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Biomedical subjects

G Hetland

Publications and source records attributed to G Hetland.

At least 19 recordsLinked to original sources
PubMed2006

Effects on gene expression and viral load of a medicinal extract from Agaricus blazei in patients with chronic hepatitis C infection.

Extracts from the mushroom Agaricus blazei Murill (AbM) are used extensively as a non-prescription remedy against cancer and infections, including hepatitis. We previously demonstrated a potent immunomodulating effect of a particular preparation on monocytes in vitro, and a protective effect on bacterial infections in mice. Here we report the effect on gene expression in peripheral blood cells from four chronic hepatitis C patients, using global (29 k) oligo-based, single channel microarrays. The viral load was slightly, but not significantly, decreased after 1 week of AbM treatment. The cytokine genes most strongly induced in vitro were not induced in vivo. The more notable changes in mRNA levels were related to genes involved in the G-protein coupled receptor signalling pathway, in cell cycling, and in transcriptional regulation. The results suggest that the beta-glucans of the extract, which presumably are responsible for cytokine induction, did not readily enter the blood, while other components, such as substances proposed to have anticancer effects, were active in the blood.

Administration, Oral↗
PubMed2005

Allergic sensitisation in tuberculosis and leprosy patients.

BACKGROUND: A negative association has been observed between infections and allergy in several studies. The aim of the present study was to examine whether tuberculosis and leprosy patients have more or fewer allergies than healthy individuals. METHOD: Sera from tuberculosis patients, leprosy patients and healthy controls were analysed by ELISA and Pharmacia Unicap for serological markers for allergy and mycobacterial infection. The serological markers for allergy were total IgE, specific IgE using Phadiatop and specific IgE to the dust mite allergen Dermatophagoides pteronyssinus 1 (Der p 1). Serological markers for mycobacterial infections included specific IgG to a mixture of bacille Calmette-Guérin culture filtrate antigens, to purified mannose-capped lipoarabinomannan (manLAM) and to purified secreted antigen 85B. RESULTS: Both tuberculosis and leprosy patients had significantly higher levels of total IgE than controls. Furthermore, a significantly higher level of specific IgE (Phadiatop) was also found in the tuberculosis patients compared with controls. A similar result, but not statistically significant, was observed for the leprosy group. Specific IgG to antigen 85B and to manLAM was found to be significantly higher in both tuberculosis and leprosy patients compared with controls. In addition, leprosy patients had significantly more IgG to the BCG culture filtrate antigen than controls. CONCLUSIONS: The results indicate that patients with mycobacterial infections have allergic sensitisation more frequently compared with healthy controls. This is seemingly in contrast with the notion that there is a negative association between allergy and infection ('hygiene hypothesis'). However, since only one in ten of those infected with Mycobacterium tuberculosis will develop the disease, patients with active mycobacterial disease represent a selected group. A similar relationship applies for leprosy. It is conceivable that those predisposed to allergy are less resistant to mycobacterial infections.

Adult↗
PubMed2005

Effect of a medicinal extract from Agaricus blazei Murill on gene expression in a human monocyte cell line as examined by microarrays and immuno assays.

Extracts from the edible mushroom Agaricus blazei Murill (AbM) are used extensively as a non-prescription remedy against cancer, infections, and immune related diseases. The presumed effect is to activate certain parts of the immune system. In order to investigate the effect, we examined the changes of gene expression caused by the extract on a human monocyte cell line (THP-1). Changes in the levels of mRNA transcripts were measured using 35 k microarrays, and the changes in select cytokine gene products by immuno assays. Lipopolysaccharide (LPS) was included for comparison. Both AbM and LPS had drastic effects on gene expression. Genes related to immune function were selectively up-regulated, particularly proinflammatoric genes such as the interleukins IL1B and IL8. Although most genes induced by AbM were also induced by LPS, AbM produced a unique profile, e.g., as to a particular increase in mRNA for the cytokines IL1A, CXCL1, CXCL2 and CXCL3, as well as PTGS2 (cyclooxygenase2).

Agaricus↗
PubMed2005

An extract of the mushroom Agaricus blazei Murill administered orally protects against systemic Streptococcus pneumoniae infection in mice.

The aim was to investigate the antibacterial effect of the biologically active and edible mushroom Agaricus blazei Murill (AbM). A water extract of AbM or PBS control was administered orally before or with challenge to NIH/OlaHsd mice, experimentally infected intraperitoneally with the moderately virulent Streptococcus pneumoniae serotype 6B. End points were bacteraemia and survival rate. The AbM extract, protected against systemic S. pneumoniae 6B infection in the mice. It was most effective when given 24 h before inoculation but did also have protective effects when given together with challenge compared with control. The lack of antibiotic effect on pneumococci in vitro and increased levels of cytokines MIP-2 and TNF-alpha in the serum of mice receiving AbM extract, indicated that the protective effect of AbM was due to the involvement of the native immune system. This is the first report of anti-infection effects of AbM in vivo. Our results suggest that AbM extract may be useful as additional prophylactic and possibly therapeutic treatment against bacterial and possibly other infections in humans.

Adjuvants, Immunologic↗
PubMed2005

Immunoglobulin G antibodies against environmental moulds in a Norwegian healthy population shows a bimodal distribution for Aspergillus versicolor.

Immunoglobulin G (IgG) antibodies against moulds related to indoor dampness problems are used as biomarkers to indicate exposure. In the present study, we evaluated the frequency of mould exposure in an adult healthy population by examining levels of mould-specific IgG antibodies in Norwegian blood donors. Using enzyme-linked immunosorbent assay, 106 blood donor sera were analyzed for IgG antibodies to Aspergillus versicolor, Penicillium chrysogenum, Cladosporium herbarum, Stachybotrys chartarum and Fusarium oxysporum. The levels of specific IgG antibodies to P. chrysogenum, C. herbarum and S. chartarum correlated (r = 0.46-0.62). Responses to A. versicolor were considerably stronger than to the other moulds, and another 996 blood donor sera were analyzed for IgG antibodies to this mould. Women had significantly higher levels of specific IgG antibodies to A. versicolor than men. The concentration of A. versicolor-specific IgG antibodies showed a non-Gaussian, bimodal distribution profile, in which 12.5% were defined as positive to exposure. This suggests that significant mould exposure in a healthy population can be calculated from mean + 1SD. Western blotting analyses showed that antibody responses to A. versicolor were largely directed against carbohydrate antigens of unknown saccharides.

Antibodies↗
PubMed2005

Allergens and endotoxin in settled dust from day-care centers and schools in Oslo, Norway.

UNLABELLED: Allergy to indoor allergens can cause frequent and severe health problems in children. Because little is known about the content of allergens in the indoor environments in Norway, we wanted to assess the levels of cat, dog and mite allergens in schools and day-care centers in Oslo. Allergen levels in dust samples from 155 classrooms and 81 day-care units were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Additionally, we measured the levels of endotoxin in 31 day-care units, using the limulus amebocyte lysate test. Most of the dust samples contained detectable amounts of cat and dog allergens. In mattress and floor dust (day-care centers), and curtain and floor dust (schools) the median Fel d 1 levels were 0.17, 0.002, 0.02 and 0.079 microg/m2, while the median Can f 1 levels were 1.7, 0.03, 0.1 and 0.69 microg/m2, respectively. Levels of cat and dog allergens in school floor dust were associated with the number of pupils with animals at home. In contrast, <1% of the samples had measurable levels of the mite allergen Der p 1. Moreover, the levels of endotoxin tended to be higher in dust from floors (1.4 ng/m2) compared with that from mattresses (0.9 ng/m2). PRACTICAL IMPLICATIONS: To reduce allergen exposure, allergic individuals should be placed in the classes/rooms with the fewest pet owners. Moreover, mattresses in day-care centers are major reservoirs of cat and dog allergens and should be cleaned frequently.

Air Pollution, Indoor↗
PubMed2004

Mould extracts increase the allergic response to ovalbumin in mice.

BACKGROUND: Exposure to moulds in indoor air is thought to induce asthma in susceptible persons. Moulds may contain several potent allergens. However, more importantly, moulds may increase the allergic response to other allergens (adjuvant effect). Previously, we have found that a beta-1,3-glucan from the cell wall of the fungus Sclerotinia sclerotiorum increases the allergic response to the model allergen ovalbumin (OVA) in a mouse model. OBJECTIVE: In the present study, we wanted to confirm the adjuvant effect of another beta-1,3-glucan, MacroGard (MG) from baker's yeast in this model. More importantly, we wished to explore the putative effects of extracts from the moulds Cladosporium herbarum (CH) and Penicillium chrysogenum (PC) using the very same model as used to explore effects of beta-glucans. METHODS: Groups of eight Balb/c mice were injected with OVA alone, OVA+extract or OVA+MG, into one footpad. On day 21, all mice were reinjected with OVA, before exsanguination on day 26. The levels of OVA-specific IgE, IgG1 and IgG2a in serum were measured by ELISA. RESULTS: Compared with OVA alone, OVA+MG, OVA+CH extract and OVA+PC extract increased OVA-specific IgE and IgG1 levels significantly. For all groups, the levels of IgG2a anti-OVA remained similar to those of the OVA-alone group. CONCLUSIONS: Our results show that extracts from CH and PC, and the beta-1,3/1,6-glucan from baker's yeast have adjuvant effects on the allergic response in mice.

Adjuvants, Immunologic↗
PubMed2001

Leptin does not influence the IgE response to ovalbumin in mice.

Leptin is important for maintenance of the body's energy homeostasis and it also increases Th1 and suppresses Th2 cytokine production. We have investigated the effect of leptin on the allergic immune response to the model allergen ovalbumin (OA) by using the popliteal lymph node assay (PLNA) and serum antibody determination in mice. Mice were injected with either leptin i.v. plus OA in one hind footpad, or leptin or OA alone. A booster dose of leptin was given twice and of OA once and the animals were exsanguinated on experimental day 19 when the PLNs also were removed. End-point measurements were serum levels of IgE, IgG1, and IgG2a anti-OA and weight and cell number of the excised PLNs. Leptin given i.v. with the protocol employed altered neither the cellular PLN response nor the specific serum IgE, IgG1, or IgG2a anti-OA levels compared with the group given OA without leptin. Our data indicate that systemic administration of leptin neither suppresses nor enhances the Th2-dependent antibody responses in the present mouse model.

Allergens↗
PubMed2001

Effects of C5a and FMLP on interleukin-8 production and proliferation of human umbilical vein endothelial cells.

Interleukin-8 (IL-8), C5a and N-formyl-methionyl-leucyl-phenylalanine (fMLP) are chemotactic peptides with predominant effects on leukocytes during inflammation. With emphasis on C5a we studied the regulation of the production of IL-8 by human umbilical vein endothelial cells (HUVEC) in vitro. Primary HUVEC cultures were incubated with IL-1alpha, TNFalpha, C5a and fMLP for 24 h and 48 h prior to measurement of IL-8 in supernatants of the cells by an enzyme immunoassay. Whereas IL-1alpha and TNFalpha significantly increased the levels of IL-8, C5a decreased the IL-8 production after 48 h. In addition, the ability of IL-1alpha, TNFalpha, C5a, fMLP and IL-8 to induce cell proliferation was compared by means of a 3H-thymidine incorporation assay. In contrast with IL-1alpha and TNFalpha, both C5a and fMLP increased cell proliferation of HUVEC. This increase occurred with increasing concentrations of C5a contrary to IL-8, which showed increased cell proliferation at low, but not high IL-8 concentrations.

Cell Division↗
PubMed2001

Detection of mRNA for the terminal complement components C5, C6, C8 and C9 in human umbilical vein endothelial cells in vitro.

Human umbilical vein endothelial cells (HUVEC) have previously been shown to synthesize the functional terminal pathway of complement based on the detection by radioimmunoassay of the terminal complement complex (TCC) on coincubated agarose beads. In addition, C7 secretion by these cells in amounts comparable to C3, as well as C7 mRNA, has recently been demonstrated. However, it has not been possible to detect C5-6 and C8 in the fluid phase, and only trace amounts of soluble C9. Against this background we examined whether mRNA for the remaining terminal complement factors was present in HUVEC. By the use of reverse transcription (RT)-polymerase chain reaction (PCR) and Northern blot the presence of mRNA for complement factors C5, C6, C8 and C9 was demonstrated.

Base Sequence↗
PubMed2000

The fungal cell wall component beta-1,3-glucan has an adjuvant effect on the allergic response to ovalbumin in mice.

The polyglucose beta-1,3-D-glucan is a major structural component of the cell wall of yeasts and fungi. In the present study, the adjuvant activity of beta-1,3-glucan from the fungus Sclerotinia sclerotiorum (SSG) on the response to the model allergen ovalbumin (OA) was studied, using the popliteal lymph node assay (PLNA) in BALB/c mice. The adjuvant activity on the local cellular response was determined by measuring the weight, cell number, and proliferation of the extracted PLNs. The levels of OA-specific immunoglobulin (Ig)E, IgG1, and IgG2a in serum were measured by enzyme-linked immunosorbent assay (ELISA). Groups of 8 mice were given either SSG + OA, SSG alone, or OA alone on d 0. Thereafter they were exsanguinated on d 20, or reinjected with OA on d 21, before exsanguination on d 26 or 33. Only on d 26 was SSG + OA found to significantly increase the PLN weight and cell numbers, but not cell proliferation (thymidine incorporation), compared with OA or SSG alone. SSG + OA was also found to significantly increase both the anti-OA IgE and IgG1 levels on d 20, 26, and 33 compared to OA alone. Compared to SSG alone, SSG + OA increased the OA-specific IgE and IgG 1 levels significantly on d 26 and 33, but not on d 20. A similar increase was not found for IgG2a. Our results show that beta-1,3-D-glucan provides a clear Th2-dependent (allergic) immune response to OA, indicated by elevated levels of IgE and IgG1 and not IgG2a, in the mouse model used.

Adjuvants, Immunologic↗
PubMed2000

Protective effect of Plantago major L. Pectin polysaccharide against systemic Streptococcus pneumoniae infection in mice.

The antibacterial effect of a soluble pectin polysaccharide, PMII, isolated from the leaves of Plantago major, was examined in inbred NIH/OlaHsd and Fox Chase SCID mice experimentally infected with Streptococcus pneumoniae serotype 6B. Serotype 6B is known to give a more protracted infection when injected intraperitoneally into susceptible mice than more virulent serotypes like type 4. PMII was administered i.p. either once 3 days before challenge or once to thrice from 3 to 48 h after challenge. The number of bacteria in blood and the mouse survival rate were recorded. Pre-challenge administration of PMII and also lipopolysaccharide (LPS), included as a control, gave a dose-dependent protective effect against S. pneumoniae type 6B infection. However, injection of PMII after establishment of the infection in NIH/OlaHsd mice had no effect. The data demonstrate that, firstly, the polysaccharide fraction PMII from P. major protects against pneumococcal infection in mice when administered systemically prechallenge, and secondly that the protective effect is owing to stimulation of the innate and not the adaptive immune system.

Animals↗
PubMed2000

Concentrations of leucocyte-associated chemotaxin C5a correlate with the mobilisation of polymorphonuclear leucocytes during operations for rectal cancer.

OBJECTIVE: To describe the profile of potential chemotaxins C5a, interleukin 8 and tumour-necrosis factor alpha, and the peripheral blood leucocyte (PBL) response in five patients having uncomplicated operations for rectal cancer. DESIGN: Prospective study. SETTING: University hospital, Norway. SUBJECTS: Five patients, four men and one woman, median age 66 years (range 48-77) who were operated on for rectal cancer. INTERVENTION: Four had low anterior resections and total mesorectal excision (TME) and one patient had a diverting end sigmoidostomy because of local perirectal spread of the cancer and liver metastases. Blood samples were taken at the start of the operation; peroperatively after 1, 2, and 3 hours; postoperatively at 5, 8, and 24 hours, for analysis of potential chemotaxins. RESULTS: The number of PBL tripled between the start and end of the operation and declined to a slightly lower plateau between 5 and 24 hours. Peroperatively, the association of C5a with PBL increased six-fold resulting in a doubled concentration of C5a/PBL, whereas the corresponding concentration of C5a in plasma remained relatively constant. Postoperatively, the concentration of C5a associated with the PBL and in plasma fluctuated with the maximums being at 8 and 24 hours, respectively. In contrast to C5a in plasma, the concentration of cell-associated C5a correlated with number of PBL or polymorphonuclear leucocytes (PMN). The plasma concentration of IL-8 doubled during the operation, reached a six-fold maximum at 5 hours, and declined after 24 hours to twice the initial concentration. There were no correlations between plasma IL-8 and either number of PBL, plasma C5a, or PBL-associated C5a. No TNF alpha was detected in the plasma. CONCLUSION: Tissue trauma caused by uncomplicated excision of rectal cancer leads to leucocyte mobilisation peroperatively, probably partly by complement activation and subsequent generation and binding of the chemotaxin C5a to PBL. However, other chemotaxins may also play a role.

Aged↗
PubMed2000

Protective effect of beta-glucan against systemic Streptococcus pneumoniae infection in mice.

The antimicrobial effect of soluble beta-1,3-D-glucan from Sclerotinia sclerotiorum (SSG) was examined in mice experimentally infected intraperitoneally (i.p.) with Streptococcus pneumoniae serotypes 4 and 6B. SSG was administered i.p. either 3 days before challenge or 3-48 h after challenge. The number of bacteria in blood samples and the mouse survival rates were recorded. Pre-challenge SSG administration protected dose-dependently against both S. pneumoniae type 4 and 6B infections. SSG injected 24 h post-challenge had a curative effect against type 6B but not type 4 pneumococcal infection. The data demonstrate that SSG administered systemically protects against pneumococcal infection in mice.

Animals↗
PubMed2000

Mechanism for uptake of silica particles by monocytic U937 cells.

We examined the mechanism for uptake by monocytic cells of particles found in the atmosphere of some industrial work places. As a model system, irregular crystalline silica particles (SPs), sphere-like cryptocrystalline microsilica particles (MPs) and carbon particles (CPs) were exposed to pro-monocytic U937 cells. Plasma-treated SP and MP, but not CP, activated the alternative complement pathway, but bound little C3b. However, all particles adsorbed serum IgG, IgA and IgM unspecifically. Phenotyping of U937 cells for complement receptors (CRs) and Fcgamma receptors (FcgammaRs) showed that interferon gamma (INFgamma) increased expression of FcgammaRI, CR3 (CD11b/CD18) and CR4 (CD11c/CD18) and that phorbol-12-myristate-13-acetate (PMA) increased expression of CR4. Scanning electron microscopy (SEM) demonstrated higher phagocytosis of plasma-treated SP than native SP by both PMA- and INFgamma-stimulated, but not unstimulated, cells. MP and CP could not be distinguished from cellular structures. Inhibition experiments in SEM revealed uptake of heparin-plasma-treated SP via FcgammaRI on INFgamma-stimulated U937 cells, but could not exclude possible participation of CR3. The results indicate that plasma-treated SPs bind Ig and are internalized by differentiated monocytic cells via FcgammaRI, which is known to trigger cellular production of toxic oxygen species that may induce pulmonary inflammation in vivo.

Complement Activation↗
PubMed1998

Processing of C5a by human polymorphonuclear leukocytes.

Uptake of human C5a by neutrophils was monitored in vitro using both 125I-labeled and unlabeled C5a. The ligand was internalized by the cells in a dose-dependent manner and maximal binding/uptake was observed after 5 min of incubation. Neutrophils were incubated with labeled C5a and the cytosol and supernatant were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. C5a degradation products were primarily observed in the supernatant, whereas most of the protein remained intact in the cytosol even after 60 min of incubation. Cytosol from neutrophils incubated for 20 min with unlabeled C5a was examined by radioimmunoassay and found to contain antigenically intact C5a and retained the ability to induce a neutrophil (shape change) response. The functional activity of C5a recovered from the cytosol was inhibited by antibodies to either C5a or the C5a receptor (CD88). This data supports our hypothesis that although C5a is internalized it remains antigenically intact and functionally active inside the cell and is primarily degraded extracellularly.

Complement C5a↗