide.

Animals↗
PubMed1989

Trichophyton asthma: sensitisation of bronchi and upper airways to dermatophyte antigen.

12 adult patients with perennial asthma and chronic skin infection were found to have immediate hypersensitivity to Trichophyton spp. 10 patients were tested by bronchial provocation and gave immediate bronchial reactions to an extract of T tonsurans. Double-blind, placebo-controlled nasal challenge of 8 patients demonstrated that the upper airways of these patients were also sensitive to this dermatophyte antigen. In addition to perennial asthma most of the patients had persistent eosinophilia and chronic rhinosinusitis. The results suggest that absorption of fungal antigen can give rise to IgE antibody production, sensitisation of the airways, and symptomatic asthma and rhinosinusitis. Several patients had many of the features of late onset or "intrinsic" asthma.

Adult↗
PubMed1989

Late inhibitory postsynaptic potentials in rat prefrontal cortex may be mediated by GABAB receptors.

The GABAB antagonist phaclofen blocked the postsynaptic hyperpolarization induced by the GABAB agonist baclofen during intracellular recordings in rat cortical cells. This effect appears to be selective since responses to GABAA agonists (muscimol, THIP), GABA, 5-HT and L-glutamate were unaffected. Phaclofen also blocked synaptically evoked late inhibitory postsynaptic potentials (late IPSP). These results suggest that the late IPSPs in cortical neurons are mediated by GABA acting on GABAB receptors.

Animals↗
PubMed1989

Nasal mast cell response to natural allergen exposure.

A redistribution of mast cells into the epithelium and towards the mucosal surface was previously observed during the allergy season in individuals allergic to birch pollen. We have therefore attempted to investigate in greater detail the role of mast cells in mucosal allergy by the study of the morphological and biochemical changes that occur in the nasal mucosa of allergic individuals during natural allergen exposure. An activation of the intraepithelial mast cells was indicated by the observation of ultrastructural signs of a secretory activity. We also found that the normal strong correlation between mast cell numbers and histamine content in the nasal mucosa was absent in specimens taken during allergen exposure, which was interpreted as a result of a release of histamine from the mast cells with the appearance of a transient, non-mast cell pool of tissue histamine. Furthermore, the histamine content of the nasal mucosa during the pollen season was strongly correlated to the severity of symptoms experienced by the patients. These observations provide additional evidence that mucosal mast cells have a pathogenetic role in continuous allergic airway disease.

Allergens↗
PubMed1989

Natural allergen exposure does not influence the density of goblet cells in the nasal mucosa of patients with seasonal allergic rhinitis.

This double-blind, placebo-controlled group-comparative study in patients with seasonal allergic rhinitis was performed to investigate the possible influence of natural allergen exposure on the differentiation of goblet cells in the nasal mucosa. Furthermore, the effect of topical steroid treatment on such a putative influence was evaluated. Twenty adult patients with seasonal allergic rhinitis due to birch pollen were studied. Mucosal samples were obtained by scrapings before and during the pollen season and processed to evaluate the number of goblet cells/mm of intact epithelial lining. No statistically significant differences were found neither when comparing the number of goblet cells before and during the season nor when comparing the 2 treatment groups. In conclusion, the allergic inflammation could not be shown to accelerate the differentiation of goblet cells, and the beneficial effect of topical steroid treatment could not be explained by a prevention of increased goblet cell density.

Administration, Topical↗
PubMed1989

Nasal mucosal response to repeated challenges with pollen allergen.

In order to explore the dynamics of the cellular response of the airway mucosa to allergen exposure, controlled daily allergen challenges were performed for 7 days during the pollen-free winter months in nine patients with strictly seasonal allergic rhinitis caused by birch pollen allergen. Symptoms obtained after the challenge were related to morphologic changes within and on the surface of the nasal mucosa. Cell samples were obtained daily prior to challenge from the nasal mucosa using mucosal imprints on plastic strips, brush samplings from the nasal mucosa, and nasal lavage. For light microscopy, the cellular material obtained by brushing and nasal lavage were cytocentrifuged onto object slides. Histamine was measured in the cell pellets that were obtained using the lavage and brush procedures as well as in the lavage supernatant fluid. Four symptoms (sneezes, itching, secretion, and blockage) were recorded and expressed individually as well as in the form of a composite symptom score. Nasal blockage was measured using a nasal peak flow meter. The patients displayed an increase in nasal symptoms after the allergen challenge, which was further increased between Days 2 to 7 (p less than 0.05). The light microscopic evaluation of the lavage revealed an immediate increase in eosinophils from 2.3 to 13.1% and was maintained on the same level throughout the period of challenges. A similar increase was noted in the brush specimens, and a strong correlation was obtained between these two methods of sampling.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗