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Biomedical subjects

C O Solberg

Publications and source records attributed to C O Solberg.

At least 73 records · Page 4Linked to original sources

In vitro release of lysozyme from monocytes and granulocytes.

When exposed to zymosan or latex particles or heat-inactivated staphylococci, freshly prepared human blood monocytes and granulocytes rapidly released a large fraction of their lysozyme content. Within 24 hours the total lysozyme activity in the monocyte suspensions tripled, while it doubled in the granulocyte suspensions, indicating synthesis of the enzyme following release. The monocytes in particular seemed to release and synthesize lysozyme without any other stimulus than contact with lymphocytes and the tube walls. Potassium caseinate in solution did not influence the lysozyme release. Myeloperoxidase and beta-glucuronidase, which in the granulocytes are kept in lysosomal fractions separate from most of the lysozyme, were neither released nor synthesized to a significant degree. Moreover, the minute amount of lactate dehydrogenase released indicated that the lysozyme release was not the result of cell lysis. Accordingly, the monocytes, which are not already stimulated by adherence to nonphagocytosable surfaces, are capable of selective enzyme release similar to that of the granulocytes.

Glucuronidase↗

The pharmacokinetics of ceftriaxone in serum, skin blister and thread fluid.

Following 4 g of ceftriaxone, given intravenously, to eight volunteers, the antibiotic concentration in serum, suction skin blister fluid and fluid from subcutaneously implanted threads was followed for 28 h. High and sustained levels were found in both serum and extravascular fluids; the mean maximum serum concentration was 448 mg/l, and the mean peak concentrations in blister and thread fluid were 94 mg/l and 63 mg/l, respectively. The terminal, half-lives were: serum 7.2 h, blister fluid 10.3 h and thread fluid 11.3 h. The total area under the concentration versus time curves for serum was 1636 mg X h/l. For blister and thread fluid the areas were 1573 mg X h/l and 808 mg X h/l. The results suggest a twice daily dosage regimen.

Adult↗

Decrease of Fc gamma and C3b receptor-bearing granulocytes and of T lymphocytes in myelomatosis.

18 patients with myelomatosis had lower percentages of granulocytes bearing receptors for Fc gamma (47.6%) and C3b (43.0%) than controls (80.4% and 75.0%). The percentage of T lymphocytes was decreased in patients when untreated sheep erythrocytes were used as indicator cells. Patients with high serum IgG levels had lower percentages of T lymphocytes. There was no significant difference in receptor profile between treated and untreated patients. The decrease in Fc gamma and C3b receptor-bearing granulocytes in myelomatosis is probably not due to serum or plasma factors since (a) the distribution of receptor-bearing lymphocytes was not different from that of the controls; (b) extra washings of cells or overnight incubation did not enhance the percentage of receptor positive cells; and (c) incubation of normal granulocytes in sera or plasma from myelomatosis patients did not cause a more pronounced reduction in the proportions of Fc gamma of C3b receptor-bearing cells than incubation in normal sera or plasma.

Aged↗

Phagocytosis of Staphylococcus aureus by human leukocytes: quantitation by a flow cytometric and a microbiological method.

Phagocytosis of killed, fluorochrome stained or live Staphylococcus aureus by human leukocytes was measured by flow cytometry (FCM) or a microbiological method, respectively. The results were compared to those obtained by simulation using a prey-predator model. In the presence of an initial bacteria-to-phagocyte ratio of 4:1 to 160:1, the percentage of phagocytosing leukocytes was independent of the bacteria and phagocyte concentration. The number of phagocytosed or killed bacteria per phagocyte increased with increasing bacteria and decreasing phagocyte concentration. One per cent pooled human serum was sufficient for maximum phagocytosis to occur, but killing slightly increased in the presence of 10% pooled human serum. With medium or low initial bacteria-to-phagocyte ratios phagocytosis and killing closely corresponded to the results obtained by the prey-predator model. Maximally each phagocyte was associated with 80 bacteria (measured by FCM), about 45 being phagocytosed (internalized) and 40 killed. The model seems suitable for the simulation of phagocytosis and killing of S. aureus by human leukocytes.

Adhesiveness↗

The influence of harvesting intervals on chemiluminescence and enzyme activities of rat peritoneal leukocytes.

Rat leukocytes were obtained from the peritoneal cavity by stimulation with potassium caseinate. The chemiluminescence response of the polymorphonuclear leukocytes exposed to opsonized zymosan was influenced by the interval between instillation of caseinate and harvesting of the cells. With intervals increasing from four to 72 hours, the maximum activity was reached after 24 hours. The myeloperoxidase activity of all the leukocytes together increased gradually up to 72 hours after instillation of caseinate. After exposure to zymosan particles, only a negligible fraction of this enzyme was released from the cells. On the other hand, the lysozyme activity was highest in cells harvested early, and a large fraction of this enzyme was also released from these cells. The findings emphasize the importance of standardized conditions for stimulation and harvesting of rat peritoneal leukocytes.

Animals↗

Influence of tetracyclines on human polymorphonuclear leukocyte function.

Low concentrations of oxytetracycline, doxycycline, or minocycline (less than 10 micrograms/ml) did not influence in vitro polymorphonuclear leukocyte random migration, chemiluminescence, or glucose oxidation. At high concentrations of doxycycline or minocycline (greater than 10 micrograms/ml), chemiluminescence and glucose oxidation were impaired. High concentrations of doxycycline also reduced random migration. Oxytetracycline did not influence these functions in concentrations up to 100 micrograms/ml. The inhibiting effect of doxycycline and minocycline was abolished when 4 mM Mg2+ was added to the reaction mixture, and 4 mM Ca2+ partly restored minocycline-inhibited polymorphonuclear leukocyte functions. This indicates that the major effect of tetracyclines on in vitro polymorphonuclear leukocyte functions is mediated by their divalent cation chelating effect and that the results of in vitro experiments are highly dependent on the concentration of divalent cations in the reaction mixtures. The difference between the tetracyclines may be due to differences in lipid solubility, with solubility being highest for minocycline and lowest for oxytetracycline, or to different divalent cation chelating ability.

Cations↗

Effect of tetracyclines and UV light on oxygen consumption by human leukocytes.

When polymorphonuclear leukocytes were stimulated with zymosan, a sharp rise in oxygen consumption was observed. In the presence of doxycycline, we observed a further increase in oxygen consumption when the phagocytosing cells were exposed to UV light. When the light was turned off, oxygen consumption of the cells almost ceased, indicating photodamage to polymorphonuclear leukocytes during irradiation. Irradiation of the polymorphonuclear leukocytes for 20 min in the presence of doxycycline (10 micrograms/ml) before phagocytosis completely abolished the rise in oxygen consumption initiated by zymosan. Demethylchlortetracycline and light exposure also caused a marked reduction of polymorphonuclear leukocyte oxygen consumption, whereas oxytetracycline, lymecycline, chlortetracycline, and minocycline had only a slight or no photosensitizing effect. The photodamage induced by doxycycline and demethylchlortetracycline was inhibited by azide and enhanced in deuterium oxide. This was in accordance with singlet oxygen-mediated damage.

Humans↗

Human opsonins to meningococci after vaccination.

Two groups of volunteers were immunized with either a serogroup A plus C meningococcal polysaccharide vaccine or a combined serogroup B polysaccharide-serotype 2 protein vaccine. Serum opsonin responses were measured by chemiluminescence of polymorphonuclear leukocytes exposed to opsonized live meningococci. Two of the six volunteers immunized with the A plus C vaccine had an increase in serum opsonins to group A meningococci, four responded to group C meningococci, and none to group B meningococci. Five other volunteers who were immunized with the combined group B polysaccharide-serotype 2 protein vaccine responded with an increase in serum opsonins to group B meningococci of two different protein serotypes, as well as to a group C-serotype 2 meningococcal strain. Although no booster effect was observed after a second dose of the combined vaccine, both the polysaccharide and the protein components appear to be able to stimulate an opsonin response.

Bacterial Vaccines↗

Phagocytic cells in host defence.

The normal response of phagocytic cells to microbial invasion may be divided into three interrelated phases: the recognition and migration of the phagocytes to the site of infection, the phagocytosis or ingestion of the microorganisms and the cellular and metabolic factors involved in the killing of the microorganisms. A wide spectrum of clinical disorders, characterized by enhanced susceptibility to infection, has been related to defects in any of these functions. Furthermore, for every step of phagocyte response to infection, a mechanism seems to exist by which the microorganisms can avoid the injurious consequences of their interactions with normal phagocytes. The interactions between normal and defective phagocytes and microorganisms are presented.

Bacteria↗

Treatment of acute bacterial meningitis with special emphasis on beta-lactam antibiotics.

Acute bacterial meningitis still represents a therapeutic problem. Successful management depends on early administration of large doses of bactericidal antibiotics and adequate treatment of complications, i.e. shock, acute cerebral edema, consumption coagulopathy, convulsions and electrolyte disturbances. Meningitis caused by Neisseria meningitidis or Streptococcus pneumoniae should be treated with benzylpenicillin. If benzylpenicillin cannot be given, chloramphenicol has remained the best substitute. However, cefuroxime or ceftriaxone now seems to offer an alternative to chloramphenicol. The prevalence of beta-lactamase-producing Haemophilus influenzae strains is increasing and chloramphenicol has replaced ampicillin in the treatment of H. influenzae meningitis. Recent studies indicate that cefuroxime, ceftriaxone or moxalactam may be as effective as chloramphenicol in this type of meningitis. In neonatal meningitis, cefotaxime or moxalactam may constitute alternatives to the present regimens with ampicillin-gentamicin, gentamicin-chloramphenicol, cotrimoxazole or gentamicin. Promising results have also been obtained with cefotaxime or moxalactam in elderly patients with meningitis due to Gram-negative enteric bacilli. However, more extensive studies are needed to determine the role of the newer cephalosporins in the treatment of acute bacterial meningitis.

Anti-Bacterial Agents↗

Simultaneous measurement of phagocytosis and phagosomal pH by flow cytometry: role of polymorphonuclear neutrophilic leukocyte granules in phagosome acidification.

Human polymorphonuclear neutrophilic leukocytes (PMNLs) phagocytosed fluorescein-isothiocyanate (FITC)-labelled Staphylococcus aureus. Free bacteria, phagocytes, and nonphagocytes were discriminated and quantified by flow cytometry (FCM). The relative fluorescence of phagocyte-associated and free bacteria (Nf:N) was calculated by dividing the mean phagocyte fluorescence by that of the free bacteria and the number of phagocytosed bacteria. Bactericidal capacity and chemiluminescence were measured by standard methods. The red-to-green fluorescence ratio of acridine orange-stained PMNLs (R/G) was measured by FCM. Degradation of bacteria was monitored by the reduction in FITC and ethidiumbromide fluorescence of bacteria liberated from the phagocytes. Bacterial FITC fluorescence was pH dependent. Nf:N was 0.5 to 0.7. Using a standard curve for the interrelationship between bacterial fluorescence and pH, phagosomal pH was 5.0-5.5. Phagocytes, kept at 4 degrees C for 24 h had Nf:N approximately 1, did not degrade bacteria, but killed them and emitted chemiluminescence. NH4Cl increased phagocyte fluorescence by 27% and decreased R/G by 50%. Cyanide and azide did not affect Nf:N. Nf:N of phagocytes from a patient with chronic granulomatous disease was 32% below, and R/G was 32% higher than the controls. Acidification of the phagosomes seems to be related to discharge of PMNL granule contents and independent of the respiratory burst.

Acridine Orange↗

Granulocyte function in malignant monoclonal gammopathy.

Granulocyte function was studied in 22 patients with untreated myelomatosis or macroglobulinaemia. Granulocyte adhesiveness (GA) and migration in capillary tubes (Tm) were, except for light chain disease, significantly decreased in patients of all gammopathy classes especially IgG myelomatosis. A plasma factor inhibited GA. The impairment of Tm was due to an inhibiting factor as well as lack of a stimulating plasma factor. Migration of granulocytes to skin chambers was decreased in patients with IgG myelomatosis. Chemiluminescence production during phagocytosis of opsonized zymosan was decreased. Compared to control sera, the opsonic activity of patient sera was strongly decreased. The impaired granulocyte functions in patients with malignant monoclonal gammopathy may contribute to the enhanced susceptibility to infections in these patients.

Aged↗

Phagocytosis of bacteria by human leukocytes measured by flow cytometry.

A new method has been developed for the evaluation of the phagocytic activity of human leukocytes using fluorescently labeled bacteria and flow cytometry. By simultaneous measurement of cellular light scatter and fluorescence, extracellular bacteria, phagocytes, and nonphagocytes could be discriminated and quantified. All leukocytes assumed to be capable of phagocytosis were phagocytosing, and about 90% of these cells were polymorphonuclear neutrophilic granulocytes. Within 15 min 85% of the bacteria were phagocytosed and each phagocyte contained an average of 15-20 bacteria. The phagocytic capacity of the leukocytes from healthy individuals showed minor interindividual and day-to-day variations. This method facilitates a rapid and accurate in vitro evaluation of the phagocytic activity of human leukocytes.

Bacteria↗

Therapy of staphylococcal septicaemia in compromised hosts.

Despite advances in antibiotic therapy, infection remains one of the major causes of death in compromised patients, and the severity of the underlying disease often determines the outcome of the infectious disease. During a 5-year period (July 1, 1974--June 30, 1979), septicaemia was diagnosed in 604 patients admitted to Haukeland Hospital, and 175 (29%) of these patients died. 640 septic episodes occurred in the 604 patients, and 684 bacterial strains were isolated from the blood. Staphylococcus aureus and Staphylococcus epidermidis accounted for 96 (14%) and 45 (6.6%) of the causative strains, respectively. 85 patients had septicaemia caused by S. aureus and 40 by S. epidermidis. 19 (22.4%) patients with S. aureus septicaemia and 9 (22.5%) with S. epidermidis septicaemia died. 12 of 21 (57%) patients with S. aureus or S. epidermidis septicaemia and underlying malignant disease died and only 16 of 104 (15%) patients with staphylococcal septicaemia and non-malignant disease. More than 96% of the S. aureus strains were susceptible to isoxazolylpenicillins, cephalothin, lincomycin or gentamicin, but only 18% to benzylpenicillin. The S. epidermidis strains were less susceptible to lincomycin and gentamicin. Single antibiotic treatment (a penicillin, cephalosporin or vancomycin) seemed as effective in staphylococcal septicaemia as combined penicillin/aminoglycoside therapy or other combinations. In compromised patients staphylococcal septicaemia is often fulminant, and antimicrobial therapy must be started as soon as specimens for microbiological cultures are obtained. So far, there is no clinical proof that antibiotic combination therapy is superior to single drug treatment. However, if penicillins can not be used or the response to single drug therapy is poor, combination therapy should be considered.

Anti-Bacterial Agents↗