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Biomedical subjects

G Karlsson

Publications and source records attributed to G Karlsson.

At least 127 records · Page 7Linked to original sources

A brush method to harvest cells from the nasal mucosa for microscopic and biochemical analysis.

A method is described for the sampling of epithelial cells and other effector cells from the human airway mucosa for structural and biochemical analysis. The cell samples are obtained from the nasal mucosa using a small nylon brush which is rotated over the epithelium and soaked and shaken in a small volume of a balanced salt solution. Morphological evaluation using light microscopy and transmission electron microscopy revealed excellently preserved cytological detail. In asymptomatic individuals the cells harvested were as follows: 45 +/- 5.9% (mean +/- SEM) epithelial cells, 38 +/- 7.1% granulocytes, 16 +/- 2.3% large mononuclear cells (monocytes), and 1.3 +/- 2.3% eosinophils. Repeated measurements in the same individual revealed a coefficient of variation of the order of 40% for the proportions of cells harvested. In comparison with nasal airway lavage, a higher proportion of epithelial cells and monocytes were obtained with the brush method. The cells harvested could also be used for biochemical analysis. The histamine content of the cell pellets was found to be strongly correlated with the mast cell count (r = 0.93) and was estimated to about 10 pg/cell, which is higher than previously reported for mast cells obtained from human lung tissue dispersed by an enzymatic method. The present method appears to be appropriate for the study of cellular events in the nasal mucosal epithelium.

Adult↗

Dopamine D1- and D2-receptor interaction in turning behaviour induced by dopamine agonists in 6-hydroxydopamine-lesioned rats.

The selective dopamine D2-antagonist sulpiride potentiated contralateral circling behaviour induced by the D1-agonist CY 208-243 in rats with unilateral lesions of substantia nigra, but reduced the effects of the selective D2-agonist bromocriptine. Similarly, the D1-antagonist SCH 23390 tended to increase the effects of bromocriptine but markedly inhibited CY 208-243 induced turning. The mixed D1/D2-antagonist fluphenazine was effective in reducing circling behaviour induced by either agonist, whereas pimozide (D1/D2) inhibited only the actions of bromocriptine. These results indicate that the actions of CY 208-243 and bromocriptine are mediated via distinct but interacting receptor subtypes.

Animals↗

Phenotypic expression of proteoglycan in mast cells of the human nasal mucosa.

The phenotypic expression of the proteoglycan of human mast cells in the nasal mucosa and normal skin was analysed using histochemical techniques. Nasal mucosa was obtained from normal subjects, from patients with seasonal allergic rhinitis before and during the pollen season and from patients with nasal polyps. In the latter groups, specimens were taken from both polyp tissue and adjacent nasal mucosa. Formaldehyde treatment blocked the cationic dye binding in 75-84% of the mast cells located in the nasal mucosa, as compared to the optimum fixation with IFAA (iso-osmotic formaldehyde-acetic acid). A significantly lower degree of blocking of dye binding was obtained in the human skin where 45% of the mast cells were susceptible to formaldehyde treatment (P less than 0.01). The mast cells of the polyp tissue also showed a relatively low degree of blocking (54%), which was significantly lower than the blocking of mast cells of the nasal mucosa taken from the same individuals (P less than 0.05). Staining of serial tissue sections in Alcian Blue containing graded concentrations of MgCl2 was used to determine the critical electrolyte concentration (CEC) of the dye binding, defined as the salt concentration at which the staining of 50% of the mast cells is extinguished. The CEC of the skin mast cells was 0.64M MgCl2 which is significantly higher than that of the mast cells of the nasal mucosa of normal subjects [0.49M (P less than 0.05)], allergic subjects [0.52M (P less than 0.01)], patients with polyp disease [0.52M (P less than 0.01)] and the polyp tissue proper [0.57M (P less than 0.05)].(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The cellular response of the human allergic mucosa to natural allergen exposure.

It has been suggested that the IgE-dependent late-phase reaction to allergen exposure, with the features of an inflammatory cellular infiltration and airway hyperreactivity, is a link between anaphylaxis and continuous allergic airway disease. Our main knowledge of the cellular response to allergen in sensitized individuals has been derived from allergen-challenge models. To explore the dynamics of the cellular response during the actual disease, patients with a strictly seasonal allergic rhinitis were studied during natural allergen exposure. Ten patients suffering from an isolated birch-pollen allergy were followed from a symptom-free state before, during, and to the height of the birch-pollen season. Repeated parallel cell samplings from the nasal mucosa were performed with cytologic imprints on plastic strips, nasal lavages with the recovery of the cells in the lavage fluid with cytocentrifugation on object slides for cytologic study, and scrapings from the nasal surface with a curette for histologic and ultrastructural evaluation. The histamine content was determined in lavage fluid and cell pellets. The tosyl-alpha-tosyl-L-arginine methyl esterase activity of the nasal lavage fluid was also determined as a biochemical marker of the allergic inflammatory reaction. The birch-pollen season was moderate in terms of pollen counts, and this resulted in mild to moderate nasal symptoms that ran parallel to the birch-pollen counts. The total number of cells recovered in the lavage fluid was 1.2 +/- 0.4 (SEM) x 10(6) before and 3.2 +/- 2.0 per 10(6) cells (not significant) during pollen exposure. Most cells were neutrophils and mononuclear cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Secretory activity of nasal mucosal mast cells and histamine release in hay fever.

Although theoretical considerations and experimental evidence implicate the mast cells in the pathophysiology of the immediate type hypersensitivity reaction, the evidence of their active participation in human allergic disease is still fragmentary. We have therefore sought evidence of mast cell activation in allergic mucosal disease using strictly seasonal allergic rhinitis as a model. Twelve patients with birch pollen-induced hay fever were examined before and well into the birch pollen season. Allergen exposure was monitored by pollen counts and the degree of symptoms registered daily. Small surgical biopsies and mucosal imprints were obtained from each patient before and during the season. Mast cells were analysed by light and electron microscopy and mucosal histamine was measured using a sensitive HPLC assay. We found a reduction in the number of mast cells in the nasal mucosa during pollen exposure (p less than 0.05) but no significant reduction of the histamine content. There was a correlation between the nasal mucosal mast cell density and histamine content before the pollen season (r = 0.76; p less than 0.01), but no such correlation was found during the period of pollen exposure (r = 0.19; n.s.). This finding points to secretory activity by the mast cells during the pollen season and to the appearance of a non-mast cell pool of tissue histamine. Evidence for a secretory activity of the mast cells during the pollen season was also confirmed by electron microscopy. In addition, we found a strong correlation (r = 0.77; p less than 0.01) between the histamine content of the nasal mucosa during the pollen season and the degree of nasal symptoms. The number of epithelium-associated mast cells found on mucosal imprints prior to the pollen season showed a strong correlation with the symptoms experienced later during the period of pollen exposure (r = 0.83; p less than 0.01). Taken together these observations indicate that the mast cell has a pathogenetic role in continuous allergic airway disease and re-emphasizes the role of histamine in the induction of the symptoms of allergic rhinitis.

Adult↗

Methods for obtaining specimens from the nasal mucosa for morphological and biochemical analysis.

The nose is the part of the airway system which is most easily accessible for morphological and pathophysiological evaluation of changes occurring as a response to various stimuli. During recent years several new atraumatic techniques for harvesting cells for morphological and biochemical analysis have been introduced, in addition to the more well known surgical biopsy procedures and nasal smears. Such techniques include nasal lavage, scrapings from the nasal mucosa, brush techniques and imprints. Several of these techniques allow repeated samplings, obtaining quantitative as well as qualitative information as to the cells present on the surface of, as well as within, the epithelial lining of the nasal mucosa. Some techniques provide the investigator with a method for obtaining information on the cellular content of certain biochemical markers such as histamine. The present review describes the merits and disadvantages of the old and new methods and provides guidelines as to when each method should be considered.

Biopsy↗

Humoral immunity in nasal mucosa of patients with common variable immunodeficiency.

Humoral immunodeficiency, as reflected by the low serum immunoglobulin (Ig) concentrations in adult patients with common variable immunodeficiency (CVID), was even more severely expressed at the B-cell level in their nasal mucosa. No Ig-producing cells could be detected by immunohistochemistry in 11 of 19 mucosal specimens. The epithelial distribution of secretory component (SC) was normal in all specimens, but a sign of SC-dependent IgM transport was seen in only three. Epithelial IgA was completely lacking. All patients had had recurrent lower respiratory tract infections and 16 had recurrent or chronic infections of the upper respiratory tract. A previous report indicated that the intestinal mucosa is a privileged site for maturation of B cells in patients with CVID; the present study shows that this does not hold true for the nasal mucosa. This difference in B-cell maturation may in part explain the preferential susceptibility to infections in the respiratory tract of patients with CVID.

Adolescent↗

Proteinase activity in effusions from children with otitis media with effusion.

Proteinase activity has been demonstrated in middle ear effusions from patients suffering from otitis media with effusion. Proteinase activity was characterized by various biochemical, chemical and physical parameters. Chelators and sulfhydryl group reacting substances reduced the enzyme activity. Enzyme activity was positively correlated to the number of granulocytes present in the effusion. No correlation to bacteriological findings or to tympanic membrane status was seen and the proteinase activity showed wide ranges within different categories of middle ear effusions.

Child↗

Immunoglobulin G subclass deficiencies.

Low levels of single or multiple serum immunoglobulin G (IgG) subclasses is a common finding among patients with increased susceptibility to infections. In this investigation we summarize data from studies of 503 subclass-deficient individuals. Low IgG2 levels was the most common deficiency among children, and boys were more often deficient than girls. From the age of 16, females dominated, and the most frequent finding was low IgG3 levels. In vitro T or B lymphocyte dysfunction was demonstrated in 75% of the individuals, suggesting that low subclass levels may be indicators of an underlying defect at the B cell or possibly T cell level. Vaccinations and mucosal biopsies were performed to evaluate which patients may be helped by immunoglobulin substitution therapy.

Adult↗

Immunohistochemical study of nasal mucosa in patients with common variable immunodeficiency.

The presence of immunoglobulin (Ig)-producing cells was studied immunohistochemically in nasal mucosa obtained from adult patients with common variable immunodeficiency. In 11 of 19 biopsy specimens no such cells could be detected and with one exception very few appeared in the others. Distinct sign of epithelial IgM transport mediated by secretory component (SC) was seen in three specimens although the epithelial distribution of SC appeared normal in all cases. All patients had recurrent lower respiratory tract infections and 16 had recurrent infections of the upper respiratory tract. The localization of the infections primarily to the respiratory tract might be explained by the fact that the immunodeficiency, as reflected by the low serum Ig concentrations, was still more severely expressed at the B cell level in the nasal mucosa.

Adolescent↗

Immunohistochemical study of nasal mucosa in patients with selective IgA deficiency.

Fifteen nasal biopsy specimens from adult patients with selective IgA deficiency were examined in a 'blind' immunohistochemical study for the presence of immunocytes producing various immunoglobulin (Ig) classes. Three groups of patients could be identified. One group had a predominance of IgG- and IgM-producing cells in their nasal mucosa, a second group revealed mainly IgG- and IgD-producing cells, and a third group had very few mucosal immunocytes. The clinical examinations showed that upper respiratory tract infections were most common in patients with few immunocytes while such infections were least common in patients with predominance of IgG and IgM immunocytes. Our results indicated that IgM, in contrast to IgD, acts as a compensatory secretory Ig in some patients with selective IgA deficiency.

Adolescent↗

The clinical condition of IgA-deficient patients is related to the proportion of IgD- and IgM-producing cells in their nasal mucosa.

Nasal biopsy specimens from 15 adult patients with selective IgA deficiency but normal IgG-subclass levels were examined by immunohistochemistry for the presence of immunocytes producing various Ig isotypes. The mucosal samples were completely IgA-deficient except in two cases where 0.9% and 8.4% IgA cells were found, respectively (normal, 69.8%). Numerous IgG- (mainly IgG1-) producing cells were present in 10 samples; in five of these there were additional IgM- but virtually no IgD-producing cells, whereas in the other five a marked dominance of the IgD over the IgM isotype was seen. The latter category of patients had more upper airways infections (recurrent acute rhinosinusitis, otitis media, and tonsillitis) than the former, who had no recurrent upper respiratory tract infections except one patient with recurrent acute rhinosinusitis. The five remaining samples, which contained very few Ig-producing cells, were derived from patients with even more frequent infections than those showing IgD predominance. Our results indicate that IgM acts as a compensatory secretory Ig in the upper respiratory tract of some IgA-deficient subjects. However, immunoregulatory events favouring local IgD responses apparently do not support mucosal defence satisfactorily, either because local production of IgM is hampered or because IgD (which is not a secretory Ig) blocks complement-dependent reactions mediated by IgG and IgM antibodies within the mucosa.

Adolescent↗

The relative change in saliva secretion in relation to the exposed area of the salivary glands after radiotherapy of head and neck region.

Sixty patients, 37 women and 23 men, were examined in a prospective study to demonstrate the relative change in saliva secretion after the patients had undergone radiotherapy in the head and neck region. By using VAS (Visual Analogue Scales) for the assessment, clinical intra-oral changes in the body tissue have, hopefully, not influenced the results. In this investigation, the post-radiological saliva secretion was put in relation to the preradiological secretion, as well as to the location of the tumour, irradiation dosage, extent of irradiated area and the pairs of big salivary glands. In the overwhelming number of these patients, the reduced saliva flow rate should be classified as hyposiali (0.1-1.0 ml/15 mins) and less frequently as xerostomi (0.0-0.9 ml/min). It is discussed in this paper whether it would be possible to protect, radio treatment permitting, for example the mandibular glands from irradiation in patients with maxillary tumours, by having odontology supply mouth fixtures, allowing for the maximum opening of the mouth during the irradiation part of the treatment. This would make it possible to move the mandible out of the irradiation area without interfering with radiotherapy. By cooperating with the oncology team in a trusting way, we could contribute with an improved life quality after therapy for patients with tumours in the head and neck region.

Adult↗

Substance P and human nasal mucociliary activity.

Substance P (SP), a potent inflammatory agent, has been found in sensory nerve fibres in the nasal mucosa in several experimental animals as well as in man. It may participate in the inflammatory response as part of the mucosal defence against foreign materials. In experimental animals SP has been found to increase mucociliary in airway mucosa. The present study was performed in order to find out the relationship between topically applied SP and nasal mucociliary function in humans. Thirteen healthy volunteers were challenged with 65 micrograms SP or placebo in a randomized cross over fashion and mucociliary transport time was determined each time using the saccharine dye test. The dose of SP was chosen after an open dose-response study. No statistically significant change in the mucociliary transport time was found after challenge with SP as compared to placebo. The possible reasons for this are discussed.

Adult↗