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Biomedical subjects

G Andersson

Publications and source records attributed to G Andersson.

At least 199 records · Page 11Linked to original sources
PubMed1991

Francisella tularensis-induced in vitro gamma interferon, tumor necrosis factor alpha, and interleukin 2 responses appear within 2 weeks of tularemia vaccination in human beings.

Cell-mediated immunity is essential for protection against the intracellular bacterium Francisella tularensis, which causes tularemia. Positive in vitro T-cell responses in the form of lymphocyte proliferation and lymphokine interleukin 2 (IL-2) and gamma interferon (IFN-gamma) secretion are found in memory immunity. Studies on the secretion of lymphokines with regard to the developing immunity to F. tularensis have not been published. Therefore, 14 subjects with no clinical history of tularemia were vaccinated with a live F. tularensis vaccine strain. The in vitro responses of five subjects (antigen-induced mononuclear cell and whole blood culture DNA synthesis and cytokine secretion) were measured twice a week throughout the period from 0 to 35 days after vaccination, and the peripheral blood lymphocyte subpopulations of nine subjects were determined between days 0 and 14. Positive reactions, i.e., responses exceeding those on day 0, were reached on day 10 with regard to the whole blood culture DNA synthesis response and IL-2 and IFN-gamma secretion and on day 14 with regard to the mononuclear cell DNA synthesis response and tumor necrosis factor alpha (TNF-alpha) secretion. No measurable IL-4 was found in either the immune or nonimmune supernatants. Since the secretion of TNF-alpha was related to immunization, this points to the specificity of the phenomenon, even though the type of secreting cell is not yet known. If it is shown later that specific T cells produce it, the TNF-alpha response and the negative IL-4 finding may speak for the importance of the Th1-like pattern in immunity to F. tularensis.

Adult↗
PubMed1991

Acetylcholine receptor-reactive T and B cells in myasthenia gravis and controls.

Myasthenia gravis (MG) is strongly associated with antibodies to acetylcholine receptor (AChR), whereas the extent of T cell involvement is not settled. The number of cells secreting interferon-gamma (IFN-gamma) in response to AChR during 48 h culture of blood mononuclear cells (PBL) may reflect AChR-reactive T cells. Using an immunospot assay, we detected such cells in 23 of 30 patients with MG at a mean number of 1 per 33.333 PBL. AChR-reactive T cells were also found in patients with other neurological diseases (OND) and in healthy subjects but at lower frequencies and numbers. The T cell response to purified protein derivative and to PHA, and also to two major myelin proteins (basic protein and proteolipid protein) did not differ between MG and the two control groups, underlining the specificity of an augmented T cell reactivity to AChR in MG. Evaluation of the B cell response by enumerating anti-AChR IgG antibody secreting cells revealed such cells in 27 of 28 patients with MG at a mean value of 1 per 14,085 PBL. Cells secreting anti-AChR antibodies of the IgA and IgM isotypes were also detected in MG, but less frequently, at lower numbers, and only in conjunction with IgG antibody secreting cells. Anti-AChR antibody secreting cells were also found among patient with OND and in healthy controls, but at lower frequencies and numbers. These data confirm that AChR is a major target for autoimmune response in MG.

B-Lymphocytes↗
PubMed1991

Intestinal immune responses in humans. Oral cholera vaccination induces strong intestinal antibody responses and interferon-gamma production and evokes local immunological memory.

We have examined secretory antibody and cell-mediated immune responses to oral cholera vaccine in the human gastrointestinal mucosa. Freshly isolated peripheral blood lymphocytes and intestinal lymphocytes obtained by enzymatic dispersion of duodenal biopsies were assayed for numbers of total and vaccine specific immunoglobulin-secreting cells by enzyme-linked immunospot assay (ELISPOT) techniques; the frequency of cells secreting interferon-gamma (IFN-gamma) was also examined by a new modification of the ELISPOT technique. After booster immunizations with oral cholera vaccine, large numbers of cholera toxin-specific antibody-secreting cells (ASC) appeared in the small intestine. The responses were dominated by IgA ASC. A single immunization, performed 5 mo after the initial vaccinations, gave rise to an ASC response similar to that seen after the first booster immunization, with respect to both magnitude and isotype distribution. Each of the immunizations also evoked an ASC response in blood which was of lower magnitude than that seen in the small intestine, and comprised similar proportions of IgA and IgG ASC. A booster immunization also resulted in increased frequencies of IFN-gamma-secreting cells, but this increase was confined to the duodenal mucosa. This study establishes the feasibility of studying, at the single-cell level, intestinal immune reactivity in humans. Furthermore, it indicates that the small intestinal mucosa is an enriched source of IFN-gamma. It also demonstrates marked differences between intestinal and peripheral blood immune responses after enteric immunization, and confirms the notion that the mucosal immune system in humans displays immunological memory.

Administration, Oral↗
PubMed1991

Soluble fecal acidic lipids and colorectal epithelial cell proliferation in normal subjects and in patients with colon cancer.

Soluble fecal acidic lipid concentrations and colonic epithelial cell proliferation rates, two biologic markers for colon cancer, were compared in a group of colon cancer patients and a group of healthy controls. No significant difference was found in the concentration of bile acids (155 (136) microM, n = 33, versus 103 (89) microM, n = 19) in the aqueous phase of feces from patients and controls or in proliferation rates between the two groups, the volume density of tritiated thymidine-labeled epithelial cells being 0.153 (0.050), n = 8, for the patients and 0.164 (0.072), n = 11, for the controls. When the dietary intake of three food components known to influence both of the above factors (that is, fat, fiber, and calcium) was ascertained for the year preceding the study, the only significant difference observed was the higher calcium intake in the female patients than in the controls. The authors conclude that it may be premature to rely too heavily on either of the above markers to predict risk for developing this disease.

Adult↗
PubMed1990

NF-X2 that binds to the DRA X2-box is activator protein 1. Expression cloning of c-Jun.

Human class II MHC Ag are a family of cell surface glycoproteins. Their constitutive expression is limited to B lymphocytes and thymic epithelial cells. In many other cells their expression can be induced by IFN-gamma. Conserved upstream promoter sequences regulate this tissue-specific expression of class II genes. In the DRA promoter, one of these cis-acting regulatory motifs is the X2-box to which nuclear factor X2 (NF-X2) binds. Here, we present the isolation and characterization of the full-length cDNA clone encoding NF-X2. This cDNA clone was isolated by expression cDNA cloning, and encodes the human c-Jun protein, which together with c-Fos forms the heterodimeric activator protein-1 transcription complex. Whereas c-Fos/c-Jun heterodimers do not exist in B cells, they form and bind to the X2-box in class II nonexpressing cells. Thus, c-Fos/c-Jun heterodimers might contribute to the repression of DRA gene expression.

B-Lymphocytes↗
PubMed1990

Cellular and humoral immune responses to Plasmodium falciparum gametocyte antigens in malaria-immune individuals. Limited response to the 48/45-kilodalton surface antigen does not appear to be due to MHC restriction.

We have examined immune responses to a cultured Plasmodium falciparum gametocyte lysate and to an affinity-purified preparation of the 48/45-kDa gamete surface Ag in a group of 30 malaria immune individuals and in 24 Europeans with no previous exposure to malaria. Cellular responses were assessed in vitro by lymphoproliferation and production of IFN-gamma; antigamete antibodies were detected by immunofluorescence, Western blotting, and competitive ELISA. Cells from all the malaria immune donors responded to the gametocyte lysate in both assays while cells from nonimmune donors gave only weak proliferative responses. Antigamete antibodies were detected in the serum of all the immune donors but not in serum from nonimmunes. Nonimmune donors were completely unresponsive to the purified 48/45-kDa surface Ag while cells from 40% of immune donors responded by either proliferation or IFN-gamma production. Only 3 of 30 immune donors had detectable antibodies to the 48/45-kDa Ag. Class II HLA type was determined for 27 of the immune donors but no relationship between HLA-DR or -DQ and responsiveness to the 48/45-kDa Ag was discerned. The possible reasons for limited recognition of this gamete surface Ag are discussed.

Animals↗
PubMed1990

Similar induction of the hepatic EGF receptor in vivo by EGF and partial hepatectomy.

A 2-fold increase in the level of epidermal growth factor (EGF) receptor mRNA accompanied by a similar increase in newly synthesized ligand-binding EGF-receptors was observed 2-4 h after intraportal EGF-injections and 2-4 h after partial hepatectomy. After this initial increase, the EGF-receptor levels decreased back to control levels 6-8 h after EGF-injections and below control levels 6-8 h after partial hepatectomy. EGF was also found to influence the degradation of endocytosed [125I]-EGF 3 h after injection to a similar extent as partial hepatectomy. The similar effects of EGF and partial hepatectomy suggests that EGF or EGF-like factors may be mechanistically involved in the early "promotion" stage during the pre-replicative phase of liver regeneration. The EGF-induced effects are, however, at least not alone responsible for the replicative process.

Animals↗
PubMed1990

Detection of intracellular expression and secretion of interferon-gamma at the single-cell level after activation of human T cells with tetanus toxoid in vitro.

Activation of T cells results in intracellular expression and secretion of cytokines such as interferon (IFN)-gamma. Here we have used three different assays for determination of IFN-gamma in tetanus toxoid- or mitogen-activated human T cell cultures. Two of these assays [intracytoplasmic immunofluorescence and enzyme-linked immuno spot assay (ELISPOT)] determined the expression and secretion of IFN-gamma at the single-cell level while the third assay enzyme-linked immunosorbent assay (ELISA) measured IFN-gamma secreted into the culture supernatant. Comparison of all three tests revealed a good correlation between the ELISPOT assay and the ELISA, whereas expression of intracellular IFN-gamma showed a qualitative but not a quantitative correlation with the latter. Both the immunospot assay and the immunofluorescence may be used to detect approximate numbers of specific T cells even when present at low frequencies. With the use of the immunospot assay antigen-specific T cells could be detected even in the absence of detectable IFN-gamma in the culture supernatants. However, the ELISA assay should be more convenient for screening large clinical material.

Antigens↗
PubMed1990

Pretranslational and posttranslational regulation of the EGF receptor during the prereplicative phase of liver regeneration.

We studied the regulation of the epidermal growth factor receptor mRNA and the number of epidermal growth factor binding sites in subcellular compartments involved in the biosynthesis and endocytosis of the epidermal growth factor receptor during the prereplicative phase of liver regeneration. The epidermal growth factor receptor mRNA, quantified by solution hybridization, decreased after partial hepatectomy, with a nadir of about 35% 18 hr after hepatectomy. An even stronger decrease in the number of epidermal growth factor binding sites after partial hepatectomy was observed in a Golgi-enriched low-density membrane fraction, reflecting available newly synthesized epidermal growth factor receptors. It is suggested that this decrease in newly synthesized available epidermal growth factor receptors is caused primarily, but not entirely, by decreased epidermal growth factor receptor mRNA levels and the additional down-regulation of epidermal growth factor binding sites may involve posttranslational mechanisms such as intracellular occupation by transforming growth factor-alpha. The observation that the number of specific epidermal growth factor binding sites after partial hepatectomy was only moderately reduced in prelysosomal endosomes and in lysosomes, compared with the newly synthesized receptors, may indicate that a pool of receptors targeted for lysosomes exists and these receptors are regulated in a different manner than the receptor pool targeted for the cell surface. Furthermore, at least two separable endocytic subcompartments are involved in the transport of the epidermal growth factor/epidermal growth factor receptor complex in the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Ultrastructural localization of a tartrate-resistant acid ATPase in bone.

Osteoclasts are effector cells in bone breakdown, and the active bone resorption is confined to the ruffled border zone of these cells. An acid milieu is maintained in this zone which is probably a prerequisite for bone resorption. Tartrate-resistant acid phosphatase (TRAP) activity has been recognized as a characteristic property of osteoclasts and in several studies proposed as a cytochemical marker of osteoclasts. We have previously isolated and characterized a tartrate-resistant and iron-activated acid ATPase (TrATPase) from rat bone, the enzyme being a member of the TRAP family. In the present study the ultrastructural localization of this enzyme was delineated by employing immunogold technique on low temperature-embedded maxillar rat bone. Intensive immunolabeling was seen on the bone surfaces facing the ruffled border zone while lower amounts of marker were seen in adjacent bone areas, that is, on the bone surfaces facing the clear zone and deeper-into the bone. Within the osteoclasts gold markers were observed mainly in vesicular structures interpreted as lysosomes. Immunolabeling was also observed in the recently described endocytic cells located near osteoblasts and osteoclasts. Also in these cells, the marker was confined to lysosomelike structures. The amount of label in bone facing osteoblasts was low, as was the amount within osteoblasts. Our observation of extracellular localization, in particular accumulation of TrATPase in bone matrix facing the ruffled border area of the osteoclasts, favors the view that the enzyme is exported to areas of active bone resorption, thereby indicating a potential role for the enzyme in this process.

Adenosine Triphosphatases↗
PubMed1990

Decreased expression of the growth hormone receptor and growth hormone binding protein in rat liver nodules.

The growth hormone receptor (GHR) and growth hormone-binding protein (GH-BP) expression were characterized in liver nodules and hepatomas from male Wistar rats. The mRNA levels of GHR and GH-BP, studied by northern blot analysis and solution hybridization, were 35-50% (in nodules) and 2-6% (in hepatomas) of the level found in liver from untreated, age-matched rats. The binding of 125I-labeled human growth hormone to a low-density membrane fraction (LDMF) containing Golgi and endosome membranes in the presence of excess ovine prolactin was 75-80% lower in nodules than in liver. When endogenous ligand was removed, the binding increased in nodules but not in liver. Affinity cross-linking experiments revealed identical specific receptor-binding protein complexes at Mr of 95,000, 55,000, and 43,000 in both nodules and liver, assuming stochiometric binding of ligand. The in vivo endocytosis of 125I-labeled bovine growth hormone correlated with the level of GH binding and was thus reduced 75-80% in nodules, compared with liver. The level of insulin-like growth factor-I (IGF-I) mRNA was reduced by 50% in nodules; however, GH administration resulted in a twofold induction of IGF-I mRNA in both nodules and liver. It is concluded that the greater proportion of occupied GHR in nodules could result from an impaired dissociation of endogenous GH, which might explain the reduced GHR mRNA expression. Furthermore the low GHR mRNA expression may reflect a de-differentiated phenotype in nodules.

Animals↗
PubMed1990

Histochemistry and biochemistry of tartrate-resistant acid phosphatase (TRAP) and tartrate-resistant acid adenosine triphosphatase (TrATPase) in bone, bone marrow and spleen: implications for osteoclast ontogeny.

In order to evaluate the usefulness of a recently described acid ATPase as a marker for osteoclast differentiation, we have performed histochemical and biochemical analyses of the distribution of tartrate-resistant acid phosphatase (TRAP) and tartrate-resistant acid ATPase (TrATPase) in bone, bone marrow and spleen. Histochemical studies of bone demonstrated that multinucleated osteoclasts stained for both TRAP and TrATPase. However, staining for TRAP covered the entire cytoplasm, whereas TrATPase staining was localized primarily to cytoplasmic areas next to bone and on adjacent mineralized surfaces. Occasionally TrATPase-positive mononuclear cells were observed on excavations in the bone surface. In the spleen, mononuclear TRAP-positive cells were located in the marginal zone between the white and red pulp, whereas no staining for TrATPase was observed. Comparison of the biochemically measured TRAP and TrATPase activities showed that bone had the highest specific activity for both enzymes followed by the bone marrow and spleen. However, enzyme activity in the spleen compared to bone was about 4-fold higher for TRAP compared to TrATPase. Additional evidence for a restricted expression of TrATPase to bone relative to spleen was obtained by in vitro translation studies. These data indicate that TrATPase is a more selective marker than TRAP in histochemical and biochemical studies of osteoclast differentiation and furthermore suggest that development of TrATPase is a late acquisition in osteoclast ontogeny.

Acid Phosphatase↗
PubMed1990

Helicobacter pylori induces lymphocyte activation in peripheral blood cultures.

Helicobacter pylori-induced in vitro stimulation of mononuclear cells was characterized by measuring DNA synthesis response, interferon-gamma (IFN-gamma) secretion and the number of immunoglobulin-secreting cells. The strength of these responses was measured in 51 subjects comprising 36 dyspeptic patients from the Gastroenterological Unit and 15 members of the laboratory staff. Nineteen subjects had antibodies to H. pylori and 32 did not. The responses were compared with respect to H. pylori antibody status. Positive stimulation of DNA synthesis (stimulation index greater than 2) was obtained in 96% of the subjects, and the bacterium induced IFN-gamma secretion in all of them. The induction of immunoglobulin-secreting cells revealed B cell in vitro stimulation. The antibody-positive subjects had a tendency to synthesize less DNA (P not significant) and secrete less IFN-gamma (P less than 0.05) in response to H. pylori than did the antibody-negative ones, but the differences were not marked. The results show that the whole H. pylori bacterium stimulates mononuclear cells. The nature of the stimulation is not yet characterized (non-specific versus specific).

Antibodies, Bacterial↗
PubMed1990

Impact of consumption factors on soft tissue changes in Swedish moist snuff users: a histologic study.

The purpose of this study was to analyze the relative importance for histologic changes of the oral mucosa of such consumption factors as years with regular snuff use, hours and grams of daily snuff use. The material consisted of biopsies of selected cases (two groups) from 252 regular snuff users of whom 184 used exclusively loose and 68 exclusively portion-bag packed snuff. Group 1 comprised 8 pairs of loose snuff users with large differences (14-45 yr) in terms of years with regular habit. Many years of snuff use did not per se seem to result in tissue changes which significantly differed from changes seen in subjects with only a few years of loose snuff use. Group 2 included 5-10 subjects showing the lowest and highest daily consumption of loose or portion-bag packed snuff. Among those with a low daily consumption, portion-bags seem to be related to less pronounced changes than loose snuff. High daily snuff use was associated with relatively somewhat more pronounced epithelial surface changes but histologic differences between the two habit groups were difficult to identify.

Adolescent↗
PubMed1990

Regulation of epidermal growth factor receptor metabolism in gingival fibroblasts by phenytoin in vitro.

Normal human gingival fibroblasts derived from five children between 8 and 12 yr of age were cultured under serum-free conditions in the presence of epidermal growth factor (EGF) either alone or in combination with 5,5-diphenylhydantoin (phenytoin; PHT). DNA-synthesis, binding of EGF to its cell-surface receptor and internalisation of EGF-receptor-ligand complexes were studied. In normal gingival fibroblasts treated solely with EGF for 48 h, DNA synthesis increased significantly, as in cells treated solely with PHT. When EGF binding data was calculated according to Scatchard, it was found that the number of EGF receptors in fibroblasts increased significantly after PHT treatment. The number of EGF-receptors in untreated gingival fibroblasts varied from 147,000 to 170,000 receptors per cell whereas in PHT-treated fibroblasts the range was from 181,000 to 280,000. The study indicates that PHT regulates EGF-receptor metabolism in human gingival fibroblasts by increasing the number of cell-surface EGF-receptors which may contribute to the alteration of gingival connective tissue observed in patients undergoing PHT medication.

Child↗