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Biomedical subjects

C O Solberg

Publications and source records attributed to C O Solberg.

At least 37 records · Page 2Linked to original sources

Isoprinosine stimulates granulocyte chemiluminescence and inhibits monocyte chemiluminescence in vitro.

Isoprinosine may delay disease progression in human immunodeficiency virus infection, presumably through modulation of lymphocyte function. However, the influence of isoprinosine on phagocyte function is largely unknown. This study describes the effects of isoprinosine and azidothymidine on phagocyte chemiluminescence and migration. Incubation with isoprinosine concentrations of 250 micrograms/ml and above increased the chemiluminescence of granulocytes. Random migration of granulocytes was decreased at isoprinosine concentrations of 50 micrograms/ml and higher, but chemotaxis was not affected. Azidothymidine exerted no effect on the chemiluminescence or migration of granulocytes. For monocytes, luminol-enhanced chemiluminescence was reduced at isoprinosine concentrations of 250 micrograms/ml and above, whereas migration was not affected. These findings suggest that the immunomodulatory properties of isoprinosine may extend to phagocytic cells. This may be of significance in the treatment of immunodeficiency states.

Cell Movement↗

Humoral immune response to class 1 outer membrane protein during the course of meningococcal disease.

We have determined the amounts of specific anti-class 1 outer membrane protein antibodies in sera from 25 patients during the course of systemic meningococcal disease, using purified class 1 protein as the sensitizing antigen in an enzyme-linked immunosorbent assay. The class 1 protein was obtained from a variant of strain 44/76 (B:15:P1.7,16) lacking class 3 and class 4 outer membrane proteins. Specific anti-class 1 (serosubtype P1.7,16) outer membrane protein immunoglobulin G (IgG) antibody levels increased significantly in 12 patients (12 of 25; 48%), regardless of the serotype of the infecting strain, indicating that the antibodies reacted in part with epitopes not determined by the monoclonal antibodies used for serotyping. Most patients had low levels of anti-class 1 IgG antibodies during the acute illness. The antibody levels peaked during the second week of disease and returned to near baseline levels in sera collected 6 weeks to 12 months after the onset of the disease. The majority of the specific anti-class 1 IgG antibodies bound to surface-exposed epitopes on whole bacteria and belonged to the IgG1 and IgG3 subclasses. Anti-class 1 IgA and IgM antibodies were not detected in any of the patient sera. Prior to disease, seven patients had been immunized with a meningococcal outer membrane vesicle vaccine developed from strain 44/76 (P1.7,16). None of these patients was infected with meningococcal strains containing class 1 protein homologous or partly homologous to that of the vaccine strain, indicating serosubtype-specific protection. The highest anti-class 1 IgG antibody peak levels were seen in immunized patients infected with strains of heterologous serotype, suggesting an anamnestic response. However, these patients were not protected from meningococcal disease after immunization.

Adolescent↗

Cross-reacting serum opsonins to meningococci after vaccination.

The opsonic activity of sera from healthy volunteers immunized with an outer membrane vesicle vaccine prepared from a Neisseria meningitidis (class 3, 44/76, B:15:P1.7,16), characteristic of the present Norwegian epidemic, has been examined. A marked increase in the phagocytosis of class 3 and nontypeable strains of different serogroups, serotypes, and serosubtypes was demonstrated in the presence of postvaccination sera. Sera from vaccinees also caused a significant increase in leukocyte oxidative metabolism as measured by luminol-enhanced chemoluminescence during phagocytosis of class 3 and nontypeable meningococci. An increase in serum opsonins cross-reacting with class 2 (type 2a) meningococci of different serogroups was not observed, suggesting that future meningococcal outer membrane vesicle vaccine preparations should contain both class 2 and class 3 porins in geographic areas where both class 2 and class 3 strains cause disease.

Antibodies, Bacterial↗

Cross-reacting serum opsonins in patients with meningococcal disease.

We have examined the opsonic activity of sera from patients with Neisseria meningitidis (B:15:P1.16) infections against different meningococcal strains, using flow cytometry and luminol-enhanced chemiluminescence. A marked increase in the phagocytosis of ethanol-fixed meningococcal strains of different serogroups, serotypes, and serosubtypes was demonstrated in the presence of convalescence sera compared with acute sera. Convalescence sera also caused a significant increase of leukocyte oxidative metabolism during phagocytosis, as measured by luminol-enhanced chemiluminescence. The sera contained a broad range of opsonins cross-reacting with serogroup A, B, C, W-135, and Y meningococci of different serotypes and serosubtypes, indicating that the cross-reacting opsonins recognized surface epitopes other than those determined by current serotyping schemes.

Adolescent↗

Negative selection of human monocytes using magnetic particles covered by anti-lymphocyte antibodies.

We have developed a standardized procedure for the isolation of monocytes from peripheral blood by negative selection using magnetic polymer particles coated with monoclonal antibodies against T and B lymphocytes. The average purity of the monocyte suspension was 85%, and monocyte recovery was 72% from Ficoll-Hypaque gradient separated mononuclear cells and 32% from whole blood. In a lucigenin enhanced chemiluminescence assay there was no significant difference between cells separated immunomagnetically and those separated on a gradient. Nor did electron microscopy show any significant difference in morphology between such monocytes. Negative selection using magnetic polymer particles is an efficient method for the separation of monocytes with intact morphology and function as measured by chemiluminescence.

Antibodies, Monoclonal↗

[Viral infections in immunocompromised patients].

An increasing number of patients are immunocompromised due to modern treatment of cancer, organ transplantations and HIV-infections. Opportunistic viral infections are common and may cause serious disease among these patients. New vaccines, immunomodulators and antiviral drugs make it possible to prevent and treat many of these infections. We review the host defence against viral infections and the most important viral infections. We also discuss prophylaxis, diagnosis and therapy.

Antiviral Agents↗

Effect of fusidic acid on migration and chemiluminescence of polymorphonuclear leukocytes.

Incubation of polymorphonuclear leukocytes (PMNs) in fusidic acid resulted in a decrease of random migration and chemiluminescence. The effects were dose-dependent but moderate, with statistical significance only at concentrations of 50 mg/l or more. At concentrations used for therapy of bacterial infections and AIDS, fusidic acid was not shown to be deleterious to these aspects of PMN function.

Acquired Immunodeficiency Syndrome↗

IgG subclass antibodies to serogroup B meningococcal outer membrane antigens following infection and vaccination.

IgG and IgG subclass antibodies to the outer membrane antigens from Neisseria meningitidis (serogroup B, serotype 15:P1.16) were quantitated by an enzyme-linked immunosorbent assay (ELISA) in sera from 40 patients with group B:15:P1.16 meningococcal disease and 24 volunteers immunized with a serotype 15:P1.16 outer membrane vesicle vaccine. A second injection was given 6 weeks after the first immunization. Patient sera obtained two and six weeks after onset of the disease had significantly higher levels of total IgG, IgG1, IgG2, and IgG3 antibodies to the outer membrane antigens than acute sera, convalescent sera from patients with systemic non-meningococcal bacterial infections and sera from healthy controls. The levels of total IgG and IgG1 remained high one and three years later. Sera from the vaccinees showed high levels of total IgG and IgG1 6, 12 and 26 weeks after the first immunization and high levels of IgG3 6 weeks after the second immunization. No increase of IgG2 or IgG4 levels was observed in the postimmunization sera. Immunoblotting of three convalescent sera demonstrated individual patterns of IgG subclass binding to various outer membrane antigens with most distinct binding of IgG1 and IgG3 antibodies to the class I protein, the H.8 lipoprotein and the lipopolysaccharide. Since IgG1 and IgG3 are the most effective antibodies for complement activation and phagocytosis, group B meningococcal disease and immunization with the serotype 15:P1.16 outer membrane vesicle vaccine stimulate production of those IgG subclasses which have the strongest opsonic and bactericidal activity.

Adolescent↗

Two-layer gradient separation of granulocytes for functional tests.

Two gradient separation techniques were compared with the dextran sedimentation method for the separation of granulocytes from blood. Both techniques gave adequate yield and excellent purity, and flow cytometric analysis of surface membrane markers gave no indication of subset selection during the procedure. Cells separated by the three methods behaved comparably in functional tests including random migration, chemotaxis and chemiluminescence. The gradient separation techniques are rapid and efficient methods for the preparation of near 100% pure granulocyte suspensions for functional studies.

Cell Movement↗

Flow cytometric assay for the measurement of serum opsonins to Neisseria meningitidis serogroup B, serotype 15.

A flow cytometric phagocytosis assay has been developed for the measurement of human serum opsonins to serogroup B meningococci. Live bacteria and bacteria inactivated by heat, formalin or ethanol were labelled with fluorescein-isothiocyanate (FITC). The bacteria were opsonized with sera from patients with group B meningococcal disease and sera from healthy controls, and phagocytosis determined by combined measurements of FITC-fluorescence and forward angle light scatter. Optimal sensitivity was obtained using viable bacteria, 5% serum, 20 bacteria per leukocyte capable of phagocytosis, 7.5 min opsonization time, 5 min phagocytosis time, 37 degrees C, and continuous agitation during opsonization and phagocytosis. The opsonic activity of sera from convalescent patients was markedly higher than that of sera from patients with acute illness. Only minor day-to-day and interindividual variations were observed. The flow cytometric phagocytosis technique is a rapid and reproducible method for the measurement of serum opsonins to meningococci.

Blood Bactericidal Activity↗

Effects of clindamycin and cefuroxime on leukocyte membrane receptors and function.

Normal human granulocytes and lymphocytes were preincubated in 0.5, 5, or 50 mg/l of clindamycin, and 5, 50, or 500 mg/l of cefuroxime. Incubation with clindamycin caused an increase in the proportion of granulocytes bearing receptors for the Fc portion of IgG (Fc gamma-R) and C3b (C3b-R). Random migration in capillary tubes was significantly decreased, but phagocytosis as measured by chemiluminescence was only slightly decreased. The proportion of lymphocytes bearing Fc gamma-R was decreased, while there was no effect on lymphocyte C3b-R percentage, nor on the proportion of granulocytes or lymphocytes bearing sheep erythrocyte (E) receptors. Preincubation of granulocytes in cefuroxime was not associated with changes in the proportion of receptor-bearing cells, except for a slight increase in Fc gamma-R-bearing lymphocytes at the lowest concentration tested. Tube migration was not affected but chemiluminescence was significantly decreased. Preincubation with clindamycin, although increasing the proportion of cells bearing phagocytosis-associated receptors, is thus not associated with an increased phagocytic ability, while cefuroxime incubation caused a decrease in chemiluminescence despite normal levels of receptor-positive cells.

Antigens, Differentiation↗

Serum opsonins to serogroup B meningococci in meningococcal disease.

The opsonic activity to serogroup B meningococci (B:15:P1.16) was measured in sera from 101 patients with meningococcal disease using a chemiluminescence method. On admission to hospital the opsonic activity was lower in 12 patients who died than in survivors (p = 0.0007). A close association was observed between the opsonic activity and the duration of symptoms before admission, the severity of the disease, and the levels of IgG antibodies to the outer membrane complex (15:P1.16). The opsonic activity was low in 2 premorbid sera compared to healthy controls. The mean opsonic activity peaked 2 weeks after admission and was still high 3-5 years later. Meningococcal strains of different serogroups, serotypes and subtypes induced a similar increase in opsonic activity to B:15:P1.16 meningococci. No increase in activity was observed in sera from patients with meningitis and septicemia caused by other bacteria. Serum opsonins seem to be of significant importance in the host defence against serogroup B meningococci.

Adolescent↗

Effects of two macrolide antibiotics on human leukocyte membrane receptors and functions.

Polymorphonuclear granulocytes (PMNs) and lymphocytes from healthy persons were incubated in varying concentrations of erythromycin and RU 28965, a new macrolide antibiotic. Incubation in erythromycin - even in high dilutions - caused a significant increase in the percentage of PMNs bearing receptors for the Fc portion of IgG (Fc gamma R) and for C3b (C3bR) as measured by rosette formation with EA (erythrocyte-antibody) and EAC (erythrocyte-antibody-complement) indicator cells. This effect could not be removed by extended washing of the cells. Incubation in RU 28965 had a similar effect, except for a decrease in EA and EAC rosetting cells at high concentrations (200 mg/l). Phagocytosis, as measured by chemiluminescence, and random migration of PMNs were unaffected by erythromycin. Chemotaxis under agarose was decreased after incubation in erythromycin or RU 28965. Erythromycin incubation increased the percentage of lymphocytes bearing receptors for sheep erythrocytes (E), but had no effect on the proportion of lymphocytes rosetting with EA or EAC, or on lymphocyte responses to mitogens PHA, conA, or PWM.

Chemotaxis, Leukocyte↗

Infective endocarditis 1973-1984 at the Bergen University Hospital: clinical feature, treatment and prognosis.

During the period 1973-1984, 72 patients with infective endocarditis (IE) were hospitalized in the medical department, Bergen University Hospital. The male/female ratio was 1.25/1, the mean age 55.3 years. 35 infections were caused by streptococci, 18 by staphylococci, 6 by other microorganisms and in 13 cases no causal organism was found. Only 13 patients had rheumatic heart disease. The overall mortality was 35%, and the mean age of the patients who died was 65 years. The case fatality rates for staphylococcal and streptococcal endocarditis were 61 and 24% respectively. In the period 1973-1978 the case fatality rate was 50% compared to 26% during 1979-1984. The proportion of patients with culture-negative endocarditis was reduced from 31 to 11% from the first to the second half of the study and the percentage of patients who received antibiotics before diagnosis decreased from 81 to 58%. Valve replacement was performed in 4 patients with staphylococcal and 15 with streptococcal infections. Seven cases (mean age 73.4 years) were diagnosed at necropsy; 3 with staphylococcal infections. With increased clinical awareness of IE, liberal use of blood cultures, better diagnostic tools and earlier surgical intervention, especially in staphylococcal infections, a further reduction in mortality should be possible.

Age Factors↗

Inhibition of in vitro lysozyme release from human granulocytes and monocytes by non-steroidal anti-inflammatory agents.

A selective zymosan-induced release of lysozyme from freshly prepared human blood granulocytes and monocytes was inhibited by indomethacin, sulindac, piroxicam and ibuprofen. This effect was slightly more marked for granulocytes than for monocytes. Salicylic acid, acetylsalicylic acid and naproxen, even at high concentrations, did not inhibit the enzyme release from either cell type. Since all these nonsteroidal anti-inflammatory agents are cyclooxygenase inhibitors, these findings suggest that lysozyme release is independent of prostaglandin biosynthesis.

Anti-Inflammatory Agents, Non-Steroidal↗