Histamine release from blood cells and serum ECP in patients with asthma, during and after a mild pollen season.
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Asthma↗
Biomedical subjects
A Davidsson
Publications and source records attributed to A Davidsson.
Influenza specific serum IgE is present in non-allergic subjects.
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Humans↗
Apoptosis and phagocytosis of tissue-dwelling eosinophils in sinonasal polyps.
OBJECTIVE: Sinonasal polyps contain numerous tissue-dwelling eosinophils, but the mechanisms causing their accumulation, functional activities, and resolution are largely unknown. STUDY DESIGN: Nasal polyp tissue from 14 patients was evaluated for cellular expression of CD95, CD68, and annexin-V, for the degree of apoptosis, and for phagocytosis of eosinophils. MATERIAL AND METHODS: Histological sections were immunostained as single stains for CD95, CD68, and annexin-V, and as an immunostaining for CD68 combined with a modified Vital New Red staining. The latter staining is specific for eosinophils. Other sections were stained by terminal d-UTP nick end labeling (TUNEL) assay and routinely stained for H&E. Evaluation of the amount of stained cells was performed by counting the average number in 10 randomly chosen high-power fields. The TUNEL positivity was in all cases confirmed with apoptotic morphology. RESULTS: The inflammatory infiltrate consisted of numerous eosinophils but also a considerable amount of lymphocytes, mast cells, and macrophage-like CD68+ cells. CD95 was frequently expressed on eosinophils, on numerous other inflammatory cells, and also on morphologically apoptotic cells. annexin-V-positive eosinophils were not as frequent as CD95+ cells, but numerous annexin-V-positive eosinophils were found. CD68+ cells approximately equalled the number of eosinophils. The number of cells phagocytosing eosinophils varied between polyps. Apoptosis of eosinophils (as evaluated by TUNEL combined with apoptotic morphology) was a common finding in six of the polyps. CONCLUSIONS: Previous in vitro and ex vivo findings of CD95 on eosinophils are now supported by demonstration of CD95 on eosinophils in this in vivo study. This investigation revealed a switch of the membrane-bound phosphatidylserine of apoptotic cells, which is a novel observation. The study has demonstrated apoptosis of tissue-dwelling eosinophils, and that CD68+ macrophage-like cells phagocytose eosinophils within the sinonasal polyps.
Annexin A5↗
Is elective hernia repair worthwhile in old patients?
OBJECTIVE: To find out if elective herniorraphy in patients aged 75 and over is worthwhile. DESIGN: Retrospective study. SETTING: District hospital, Sweden. SUBJECTS: 146 consecutive patients aged 75 years or more, who had their hernias repaired during the period 1992-95. MAIN OUTCOME MEASURES: Patient satisfaction measured by a five-point analogue scale. Clinical and personal details, morbidity, mortality, and surgical variables were obtained from case records. RESULTS: Community social service was not required by 114 (78%) of the patients and 15 (22%) had no preoperative complaints. Our patients rated their satisfaction with their choice to have an operation, as well as its effect on their preoperative symptoms as 4.9. Emergency operations (p = 0.02), femoral hernias (p = 0.01) and direct inguinal hernias (direct:indirect ratio 0.81) were more common in this age group. Femoral and direct inguinal hernias tended to recur more often than usual. Emergency operation, dementia, and diabetes were associated with a reduced short-term survival. CONCLUSION: Elective hernia repair in an elderly population is highly appreciated by the patients, and worthwhile. If coexisting disease and domestic arrangements are controlled, the patients' need for hospital care can be minimised. Mesh is recommended in femoral and direct inguinal hernias, which were associated with an increased reoperation frequency. A more vigilant protocol of indications for hernia surgery in the aged may minimise the need for both emergency and unnecessary operations.
Aged↗
Metallothionein and Fas (CD95) are expressed in squamous cell carcinoma of the tongue.
Metallothionein (MT) is a chelator present in myoepithelial cells, whilst the Fas-receptor (APO-1, CD95) has been described primarily in human T Jurkat cells. 20 cases of carcinoma of the tongue were investigated immunocytochemically with regard to MT, Fas and Bcl-2. In normal oral squamous epithelium, MT is located in the basal/parabasal dividing cells only. In well-differentiated nests of carcinomas, MT is observed almost entirely in peripherally located cells. In situ end-labelling indicates apoptosis in the centre of these nests, but not in the peripheral areas. Less-differentiated areas show more general MT-positivity, but little apoptosis. All 24 tumours are Fas-positive, but normal epithelia are mainly negative (P < 0.0001). Bcl-2 protein was sparse in the tumours compared with MT and Fas (P < 0.0001). We thus suggest that MT, possibly due to its chelating properties, may contribute to delaying cells entering apoptosis, both in normal epithelium near the base and in less-differentiated regions of carcinoma. Moreover, Fas may be present in cells of human malignancies, as well as those of established malignant cell lines.
Apoptosis↗
Bcl-2 immunoreactivity in salivary gland neoplasms is unrelated to the expression of mRNA for natural killer cell stimulatory cytokines interleukin (IL)-2 and IL-12.
Certain cytokines are involved in the generation of natural killer (NK) cells and participate in the regulation of the proto-oncogene bcl-2. We aimed to study the mRNA expression of interleukin (IL)-2, IL-4 and IL-5, the composition of the tumour infiltrating lymphocytes (TIL), and the expression of bcl-2 in 14 benign and malignant human parotid tumours. T IL were predominantly composed of T lymphocytes and NK cells. We found evidence for the homing of T cells, and for generation of NK cells in the vicinity of the tumours. mRNA for IL-2 and IL-12, were identified but IL-4 mRNA was not found. The cytokine profiles and the composition of TIL of the two tumour categories were indistinguishable, suggesting that these host-response variables do not explain the differences in biological behaviour of these particular tumours. The results support a shift towards Th 1 (T helper 1) cells and interferon-gamma production, and that IL-12 also in vivo may play an important role in the regulatory interaction between innate resistance and adaptive immunity in tumour diseases. Most infiltrating lymphocytes showed strong expression of bcl-2; an interesting observation with regard to lymphocytic apoptosis in neoplastic diseases. The immunoreactivity for the bcl-2 protein varied considerably between and within tumours, and almost all benign tumours showed strong bcl-2 positively whereas several of the malignant tumours showed weak or absent staining. The variable expression of bcl-2 protein suggests a different susceptibility of tumour cells to apoptosis. The results also indicate that bcl-2 cannot pla a major role as protective agent in the specific apoptotic pathway induced by NK cells.
Humans↗
Positive identification in situ of mRNA expression of IL-6, and IL-12, and the chemotactic cytokine RANTES in patients with chronic sinusitis and polypoid disease. Clinical relevance and relation to allergy.
Interleukins 6 (IL-6) and 12 (IL-12), and the chemoattractant chemokine RANTES were studied in ethmoidal mucosa, using reverse transcriptase polymerase chain reaction. The 49 patients had chronic sinusitis or nasal/paranasal polyposis, and some also allergy. To the best of our knowledge, this is the first study that demonstrates RANTES and IL-12 on mRNA level in human sinonasal mucosa in situ. mRNA for IL-6, IL-12 and RANTES were detected in 2, 8 and 6 patients with chronic sinusitis, respectively, and in mucosa from patients with polyposis a positive expression was observed in 4, 14 and 10 cases. There were no statistically significant differences. Analysing the entire group of 49 patients, disregarding type of mucosal disease, the number of patients with positive RANTES was significantly higher than that for IL-6. Similarly, IL-12 positivity was more frequently expressed than IL-6. mRNA for IL-6 was expressed in only 2 of the allergic patients. The cytokine production studied thus seems to be unrelated to the clinically defined entities. There is thus a local production in human diseased sinonasal mucosa of RANTES, as well as of IL-6 and IL-12. The local production of RANTES is an important prerequisite for recruitment and migration of inflammatory cells into the tissue. IL-12 is a co-stimulator of antigen-specific responses of established T helper 1 (Th1) clones, and regulates the responsiveness of the clones to a number of T cell growth factors. The study supports a shift towards Th1 cells in these disease entities.
Adjuvants, Immunologic↗
Nasal messenger RNA expression of interleukins 2, 4, and 5 in patients with allergic rhinitis.
In nasal biopsies from 17 adult patients with seasonal allergic rhinitis and from 10 healthy controls, cytokines were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR). The time-course study during winter included repeated local allergen provocation with subsequent nasal biopsies as well as biopsies taken during pollen season. The RT-PCR for CD44 yielded positive bands in 65 of 71 cases, in which cases mRNA for interleukins 2, 4, and 5 (IL-2, IL-4, and IL-5) were thus investigated by means of seminested PCR. IL-4 mRNA was found almost exclusively in the allergic patients. During provocation a significant increase in IL-4 was noticed compared with controls (p = 0.043). Equally, during the natural pollen season, IL-4 mRNA expression was significantly higher in patients not using nasal corticosteroids compared with those who did (p = 0.011). No differences in IL-2 or IL-5 were observed between the groups. These findings also indicate, together with earlier observations of T-cell activation, a phenotype switch toward T-helper 2 (Th2) cells, and the accumulation (homing) of these T cells in the nasal mucosa, that T cells constitute the main source for IL-4 in the nasal mucosa. Therefore, allergic patients have an increased synthesis of IL-4 when provoked with the allergen, and during natural pollen season this synthesis can be downregulated by corticosteroids. Furthermore, this study exemplifies the versatility of molecular biology in surgical pathology and that even low-copy-number cytokine mRNA can be examined in routinely snap-frozen surgical specimens.
Adult↗
Quantitative computerized image analysis of immunostained lymphocytes. A methodological approach.
A methodological approach by computerized image analysis to quantify immunostained objects in histological sections is described. We have investigated antibodies against CD4, CD8, CD20, CD23 and CD25 in frozen sections of human nasal mucosa; however, the methodology of standardization is of general validity. The study was designed particularly to investigate the following points: 1) light intensity, 2) the grey level for counter staining intensity, 3) the grey level threshold value for positive objects, 4) the minimal acceptable size of a positive object, 5) the influence of the brightness of the light on both the number and the area of objects. Furthermore, random sampling and determination of 6) the area per section, and 7) the number of histological sections to be measured per biopsy. Finally, a study of reproducibility of immunostaining intensity was performed. The influence of the different parameters mentioned above was studied and the values (eg. threshold value) for our particular setting of microscope, image analysis equipment, computer software etc, were defined. The method was then tested for intra- and interindividual variation which was found to be less than 5%. Correlation analysis of the reproducibility gave coefficients of correlation of 0.99, both concerning number of immunopositive objects and immunopositive area. We emphasize the importance of a highly standardized methodology if the numeric data obtained from computer assisted image analysis are to be more accurate than semiquantitative assessments by experienced observers. With a thorough standardization as described in this method it is possible to obtain numeric values, and data with low deviations, which are two obvious and important advantages.
Antigens, CD↗
Allergen-induced changes of B-cell phenotypes in patients with allergic rhinitis.
We investigated sub-populations of B-lymphocytes in nasal mucosa and peripheral blood of 17 patients with seasonal allergic rhinitis (birch pollen) and 10 controls. The study included provocation with allergen during the non-pollen season, during which no participant used medication. Samples were also taken during the pollen season. Subsets of B-cells as expressed by different CD antigens were investigated by immunohistochemistry on frozen sections and by flow cytometry of peripheral blood. Nasal CD23+ B-cells decreased in allergic patients during provocation, indicating that mature virgin CD23+ B-cells switch into a memory B-cell phenotype with loss of CD23 expression. This indicates differentiation towards cells that can represent a local source for IgE synthesis. No decrease was observed during the pollen season when the patients used medication. Serum IgE was significantly higher in allergic patients on all occasions. The observed up-regulation of CD40 expression on peripheral blood B-cells in allergic patients during the pollen season clearly indicate B-cell activation. Furthermore, a relative increase of CD19+ B-cells was observed in peripheral blood during provocation. Upregulation (by IL-4) of CD40 on B-cells which then may be stimulated by gp39 (CD40 ligand) can constitute an early and important event in the IgE-mediated allergic reaction.
Adult↗
Increase in CD4+ and CD45RO+ memory T cells in the nasal mucosa of allergic patients.
By means of immunocytochemistry we have investigated subsets of T lymphocytes in frozen sections of nasal mucosa from patients with seasonal allergic rhinitis and healthy control persons. All participants were subjected to time-course provocation during the non-pollen season, and samples were taken during provocation as well as during the natural pollen season. Computerized image analysis was applied for evaluation of the immunostained lymphocytes. CD45RO+ memory T cells outnumbered the remaining leukocyte populations in the mucosa of both allergic patients and controls on all occasions. During the repeat provocation there was no difference in numerical values, with respect to any of the five leukocyte subpopulations studied (CD4, CD8, CD25, CD45RA and CD45RO), between patients and controls. However, during continuous exposure in the pollen season a significant increase in CD4+ cells was observed in allergic patients compared to before provocation (p < 0.05). No changes were observed with respect to CD8+ and CD25+ cells. Similarly, an increase in CD45RO+ memory was found in allergic patients during the pollen season compared to the non-pollen season (p < 0.02). This latter finding was, however, only evident in the patients who did not use nasal corticosteroids. Hence the present investigation has demonstrated an allergen-induced increase in CD4+ and CD45RO+ memory T cells in the mucosa of allergic patients during the pollen season. These events may constitute a cellular basis for local continuous production of certain cytokines, particularly interleukin-4, which is essential for IgE synthesis.
CD4-Positive T-Lymphocytes↗
Malignant melanoma of the ear.
This paper reports on 16 cases of primary malignant melanoma of the external ear and the patients were followed up for two to 116 months. Fourteen patients had surgical excision with wide margins as initial treatment, whilst two had an amputation performed. Eleven patients had no recurrences, two died of other diseases, and four died of malignant melanoma. The five patients who developed recurrences received further surgery and two also radiotherapy. Seven of the cases were histologically of the nodular type, six were superficial spreading, two were in situ melanoma, and one was a lentigo maligna. The thickness ranged from 0.15 to 11.5 mm. Classification according to Clark et al. (1969) revaled that as many as nine cases were Clark level IV or more. Immunostaining with PCNA yielded strong positivity in all cases, however, statistical analysis did not reveal any differences that could be correlated to the prognosis. Estimation of the vascularization at the base of the tumours by means of immunostaining with CD31 did not reveal any significant differences either. We concluded that in our material the thickness of the tumour is of greater prognostic value than the estimation of proliferation by PCNA and vascularization by CD31. The value of PCNA and CD31 as possible prognostic parameters needs to be evaluated in a larger series. It is emphasized that malignant melanoma of the external ear is a highly malignant tumour, and that four of our 16 patients died of their disease, three of them within a year after diagnosis. Malignant melanoma of the external ear is readily inspected and thereby an early diagnosis should be possible.
Adult↗
The so-called 'allergic' nasal polyp.
A series of 95 consecutive patients who have had a polypectomy was investigated with regard to clinical history and the morphology of the polyps. The results were compared with a series of 203 patients with allergy, of whom 12 had been polypectomized. The study revealed that a high percentage of the 95 patients had subjective complaints, particularly nasal congestion, nasal discharge, sneezing, headache, snoring and a loss of smell. The latter was present in nearly 58% of the patients, and persisted long after the operation in a third of the cases. More than 50% of the 95 patients had had 3 or more polypectomies. Rather few patients suffered from allergy-like conditions. Eighty-two of the 95 polyps were of the ordinary, oedematous, eosinophilic type; 7 were neutrophilic, fibro-inflammatory; 5 showed pronounced hyperplasia of the seromucinous glands, and 1 was a so-called polyp with atypical stroma. Only 6% of the 203 patients with allergy had had a polypectomy. Ten of the 12 polyps removed from the series of patients with allergy were of the ordinary type and 2 of the fibro-inflammatory type. A review of the literature is done concerning the association between nasal polyp and different diseases. The results of the present study support the concept that allergy is not the only cause for nasal polyps and that the accumulation of eosinophilic granulocytes observed in most polyps is often not related to allergy.
Adult↗
Activated T cells in the nasal mucosa of patients with grass-pollen allergy. A pilot study.
Six patients with grass-pollen allergy were provoked with water-soluble grass pollen until a pronounced allergic reaction occurred. This was performed outside the grass-pollen season, and the allergen was administered on the edge of the inferior turbinate. Biopsies were taken both before provocation and during the reaction, 15-30 minutes after provocation. The nasal population of immunohistochemically positive cells for HLA-DR, CD1, interleukin-2-receptor, IgE, CD4 and CD8 were studied. There was a marked increase of IL2-R-positive cells (activated T lymphocytes) in the nasal mucosa after provocation, whilst the other cell populations approximately remained unchanged (apart from a certain increase of IgE). The increase of activated T lymphocytes may imply that certain subsets of T cells play a role in the allergic response, and that the role of helper T cells very likely is much more complex than the regulation of mast cells and eosinophils. The concomitant presence of Langerhans' cells (CD1-positive) and activated T lymphocytes may indicate a possible association on site between an antigen-presenting cell and both effector as well as memory cells in allergic reactions.
Allergens↗
Aberrant intratympanic internal carotid artery: a potentially hazardous anomaly.
A case is presented of a 3-year-old girl with no previous history of ear disease or developmental defects who bled profusely upon (right) myringotomy. The haemorrhage could only be stopped with the aid of an ear insert and a nasopharyngeal balloon catheter. The balloon catheter was removed the following day but the girl had to use an ear insert for a total of 76 days following myringotomy because of repeated haemorrhage from the ear. The subsequent investigation using CT and angiography revealed an aberrant internal carotid artery in the middle ear. It is concluded that the one most important factor in the handling of these cases is to be aware of the existence of aberrant internal carotid arteries and to have a high degree of suspicion when encountering any abnormal clinical or radiological findings which might point in the direction of vascular abnormalities. The failure to detect this condition before any surgical intervention on the affected ear can have disastrous consequences. The method of choice in handling these cases is one of avoidance of middle ear manipulation in order not to cause haemorrhage from the aberrant artery.
Carotid Artery, Internal↗
Electronic transitions in the isoalloxazine ring and orientation of flavins in model membranes studied by polarized light spectroscopy.
The orientation of flavin mononucleotide (FMN) in model membranes and the directions of the transition moments of the first three bands in the electronic absorption spectrum of the oxidized form of the isoalloxazine ring have been determined by means of linear dichroism and polarized fluorescence spectroscopy. Measured counterclockwise relative to the axis connecting the two nitrogens in the central ring (considered positive when going in the direction from -CN less than to greater than or equal to N), these angles are 58 +/- 4 degrees (450-nm band), 97 +/- 3 degrees (350-nm band), and 119 +/- 2 degrees (260-nm band).
Chemical Phenomena↗
Quantitative assessment and repeatability of chlorine in exhaled breath condensate.
BACKGROUND: Airway condition is presumably reflected in epithelial lining fluid (ELF). Exhaled breath condensate (EBC) has been used as a surrogate marker of the composition of ELF. OBJECTIVES: This study aimed at assessing the technical repeatability of chlorine measurements in EBC and comparing two separate condensators (Ecoscreen and R Tube regarding recovery and repeatability. Furthermore, the association between condensate recoveries and variations in the airway status were scrutinized. METHODS: EBC was collected using two condensators from 10 healthy volunteers. In addition, 13 asthmatic patients produced EBC with or without an added resistance of 5 cm H2O (Res5), applied to the outflow tract of Ecoscreen. All tests were done in random order. Chlorine levels (analyzed by a coulometric technique) in EBC served as a tool for investigation. RESULTS: Chlorine was measurable in all samples. The coefficient of repeatability of chlorine measurements was <10%. Chlorine levels were higher in EBC obtained from R Tube (p < 0.001), and differences in recoveries and variability in chlorine levels were presumably related to technical differences in the condensators and not to the repeatability of chlorine measurements per se. Air-flow-dependent chlorine levels were obtained from healthy volunteers. Application of Res5, recruiting additional alveoli, resulted in increased recovery of the EBC volume, but not of chlorine, from those that had the most pronounced airway obstruction (p = 0.05). CONCLUSION: We conclude that by employing a sensitive analysis technique, chlorine is repeatedly measurable in EBC. We suggest that the bulk of chlorine in EBC originates from large airways and not from the alveolar area. Both condensators were comparable regarding repeatability but differed regarding chlorine recovery.
Adult↗