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Biomedical subjects

A Forsgren

Publications and source records attributed to A Forsgren.

At least 145 records · Page 8Linked to original sources

Characterization of interferons induced by bacteria and interferon-producing leukocytes in human peripheral blood.

All of 23 different preparations of formaldehyde-fixed and heat-killed bacteria induced the appearance of high levels of interferon (IFN) in cultures of human peripheral blood mononuclear leukocytes. Some bacteria induced peak IFN titers after 24 h of culture, whereas other bacteria showed maximal titers on culture days 2 to 3. The IFN displayed various properties. One type, which appeared early during the cultures, had characteristics of IFN-alpha, being resistant to pH 2 treatment but neutralized by antibodies to IFN-alpha. A second type, which appeared later, on culture days 2 to 3, resembled IFN-gamma in being sensitive to pH 2 treatment but resistant to anti-IFN-alpha antibodies. A third type, which appeared to be sensitive to both pH 2 and antibody treatment, was interpreted as atypical IFN-alpha. The application of cell fractionation procedures indicated that nonadherent, predominantly Fc receptor-bearing, non-T, non-B cells were producers of IFN-alpha as defined by its antigenic properties. They copurified approximately with cells carrying natural killer activity toward human erythroid leukemia K562 cells. Some bacteria apparently also stimulated T lymphocytes to produce material with properties of IFN-gamma.

Antibodies, Viral↗

Comparison of skin blisters and implanted cotton threads for the evaluation of antibiotic tissue concentrations.

The skin blister technique and a new technique using subcutaneously implanted cotton threads for the evaluation of antibiotic tissue concentrations were compared. Six volunteers received 2 g ampicillin and, after at least one week, 1 g of cloxacillin intravenously. Samples of serum, blister fluid and thread fluid were analysed by an agar well diffusion technique. The half-life of ampicillin and cloxacillin was prolonged in blister fluid compared to serum and thread fluid. Our conclusions are that the thread technique might reflect the kinetics of antibiotics in extracellular fluid where the penetration mostly depends on serum protein binding of the drug. The blister technique on the other hand might resemble the conditions in different subcutaneously implanted cages, fibrin clots and even abscesses where factors such as time and volume of the extracellular compartments also strongly influence the distribution of antibiotics.

Adult↗

Influence of beta-adrenoceptor blocking agents on lymphocyte function in vitro.

1 In order to assess whether beta-adrenoceptor blocking agents may have an immunomodulatory influence, the in vitro effect of propranolol metoprolol and atenolol on mitogenic activation of human peripheral blood lymphocytes was studied. To investigate further the mechanism of this influence, the effects of quinidine and two other membrane stabilizing agents were examined. 2 At 100 and 1000 mumol/l, both (+)-propranolol, (-)-propranolol and (+/-)-propranolol evoked a strong reduction of mitogenic lymphocyte activation. A similar effect was obtained with quinidine. Even at 1000 mumol/l metoprolol, had only a slight suppressive effect and atenolol had no suppressive influence at all. 3 It appears that propranolol may suppress mitogenic activation of lymphocytes, and that the effect may be ascribed to membrane stabilization rather than to beta-adrenoceptor blockade.

Adrenergic beta-Antagonists↗

Enzyme-linked immunosorbent assay (ELISA) for antibodies against Campylobacter jejuni, and its clinical application.

Antibody response to Campylobacter jejuni/coli (CJC) was investigated, using an enzyme-linked immunosorbent assay, ELISA. With a mixture of lipopolysaccharide from two CJC strains as antigen in ELISA, all 24 tested rabbit anti-CJC sera showed high antibody levels. However, only 70% of sera from patients with Campylobacter enteritis demonstrated an antibody response against the combined LPS antigen, using paired sera. In addition, the results obtained suggested non-specific binding of human immunoglobulin. When 24 formalinized whole CJC bacteria were used as antigen in ELISA, all corresponding rabbit antisera reacted with one strain (M 14). Essentially no unspecific binding of human immunoglobulin was obtained. Antibodies were detected in sera from healthy blood donors and at a lower level in sera from children, suggesting early immunization. In 67 enteritis patients with positive stool cultures for CJC, a significantly increased level of IgG antibodies could be detected in single or paired serum samples from 82% of the patients. An IgG titre increase occurred early in the course of infection, suggesting a boosting of an earlier immunization. IgM antibodies could be detected in the same sera in 77% of the patients. Considering both IgG and IgM analyses of the enteritis sera, 94% of the patients were positive in Campylobacter ELISA serology compared with only 5% of healthy controls.

Adult↗

Suppressor T lymphocyte function in Graves' disease.

To explore suppressor T lymphocyte function in Graves' disease, studies were performed in one group of patients in the hyperthyroid state and in another group in the euthyroid state after treatment. Peripheral blood lymphocytes were cultured for 1-7 days. Pokeweed mitogen (PWM; 1.25 micrograms/ml) was added at the initiation of the cultures or after 24 h. The degree of lymphocyte activation was assessed by measurements of the cellular uptake of [3H]thymidine and expressed in counts per minute (CPM). The suppressor lymphocyte function was estimated by a quotient between the maximum CPM values from cultures with and without preincubation. For the hyperthyroid group (n = 15) the quotient was 1.00 +/- 0.07 (mean +/- SEM), for the euthyroid patient group (n = 21) 1.12 +/- 0.05 and for the healthy control group (n = 21) 1.37 +/- 0.08. There was a significant difference between the quotients for the control group and the hyperthyroid (P less than 0.01) as well as the euthyroid (P less than 0.05) patient group. The quotients for the two groups of patients did not differ significantly. In conclusion, the present study supports the view of a defect in suppressor T lymphocyte function in patients with Graves' disease in the hyperthyroid state and indicates that this defect can persist in the euthyroid state after treatment.

Adult↗

Haemophilus influenzae, Pneumococci, group A streptococci and Staphylococcus aureus: sensitivity of outpatient strains to commonly prescribed antibiotics.

The degree of resistance of Haemophilus influenzae, pneumococci, group A streptococci and Staphylococcus aureus to phenoxymethylpenicillin, ampicillin, doxycycline, erythromycin and chloramphenicol was investigated with the MIC-method (plate-dilution technique). Each bacterial group consisted of 100 outpatient strains. Seven strains of H. influenzae were beta-lactamase-producing. Of the 100 haemophilus strains, 58% were sensitive and the rest intermediate sensitive to erythromycin. 99% were sensitive to doxycycline and all strains were sensitive to chloramphenicol. Essentially all pneumococcal strains were sensitive to the antibiotics tested. However, a few strains demonstrated diminished sensitivity to penicillins. All group A streptococci were sensitive to ampicillin, penicillin and chloramphenicol, and 98% were sensitive to erythromycin. Approximately 1 strain out of 5 was resistant to doxycycline. 75% of S. aureus were beta-lactamase producers. Four of the S., aureus strains were resistant to erythromycin and 8 to doxycycline. The results presented indicate a better antibiotic situation than in some other countries, but suggest the need for a more extensive antibiotic sensitivity examination of isolated bacteria.

Anti-Bacterial Agents↗

The effect of antibacterial agents on the association between bacteria and leukocytes.

The effect of antibacterial agents on human lymphocyte chemotaxis, phagocytic capacity, protein synthesis and the relation between morphologic and functional changes induced by antibacterial agents was studied. A significant depression of chemotaxis measured with an agarose gel technique was detected when human leukocytes were incubated with fusidic acid and rifampicin in clinically obtainable concentrations. The newer, well absorbed tetracyclines depressed chemotaxis at high concentrations, but a less pronounced inhibition was detected with classical tetracycline. The incorporation by human neutrophils of 14C-leucine into a trichloroacid insoluble fraction was markedly depressed by the same antibiotics, and it is suggested that some antibiotics acting by inhibition of protein synthesis also affect chemotaxis of human neutrophils. Doxycycline, but not lymecycline, initially decreased granulocyte adherence to glass surfaces. After 20 min of incubation granulocytes treated with both doxycycline and lymecycline adhered in higher numbers than control cells. Human leukocytes incubated with tetracycline hydrochloride or doxycycline in vitro showed a decreased capacity to phagocytize yeast and bacteria. Furthermore, leukocytes harvested from healthy volunteers after ingestion of tetracycline also demonstrated decreased phagocytic capacity. Scanning electron micrographic studies showed changed surface morphology for granulocytes incubated with tetracyclines, which might explain the changed adherence and phagocytosis by tetracycline-treated cells.

Anti-Bacterial Agents↗

Single dose doxycycline prophylaxis and peroperative bacteriological culture in elective colorectal surgery.

A prospective study was performed on 196 consecutive patients undergoing elective colonic surgery to evaluate the prophylactic effect of a single dose of doxycycline. The patients were randomized into four groups: group I 200 mg i.v. preoperatively, group III 600 mg i.v. preoperatively, group III 600 mg i.v. postoperatively, and group IV 200 mg i.v. preoperatively and 200 mg i.v. daily 3 days postoperatively. The rate of septic complications for the different groups were: I 13 per cent, II 7 per cent, III 20 per cent, and IV 19 per cent. There was no statistically significant difference in occurrence of septic complications between the groups. The degree of bacterial contamination during operation was estimated by culture from wound irrigation fluid and from cotton swabs. Bacteria were recovered from the irrigation fluid in 97 per cent, while culture from cotton swabs proved to be much less sensitive. A high number of bacteria in the irrigation fluid was significantly correlated to a high complication rate. It is suggested that direct plating from irrigation fluid can be used for defining a high risk group of patients in colonic surgery.

Aged↗

Comparative in vitro activity of first, second and third generation cephalosporins.

Minimum inhibitory concentrations (MIC) were determined against 662 recent clinical isolates for eight cephalosporins representing first, second and third generation compounds. All four third-generation cephalosporins tested (cefoperaxone, cefotaxime, ceftazidime and moxalactam) were significantly more active against aerobic gram-negative bacteria than the older compounds (cephalothin, cefamandole, cefoxitin, and cefuroxime). Cefotaxime and moxalactam were most active against Enterobacteriaceae with extremely low MIC-values. Ceftazidime was definitely most active against Pseudomonas aeruginosa with more than 90% of strains inhibited at 4 micro g/ml. MIC-values for cefotaxime against Staphylococcus aureus were for all strains 1-2 micro g/ml, slightly higher for cefoperazone, while the effect of ceftazidime and moxalactam was more limited. All third generation cephalosporins demonstrated efficiency against Streptococcus pyogenes, cefotaxime being most active and moxalactam least active, but were essentially ineffective against Streptococcus faecalis. Moxalactam demonstrated higher activity against Bacteroides fragilis than other second and third generation cephalosporins including cefoxitin. Previous studies have demonstrated a very high activity of all third generation cephalosporins against Haemophilus influenzae and Neisseria gonorrhoeae, including beta-lactamase producing strains.

Bacteria↗

Incidence of Legionella pneumophila in acute lower respiratory tract infections.

The etiological role of Legionella pneumophila and other infectious agents in acute lower respiratory tract infections in 112 patients attending an infectious disease clinic was estimated by a serological study of paired sera and bacteriological culture of nasopharynx swabs and culture and immunoelectroosmophoresis of expectorates. Only 2 of the patients had a 4-fold rise in antibody titre to L. pneumophila, suggesting a similar incidence of legionnaires' disease as reported from USA.

Adolescent↗

Several factors influencing the colonization of group B streptococci--rectum probably the main reservoir.

Women (1 268) attending a gynaecological clinic or a venereal disease clinic had positive cultures of group B streptococci from urethra in 27.8% and from rectum in 29.4%. The colonization rate was highest in patients from the venereal disease clinic (p less than 0.001). In a study of 405 of the females at different parts of the menstrual cycle group B streptococci were detected during the last half of the cycle in specimens from cervix in 18%, from urethra in 29% (p less than 0.005), and from rectum in 35% (p less than 0.001). The correlation between contraceptive methods and isolation of group B streptococci was investigated for 435 women. Females with intrauterine devices but not those using oral contraceptives had a significantly increased colonization rate genitally. The colonization rate of group B streptococci was also studied in 271 women using sanitary tampons and 129 women using sanitary towel. Those using tampons were significantly more often colonized. Cultures for Neisseria gonorrhoeae were performed from 380 patients but no correlation between N. gonorrhoeae and group B streptococci was found. The study supports the view that rectum and not the genito-urinary tract is the main reservoir of group B streptococci in females, that genital colonization mainly represents contamination from the gastrointestinal flora and sexual transmission is only one of many factors influencing the colonization rate.

Adult↗

Formalin-treated bacteria as selective B cell mitogens: results in primary and acquired immunodeficiencies.

The mitogenic activity of the formalin-treated bacterial strains Branhamella catarrhalis, Haemophilus influenzae and the Cowan I strain of Staphylococcus aureus was assessed in peripheral blood lymphocytes (PBL) from patients with primary immunodeficiencies, acute lymphocytic leukaemia (ALL), chronic lymphocytic leukemia (CLL) and in umbilical cord blood lymphocytes. The bacteria selectively stimulated B cells, as demonstrated by the finding of a normal de novo DNA synthesis in children with a T cell defect and of an absent response in X-linked agammaglobulinaemia and severe combined immunodeficiency. A decreased mitogenic activity was exerted on PBL from four out of seven adults with common variable hypogammaglobulinemia (CVH). In B-CLL the mitogenic activity was normal while in T-ALL it was decreased. Umbilical cord blood lymphocytes responded better than PBL from adults. The selective stimulative ability of the bacteria for B lymphocytes is expressed when PBL are cultured together with the formalin-treated bacteria for 48 to 72 hr.

Adolescent↗

Effect of rifampin on the immune response in mice.

In an investigation of the effect of rifampin on the immune response in mice, the cellular immunity was evaluated with the split-heart allograft technique. The survival time of the heart in animals treated with rifampin at a dose of 20 mg/kg per day from the day of the transplantation until the graft was rejected was longer (33.7 days, P less than 0.001) than that of animals not treated with antibiotics (14.5 days). When rifampin was given at a dose of 5 mg/kg per day for the same period, the mean survival time of allografts was 19.5 days. The number of demonstrable plaques of hemolysis and the humoral antibodies to sheep erythrocytes were also reduced by a human therapeutic dose (20 mg/kg per day). However, the suppression of the humoral immune response was probably of more limited biological significane, suggesting a differential sensitivity to rifampin. In contrast to rifampin, benzylpenicillin had no noteworthy inhibiting effect on the cellular or humoral immune response.

Agglutinins↗

Effect of fusidic acid on the immune response in mice.

The effect of fusidic acid on the immune response in mice was studied. At the nontoxic dose of 500 mg/kg per day, the cell-mediated immunity was strongly inhibited. A marked and significant prolonged survival of split-heart allografts in treated animals was detected. The survival time of allografts in mice receiving fusidic acid from the day of the transplantation until the grafts were rejected was 26.1 days compared with 14.5 days in untreated animals. In mice treated also before the transplantation, the mean survival of the allografts were even longer. The phytohemagglutinin response, as well as the mixed lymphocyte culture stimulation of spleen lymphocytes from mice given 500 mg of fusidic acid per kg daily for 1 week, were significantly inhibited. At the same dose there was also a significantly decreased primary antibody response to sheep erythrocytes, but it was of limited biological significance. The immunosuppressive effect in animals treated with a human therapeutic dose of fusidic acid (25 mg/kg per day) was less pronounced but significant. The relevance of these results is discussed.

Animals↗

Effects of antithyroid drugs on lymphocyte function in vitro.

The in vitro influence of 6-propylthiouracil (PTU) and methimazole (MMi) on mitogenic activation of human peripheral blood lymphocytes was studied in order to assess whether antithyroid drugs may have an immunomodulatory capacity. Lymphocytes were cultured for 72 h in the presence of phytohaemagglutinin (PHA; 1.25 microgram/ml), concanavalin A (Con A; 5.0 microgram/ml), or pokeweed mitogen (PWM; 2.5 microgram/ml). Antithyroid drugs were added to yield final concentrations of 1-1000 mu mol/liter. High pressure liquid chromatographic analyses verified that the expected drug concentrations in the incubation media were reached and maintained throughout the incubation period. The degree of lymphocyte activation was assessed by measurements of the cellular uptake of [3H]thymidine added after 48 h. PTU (at 1000 mu mol/liter) slightly suppressed PHA- and Con A-induced activation of lymphocytes but enhanced (at 5-500 mu mol/liter) PWM-induced activation. MMI (500-1000 mu mol/liter) enhanced not only PWM-induced activation but (at 1000 mu mol/liter) also enhanced PHA- and Con A-induced activation. Thus, PTU and MMI might interfere with mitogenic activation of lymphocytes. However, the effects were mainly recorded at drug concentrations exceeding those found in blood samples of patients treated with conventional doses.

Concanavalin A↗

Bacteria-immunoglobulin-lymphocyte interactions--new aspects.

Of 30 bacterial species tested 18 stimulated DNA synthesis in human blood lymphocytes. The maximum response was after 3-4 days of culture suggesting a mitogenic effect. This was confirmed by the induction of polyclonal antibody production shown by a plaque assay. Most bacterial species increased the DNA synthesis in B-enriched lymphocytes and unseparated lymphocytes but had negligible activity on T-enriched lymphocytes. Among bacteria with a mitogenic effect and ability to induce polyclonal antibody production are Staphylococcus aureus, Haemophilus influenzae, Mycobacterium tuberculosis, Neisseria gonorrhoeae, Streptococcus group A and Streptococcus pneumoniae. In an attempt to define structure (s) on the B-lymphocyte surface responsible for the lymphocyte stimulation the binding of IgD, IgM, and HLA-A, -B and HLA-D antigens to different bacterial species was investigated. A high IgD binding to N. catarrhalis and H. influenzae and a moderate binding of IgD to streptococci was found. Binding studies employing radiolabelled IgD Fab- and Fc-fragments indicated that the binding probably involves the CHl-region of the IgD molecule. Three purified radiolabelled myeloma IgM M-components were all shown to be efficiently bound to many bacteria indicating that a part of the IgM molecule other than the antigen-combining site can be involved in attachment to bacteria. Highly purified detergent-solubilized HLA-A, -B and HLA-D antigens, when separately incorporated into liposomes, were bound efficiently to two strains of N. catarrhalis and to one strain of H. influenzae weakly to one strain of E. coli, but not at all to another strain E. coli. Preliminary experiments indicate that these bacteria-immunoglobulin and bacteria-HLA-antigen interactions lead to lymphocyte stimulation.

Bacteria↗