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Biomedical subjects

S C Mogensen

Publications and source records attributed to S C Mogensen.

At least 37 records · Page 2Linked to original sources
PubMed1991

Bioactive and inactive forms of tumor necrosis factor-alpha in spinal fluid from patients with meningitis.

Twenty-four patients, including 12 with meningitis, were admitted with meningeal symptoms and fever. Their serum and spinal fluid tumor necrosis factor-alpha (TNF alpha) levels were determined by ELISA. TNF alpha immunoreactivity was found in spinal fluid of 10 meningitis patients and one nonmeningitis patient, whereas 7 sera, 5 from meningitis patients, contained TNF alpha. Levels were significantly higher in spinal fluids than in serum samples, and the TNF alpha bioactivity of spinal fluids and sera was considerably below predictions based on ELISA measurements. Gel filtration chromatography demonstrated the presence of both polymeric (greater than 200 kDa) and oligomeric (10-40 kDa) TNF alpha in spinal fluid. Significant bioactivity was obtained only from samples containing oligomeric cytokine. In agreement with previous in vitro findings, these results strongly indicate that bioactive TNF alpha oligomers form inactive polymers and monomers, which could contribute to the observed in vivo discrepancies between immunoreactive and bioactive protein. Finally, the data support the concept of local central nervous system production of TNF alpha in meningitis.

Adolescent↗
PubMed1990

Herpes simplex virus and intraoral ulcers in immunocompromised patients with haematologic malignancies.

Possible factors predisposing to the development of intraoral ulcers in immunocompromised patients with haematologic malignancies were investigated. Among 46 patients undergoing antineoplastic treatment, 18 developed an intraoral ulcer during the prospective study. Patients with or without ulcers were comparable with respect to underlying disease, presence of teeth, the qualitative composition of the aerobic and facultatively anaerobic oral microflora, herpes simplex virus (HSV) titer positivity, a past history of herpes labialis, leukocyte and thrombocyte counts, and duration of fever. Viral cultures from saliva revealed an association between the presence of HSV in saliva and the presence of intraoral ulcers. HSV was not isolated from the saliva of any patient without ulcers. Viral cultures from the ulcers revealed growth of HSV in 11 (61%) of the 18 patients with ulcers. HSV-positive ulcers were located more often on the alveolar process than elsewhere in the oral cavity. Ulcers on the lateral borders of the tongue and on the buccal mucosa were found only in dentate patients. Development of intraoral ulcers was not associated with an increase of the HSV titer in serum in any patient. It is concluded that some intraoral ulcers, especially when located on the alveolar process, are associated with and probably caused by HSV, while mechanical trauma during mastication seems likely to be involved in the pathogenesis of ulcers elsewhere in the oral cavity.

Adult↗
PubMed1989

Bioactive human recombinant tumor necrosis factor-alpha: an unstable dimer?

As determined by native polyacrylamide gel electrophoresis (PAGE) and gel chromatography the molecular mass of native tumor necrosis factor (TNF)-alpha was approximately 35 kDa. When incubated at low concentrations (less than 1 nM) 125I-labeled TNF-alpha and unlabeled TNF-alpha rapidly multimerized or dissociated into monomers and bioactivity decreased. Sodium dodecyl sulfate (SDS)-PAGE analysis of cross-linked 125I-labeled TNF-alpha demonstrated bands of multi- and trimeric TNF-alpha in addition to dominating bands of dimers and monomers. Tri-, di- and monomeric TNF-alpha were recovered from SDS-PAGE gels and allowed to renature. Of the original receptor-binding activity, 10%-15% was obtained with cross-linked TNF-alpha dimers, whereas none was recovered from preparations of trimeric TNF-alpha. Multimeric and monomeric TNF-alpha exhibited little or no binding activity, and cell-bound, cross-linked TNF-alpha which was dissociated from cellular binding sites was mainly dimeric. 125I-labeled TNF-alpha bound to lymphokine-activated killer (LAK) cells and binding kinetics were much similar (Kd approximately 100 pM) to those reported in other normal cell types. The number of receptors per LAK cell was approximately 4 x 10(3). Cross-linking of TNF-alpha to binding sites in U-937 and LAK cells yielded a receptor-ligand complex of about 80/90 kDa. At 37 degrees C, 125I-labeled TNF-alpha was rapidly internalized and degraded in L-929, U-937 and LAK cells. Degradation of ligand and recycling of receptors were blocked in the presence of methylamine. Methylamine significantly inhibited TNF-alpha-mediated cytolysis of L-929 cells and caused a quantitatively corresponding reduction in cellular TNF-alpha uptake, indicating that L-929 lysis was mediated by receptors.

Cell Survival↗
PubMed1989

Effects of selenium on toxicity and ultrastructural localization of mercury in cultured murine macrophages.

The effects of selenium on cellular toxicity and histochemical distribution of mercury were examined in a cell culture system of mouse peritoneal macrophages. Selenium protected against the toxicity of mercury in cultures exposed to 4 microM of mercuric chloride. Selenomethionine caused a significant increase in cell survival throughout the experiments, while sodium selenite delayed the toxicity of mercury for a while, after which selenite itself had a toxic effect. The amount of mercury visualized by autometallography was increased in macrophage cultures pre-exposed to sodium selenite or selenomethionine. The additional mercury made visible by this histochemical demonstration was located in the cytoplasm as well as in the lysosomes.

Animals↗
PubMed1989

Herpes simplex virus type 2 primes mouse macrophages for an early and genetically determined respiratory burst mediated by interferon-alpha/beta.

The influence of infection by herpes simplex virus type 2 (HSV-2) on the respiratory burst capacity of mouse macrophages was studied by luminol-dependent chemiluminescence with phorbol myristate acetate (PMA) as trigger. Peritoneal cells from virus-infected mice were strongly primed for a respiratory burst during the acute phase of the infection. By 12 h after infection the response had increased 40-fold over control values. Most of the response was elicited by mononuclear phagocytes. When resting peritoneal macrophages were infected with HSV-2 in vitro a maximal priming effect was seen with 2 x 10(6) p.f.u./ml of virus after 8 h, but a significant response was obtained after 4 h of infection; after 12 h incubation with virus the response declined to reach background levels at 24 h. Peritoneal cells from C57BL/6 mice which are relatively resistant to HSV-2 showed a higher respiratory burst capacity after infection than cells from more susceptible BALB/c mice. Incubation of macrophages with crude niurine interferon (IFN)-alpha/beta produced by macrophages or purified murine IFN-alpha, in concentrations comparable to those obtained early (2 to 5 h) after infection of macrophage cultures with HSV-2 also augmented the respiratory burst. Addition of an IFN-alpha/beta-specific antiserum to HSV-2-infected cultures almost completely removed the response. We therefore conclude that HSV-2 induces an early and genetically determined activation of macrophages, mediated in an autocrine manner by IFN-alpha/beta secreted by the macrophages early during infection.

Animals↗
PubMed1989

Differential sensitivity of macrophages from herpes simplex virus-resistant and -susceptible mice to respiratory burst priming by interferon-alpha/beta.

Herpes simplex virus primes mouse macrophages for a genetically determined respiratory burst mediated in an autocrine manner by interferon (IFN)-alpha/beta. We have analysed the effect of IFN-alpha/beta on the respiratory burst capacity of mouse peritoneal macrophages by luminol-dependent chemiluminescence using phorbol myristate acetate as trigger. Crude macrophage-produced IFN-alpha/beta as well as purified IFN-alpha and -beta regularly augmented the respiratory burst capacity of peritoneal cells in a concentration-dependent manner. The augmented response was exclusively mediated by macrophages and was manifest after 4 h incubation with IFN-alpha/beta, peaked after 8 h and gradually declined to near background levels after 24 h. The effect of macrophage-produced IFN-alpha/beta was completely abolished by preincubation of IFN with antiserum to IFN-alpha/beta. The data obtained with this antiserum indicated that endogenous IFN, undetectable by a standard cytopathic effect-inhibition assay, was sometimes spontaneously produced by the peritoneal cells. Furthermore, the crude macrophage preparation seemed to contain a macrophage deactivating factor counteracting the effect of IFN-alpha/beta. Genetic analysis of the sensitivity of macrophages for the respiratory burst-priming effect of IFN-alpha/beta revealed that the trait is inherited as a co-dominant autosomal feature. Macrophages from herpes simplex virus-resistant C57BL/6 mice were more sensitive than macrophages from virus-susceptible BALB/c mice and cells from mice of the reciprocal crosses showed an equal sensitivity intermediate between those of the parental strains. A physiological role of differential IFN sensitivity in the context of resistance to virus infections is suggested.

Animals↗
PubMed1988

Toxicity and ultrastructural localization of mercuric chloride in cultured murine macrophages.

The effects of mercuric chloride on cell survival, phagocytosis and cell migration were examined in cultured mouse peritoneal macrophages, and the accumulation of mercuric chloride in the cells was visualized by autometallography and evaluated by light and electron microscopy. Macrophages exposed to mercury concentrations from 1.25 microM to 10 microM mercuric chloride showed a concentration- and time-dependent increase in mercuric chloride accumulation, while cells exposed to 20 microM and 40 microM mercury showed an inverse relationship between mercury concentration and the accumulation of mercury. Mercury concentrations above these levels caused cell necrosis. Electron microscopy revealed that mercury was located primarily within lysosomes but also in the nucleus and cytoplasm. Mercury increased the death rate of macrophages in a concentration-dependent manner when cells were treated with mercury concentrations not causing cell necrosis. Further, we found that mercury clearly impaired macrophage random migration and possibly the capability for phagocytosis.

Animals↗
PubMed1988

Autocrine secretion of tumor necrosis factor under the influence of interferon-gamma amplifies HLA-DR gene induction in human monocytes.

Recombinant interferon-gamma (IFN-gamma) induced HLA-DR gene expression in both U937 and THP-1 human monocytic cell lines, although the former was only very weakly inducible. Combination of recombinant tumor necrosis factor (TNF) and IFN-gamma resulted in a synergistic enhancement of DR mRNA and protein induction in both cell lines. TNF alone increased the constitutive expression of the DR gene in THP-1 cells. In the HLA class II-negative U937 cells, TNF used alone was not able to induce DR gene expression. Such a negative result was not due to a lack of TNF receptor expression in U937 cells, since TNF clearly induced HLA class I and TNF gene expression in this cell line. THP-1, but not U937, cells secreted TNF under the influence of IFN-gamma. Neutralization of TNF by a specific antibody decreased IFN-gamma-induced DR antigen expression in THP-1 cultures. These observations indicate that TNF is not able to directly induce DR gene expression, but rather amplifies ongoing expression of this gene, whether constitutive or induced by IFN-gamma. In the two cell lines tested, the level of DR inducibility under the influence of IFN-gamma used alone depended on a different inducibility of TNF secretion by IFN-gamma. Altogether, our observations indicate that TNF, whether exogenous or endogenously produced under the influence of IFN-gamma, amplifies DR gene expression in monocytes, a phenomenon that may provide to such antigen-presenting cells a selective sensitivity to the DR-inducing effects of IFN-gamma.

Drug Synergism↗
PubMed1987

Autointerference in silver accumulation in macrophages without affecting phagocytic, migratory or interferon-producing capacity.

Silver accumulation and processing in mouse peritoneal macrophages was studied in vitro by autometallographic visualization of intracellular silver. During the first 24 h of incubation in a medium containing from 5 microM to 20 microM of silver lactate, an inverse relationship between silver concentration in the former and visualizable silver in macrophages was recorded. Later, however, the cells treated with higher silver concentrations accumulated most silver. Cells exposed to silver concentrations above these levels exhibited acute coagulation necrosis and disintegrated within the first 15 min of silver treatment. Macrophages treated with silver lactate concentrations not causing acute cytotoxicity showed no impairment of their phagocytic, migratory or interferon-producing capacities. The significance of autointerference in silver accumulation and processing in macrophages is discussed, and a functional defect in the lysosome/phagosome system is suggested as a basis for the phenomenon.

Animals↗
PubMed1986

X-linkage of the early in vitro alpha/beta interferon response of mouse peritoneal macrophages to herpes simplex virus type 2.

The genetics of the early interferon response of mouse peritoneal cells to infection with herpes simplex virus type 2 (HSV-2) was studied in susceptible BALB/c and more resistant C57BL/6 mice and in reciprocal crosses between these mice. Wash-outs of the peritoneal cavity of normal C57BL/6 mice contained significantly more cells than wash-outs from BALB/c mice. Therefore, interferon induction with HSV-2 was studied under standardized conditions in vitro. Peritoneal cells reacted to HSV-2 infection by interferon production in a virus dose-dependent manner. Interferon was detected first after 2 h and peaked after 24 h. Cells from C57BL/6 mice of each sex produced significantly more early interferon than cells from BALB/c mice, and cells from female BALB/c mice produced more interferon than cells from males. This difference was not seen with C57BL/6 mice. Cultures of highly purified adherent cells yielded approximately 10 times as much interferon as cultures of non-adherent cells. Since treatment of cells with carbonyl iron and silica significantly reduced the amount of interferon produced, whereas 2000 rad of irradiation had no obvious effect, it is concluded that the main interferon-producing cell in the peritoneal cavity of mice in response to HSV-2 is of the monocyte/macrophage lineage. Interferon production in peritoneal cells was found to be quantitatively influenced by X-linked loci in that cells from male (BALB/c female X C57 male) F1 mice, which inherit the X chromosome from the low-responding BALB/c females, produced significantly lower amounts of interferon than cells from the other three F1 generation genotypes. All interferons were characterized as alpha/beta interferon. It is suggested that the early production of alpha/beta interferon in response to HSV-2 is influenced by X-linked loci, which might be involved in sex-linked differences in resistance to human herpesviruses.

Animals↗
PubMed1986

Genetically determined difference in the antiviral action of alpha/beta interferon in cells from mice resistant or susceptible to herpes simplex virus type 2.

Resistance of mice to infection with herpes simplex virus type 2 (HSV-2) is genetically determined. Embryonic cells from susceptible BALB/c and resistant C57BL/6 mice were equally sensitive to infection with HSV-2 as judged by plaque area, plaquing efficiency, endpoint titration and virus yield. Cells from C57BL/6 mice showed a higher sensitivity than cells from BALB/c mice to the protective action of two preparations of alpha/beta interferon against challenge with HSV-2. This was evident both from c.p.e. inhibition and yield reduction experiments. The difference in sensitivity was dependent on virus dose and was greatest (up to 50-fold) with low virus doses. An analysis of the genetics of the alpha/beta interferon sensitivity in cells from embryos of parental mice and embryos derived from reciprocal matings between HSV-2-resistant and -susceptible mice suggested that interferon sensitivity is inherited as a co-dominant autosomal trait. The induction of the interferon-induced enzyme 2'-5'-oligoadenylate synthetase was also different in cells from the two mouse strains, since significant levels were only detected in cells from C57BL/6 mice. It is suggested that differential interferon sensitivity of cells from HSV-2-resistant and -susceptible mice might be a factor of importance for the course of the infection.

2',5'-Oligoadenylate Synthetase↗
PubMed1985

Genetic aspects of macrophage involvement in natural resistance to virus infections.

Macrophages are thought to constitute an important element in the body's natural defense against invasion and dissemination of viruses. Possible antiviral mechanisms of macrophages are defined and referred to as intrinsic, i.e. the ability of macrophages to serve as a nonpermissive barrier between the virus and susceptible cells and extrinsic, i.e. the ability of macrophages to affect the virus or virus replication in surrounding cells. Most studies on the role of macrophages in natural resistance to virus infections have been performed in animal models. An interesting aspect of many viral infections in animals is the finding of a genetically determined variation in natural resistance. Because of the availability of numerous inbred and congenic strains most studies on genetically determined resistance have been performed in mice. The classical examples are resistance to flaviviruses and susceptibility to mouse hepatitis virus, both of which are inherited as dominant, monogenic traits. With these viruses macrophage intrinsic restriction of virus replication has been found to express at the cellular level the genetics of resistance/susceptibility seen in the intact animal. Other examples, where macrophages have been implicated in genetically determined resistance include herpes simplex virus and influenza virus. The involvement of macrophages in natural resistance to these viruses is discussed in relation to other putative resistance determinants like interferon production and sensitivity and natural killer cell activity.

Animals↗
PubMed1985

Production of lymphokines and interferon by immune cells involved in recovery of mice from herpes simplex virus type 2 hepatitis.

Adoptive transfer of spleen cells from mice 4 days after infection with herpes simplex virus type 2 (HSV-2) reduced the virus titer in the liver of recipient mice infected 24 h before transfer. Macrophage chemotactic factor (CF) and macrophage migration inhibition factor (MIF) were produced by day 3 of infection in spleen cell cultures stimulated with HSV-2, but not with control antigen, i.e. 1 day before the cells are active in adoptive transfer. Interferon was produced in cultures established throughout the infection but not in normal spleen cells. From days 1 to 5 of infection interferon was produced irrespective of in vitro restimulation, although the highest amounts were always produced after stimulation with the specific antigen. Spleen cells from mice infected for 6 days produced interferon only when stimulated with HSV-2. The cells from 6-day-immune mice active in adoptive transfer and CF and MIF production were found to be Thy 1+, Ig- and Lyt2-. Both Thy 1+ and plastic adherent cells were necessary for interferon production, whereas Ig+ and Lyt2+ cells did not produce interferon. The interferon was acid stable and neutralized by antiserum against alpha/beta-interferon and thus has the characteristics of alpha-interferon. The data indicate that a delayed type hypersensitivity reaction with lymphokine-induced macrophage recruitment into infectious foci may be a central feature of the recovery process in HSV-2-induced hepatitis. A possible role of interferon produced by the accumulated cells needs further investigation.

Animals↗
PubMed1985

Experimental mastitis in mice induced by coagulase-negative staphylococci isolated from cases of mastitis in nursing women.

Coagulase-negative staphylococci are frequently isolated from the milk of women with signs of puerperal mastitis. In order to evaluate the pathogenicity of these bacteria, strains of S. epidermidis and S. saprophyticus isolated from cases of mastitis in nursing women were inoculated into the mammary glands of lactating mice. Although clinical signs of mastitis were absent, by histological examination, mastitis was demonstrated in 78-93% of the glands. Abscesses were found in a few cases only. The inoculated bacteria were re-isolated in 41-61% of the cases, and when inoculated in numbers of 10(2) to 10(4) c.f.u. the bacteria multiplied above input levels in several cases. It is concluded that coagulase-negative staphylococci isolated from the milk of women with puerperal mastitis can produce mastitis in mice and should be considered as a possible etiologic agent of mastitis in nursing women.

Animals↗
PubMed1985

Mouse peritoneal cells exposed to sodium aurothiomalate in vivo.

The localization of gold in normal, stimulated and activated mouse peritoneal cells exposed in vivo to sodium aurothiomalate was examined by a new histochemical technique based on physical development. Activated macrophages from mice infected with herpes simplex virus type II showed the greatest amount of gold localized within lysosomes. Mast cells contained gold in their granules. Polymorphonuclear leucocytes and lymphocytes, on the other hand, were devoid of gold. Pinocytosis is discussed as the mechanism by which gold is taken up into the cells.

Animals↗
PubMed1984

Ultrastructural localization of gold in macrophages and mast cells exposed to aurothioglucose.

The ultrastructural localization of gold in resting, stimulated, and activated mouse peritoneal cells exposed in vivo and in vitro to aurothioglucose was examined by a photochemical technique. Activated macrophages from herpes simplex virus type 2 infected mice showed the heaviest accumulation of gold, located in phagolysosomes. Gold was also visualized in granules of mast cells and in nuclei of disintegrated cells. No gold was found in polymorphonuclear leucocytes and in lymphocytes. The mechanism by which gold is taken up into the cells is discussed.

Animals↗