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M G Karlsson

Publications and source records attributed to M G Karlsson.

36 records · Page 2Linked to original sources
PubMed1997

No association between immunohistochemical expression of p53, c-erbB-2, Ki-67, estrogen and progesterone receptors in female papillary thyroid cancer and ionizing radiation.

An association has previously been reported between exposure to medical diagnostic ionizing radiation and papillary thyroid cancer in women. To further evaluate potential mechanisms in carcinogenesis, the expression of p53, c-erbB-2, as well as Ki-67, estrogen and progesterone receptors were analyzed by immunohistochemistry in 19 women exposed to X-rays and for comparison in nine women without such reported exposure. They all had papillary thyroid cancer. No difference was found between these groups. The results of this study showed that p53, c-erbB-2, Ki-67, estrogen and progesterone receptors are not involved in papillary thyroid cancer associated with exposure to medical diagnostic ionizing radiation.

Adult↗
PubMed1997

Depth for dose calibration in high energy photon beams.

BACKGROUND AND PURPOSE: The normalisation depth for determination of output factors in photon fields has frequently been the depth of dose maximum. At high energies the contribution from contaminating electrons is significant at dose maximum and is critically dependent on the beam geometry parameters, which is why a larger depth should be preferred. MATERIALS AND METHODS: The effect of electron contamination was studied using a purging magnet to remove charged particles from the treatment head and a helium bag to minimise production between the head and the phantom. RESULTS: A depth of 10 cm was found to be beyond the range of the contaminating electrons for photon energies up to 20 MV (TPR(20)(10) = 0.772). However, at 50 MV (TPR(20)(10) = 0.810) contaminating electrons contribute 2-3% to the absorbed dose at 10 cm depth. CONCLUSIONS: 10 cm is recommended as both reference and normalisation depth for all megavoltage photon beam qualities, i.e. 60Co and X-rays from accelerators up to 50 MV.

Calibration↗
PubMed1997

Semi-conductor detectors in output factor measurements.

BACKGROUND AND PURPOSE: Output factors are generally measured with cylindrical ionization chambers. It was investigated if Si-diodes of p-type instead could be used. The advantage would be the small detector size and the robust construction of the detector. MATERIALS AND METHODS: Two types of diodes were studied, one with a shielding layer of tungsten specially made to reduce the excess response for scattered photons and one standard diode without any extra shielding. The measurements were performed at accelerating potentials between 4 and 50 MV and beam sizes between 4 cm x 4 cm and 40 cm x 40 cm. RESULTS: The results showed that both types of diodes are suitable for measurements of head scatter factors in mini-phantoms. However, the diodes were found inappropriate for measurement of output factors for large fields in extended water phantoms. For small fields (<10 cm x 10 cm) a small detector is advantageous and no errors due to the scatter contribution were seen. CONCLUSIONS: An cylindrical ionization chamber is the best choice for output factor measurements in extended water phantoms for large field sizes while diodes are an alternative in small fields. There were negligible differences between the detectors in head scatter measurements in mini phantoms.

Humans↗
PubMed1996

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↗
PubMed1996

Endothelial adhesion molecules for nasal-homing T cells in allergy.

During the allergic reaction mucosal T cells are activated and a local increase in numbers occurs. In peripheral blood, a concomitant T cell activation and switch towards memory phenotype appears. E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were studied in nasal mucosal biopsies taken during a time-course provocation study, including patients with seasonal allergic rhinitis and healthy controls. Allergic patients were also studied during the natural pollen season with particular attention to the influence of local corticosteroid treatment. Before provocation allergic patients and controls did not differ concerning the expression of endothelial adhesion molecules. However, the epithelial ICAM-1 expression was increased among allergics (P < 0.05). Repetitive allergen provocation induces an increased endothelial expression of VCAM-1 in allergic patients (P < 0.01). Similarly, VCAM-1 expression was increased during the natural pollen season (P < 0.05). Interestingly, the increased VCAM-1 expression was inhibited by the use of local corticosteroids. The present data demonstrate a putative integrin-VCAM-1 mechanism for selective homing of T memory cells to the allergic nasal mucosa and new in vivo effects of local corticosteroid treatment are demonstrated.

Adrenal Cortex Hormones↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

p53 and Rb immunostaining in locally advanced bladder cancer: relation to prognostic variables and predictive value for the local response to radical radiotherapy.

The association between known prognostic variables and altered immunostaining for the nuclear proteins retinoblastoma (Rb) and p53 was studied in a homogeneous series of locally advanced bladder cancer. The predictive value of this immunostaining for the local response to intended radical radiotherapy was investigated. Among 262 patients treated with intended radical radiotherapy between 1967 and 1986, a total of 154 patients were evaluable with respect to local response to treatment. The paraffin-embedded specimen from the tumour prior to irradiation was immunostained with the monoclonal antibodies PMG3-245 for Rb and 1801 for p53 nuclear proteins after heating in a microwave oven for 40 min at 650 W. An altered expression of Rb and p53 was observed in 18 and 42% of the tumours, respectively. p53 overexpression was associated with higher tumour grade. However, the results of the p53 and Rb immunostaining procedures had no predictive value for tumor response to radiation treatment, local control or cancer-specific mortality.

Adult↗
PubMed1994

Salivary duct carcinoma--a highly aggressive salivary gland tumour with overexpression of c-erbB-2.

The clinicopathological and immunocytochemical features of nine cases of salivary duct carcinoma are described. This relatively rare tumour, which only recently has been widely recognized as a separate entity, is highly malignant and caused the death in eight of the patients. The tumour cells are arranged in cribriform and solid growth patterns, where the solid tumour nests frequently have comedo necrosis, and a fibrous, often sclerotic, stroma is present. The infiltrating desmoplasmic component and the diffuse invasive growth into adjacent adipose parotid tissue have similarities to ductal breast carcinoma. Immunocytochemical investigation of salivary duct carcinoma showed constant overexpression of c-erbB-2 as detected by membrane accentuation, and high proliferative activity as detected by nuclear positivity for MIB 1 (Ki-67). Changes in the expression of p53 and retinoblastoma gene product do not constitute a constant event in salivary duct carcinoma. A few of the tumours showed scattered cells with distinct nuclear positivity for both progesterone and oestrogen receptors. We emphasize that this highly malignant salivary gland tumour has a characteristic morphology, may not be as rare as previously considered, and that prompt and aggressive therapy is needed.

Adult↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1992

Nasal memory T lymphocytes capable of producing IL-4 in the allergic reaction.

This paper reports the presence of memory T cells in the nasal mucosa of allergic patients. The demonstration of CD4+/CD29+ (CD4+/CD45RO+) T lymphocytes, which are capable of interleukin-4 production, can indicate a complementary cell-mediated regulatory mechanism for mast cell proliferation and IgE synthesis in human nasal allergy. No substantial IgE production can be obtained in the absence of IL-4. Therefore, the existence of IL-4 producing cells on site in the nasal mucosa of allergic subjects probably implies a complementary interaction between cytokines and different immunocompetent nasal cells in the regulation of B cells and IgE synthesis.

Cytokines↗
PubMed1992

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↗
PubMed1990

Perinatal hypoadrenalism in the rat does not alter glucose tolerance and insulin secretory response to glucose.

Fetal and neonatal hypoadrenalism was induced by treating rat mothers with metyrapone from day 12 of pregnancy to day 7 postnatally. Hypoadrenalism in the neonates was indicated by a slight reduction in body weight, adrenal hyperplasia and a tendency towards reduced adrenal corticosterone concentration. An intraperitoneal glucose tolerance test on the 7-day old neonates did not show any disturbancies of glucose disposal or insulin secretory response to glucose. The data suggest that adrenal corticosteroids are not essential for the perinatal development of the B-cell secretory response to glucose.

Adrenal Insufficiency↗
PubMed1987

Mechanisms of congenital malformations in diabetic pregnancy.

The reasons for the increased rate of congenital malformations in diabetic pregnancy are unclear. Several different teratological agents may be considered. In clinical investigations and animal experimentation hyperglycemia and hypoglycemia, hyperketonemia, altered trace metal metabolism, and a genetic predisposition have been suggested to be of significance in the teratogenic process of diabetic pregnancy. Studies of these possible etiological factors have so far failed to reveal a single agent or mechanism as the most important. The diabetic pregnancy, therefore, appears to be of multifactorial origin.

3-Hydroxybutyric Acid↗
PubMedDate not supplied

Phenotype switch and activation of T lymphocytes in patients with allergic rhinitis.

The peripheral blood of 17 patients with seasonal allergic rhinitis (birch pollen) and of 10 healthy subjects were analysed before and during a provocation study in the non-pollen season as well as during the pollen season. Analytical flow cytometry comprised a panel of monoclonal antibodies investigating helper/suppressor T cells, activated T cells, and naive/memory T helper cells. Allergic patients showed no increase in the amount of T lymphocytes but an increased proportion of CD4+ helper T cells early during pronounced exposure (provocation) but not during natural antigen exposure (pollen season). Allergic patients showed a significant increase in activated T cells during the non-pollen season compared with healthy subjects, and furthermore, the nasal allergen provocation induced an additional increase in activated T cells among allergics. The T cell activation mainly affected helper T cells (85%) rather than suppressor T cells. Furthermore, allergic patients showed a significant increase in naive T helper cells during the pollen season. The presence of a double-positive subpopulation indicates an activated T helper subpopulation that switches its phenotype from naive (CD45RA) to memory (CD29). The results indicate at least two important differences between patients with allergic rhinitis and healthy controls. In allergic patients T helper cells become activated upon allergen exposure, and circulate in the blood and switch their phenotype. These T cells have a potential homing tendency to the nasal mucosa. These two events do not occur in non-allergic individuals and may thus constitute new insights into the basic mechanisms of allergic rhinitis.

Adolescent↗