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Biomedical subjects

S Ahlstedt

Publications and source records attributed to S Ahlstedt.

At least 145 records · Page 8Linked to original sources

Boosterable IgE antibody response in mice without the use of adjuvant.

A mouse model is presented giving boosterable IgE antibody responses preceding the IgG antibody responses without using adjuvants. Groups of CBA mice were injected subcutaneously with minute doses of penicilloyl bovine gammaglobulin, 3.8-94 ng daily for one or two 10-day periods. Some groups of animals were simultaneously given Bordetella pertussis bacteria intraperitoneally. The IgE antibody responses were recorded with passive cutaneous anaphylaxis (PCA) in rats as well with RAST. IgG antibody responses were determined with a double antibody assay. An overall good agreement between the antibody activity in the PCA and RAST was seen, both tests showing boosterable IgE antibody responses. Some discrepancies between the two tests are discussed.

Adjuvants, Immunologic↗

Antibody responses to impurities of penicillin in infants and rabbits.

Antibody responses to penicilloyl were recorded in infants and children treated for about 1 week with intravenous ampicillin. In this single-blind, randomized study two commercially available preparations were compared, one of high-grade purity (less than 0.1 microgram antigen per gram) and the other slightly contaminated with high molecular weight proteinaceous material (1.5 microgram antigen per gram) according to a radioimmunoassay. The results showed no significant increase in the antibody titers in any of the patient groups. The immunogenic properties of high molecular weight proteinaceous impurities isolated from phenoxymethyl penicillin during manufacture were tested in rabbits given daily subcutaneous injections with 0.1-10 micrograms of the antigen over 10 day periods. When the 10-day period was repeated, the rabbits injected with more than 2 micrograms of antigen responded with both IgM/IgG and IgE antibodies. The clinical as well as the animal study indicates that antigen impurities in the preparations of the order of 2 micrograms per gram or less do not elicit a significant antibody response. However, the study in rabbits demonstrates that high molecular weight impurities can induce penicillin allergy if present in about 10-fold higher quantities than those usually found in the commercial penicillin preparations of today.

Ampicillin↗

Dextran-reactive antibodies in healthy infants and toddlers--relation to type of feeding.

The appearance of dextran-reactive antibodies (DRA) during the first 2 years of life was studied in 88 healthy newborn babies in an effort to provide information about the origin of DRA in normal persons. The results were related to type of feeding, immunizations and to blood group of infants and their mothers. No DRA were detected in cord sera by passive hemagglutination. At 3 months of age 42% had DRA, at 8 months 95% and at 27 months 84%. The latter figure corresponds to previous reports of DRA in healthy adults. Peak titers were also seen at 8 months (mean 2 log titers at 3, 8 and 27 months; 2.1, 6.2 and 4.9, respectively). Breast-feeding influenced the time of appearance of DRA and the magnitude of the titers. Babies breast-fed at 3 months more often were DRA negative than those that had received cow's milk-based formula at that time (p less than 0.005). However, in those breast-fed babies that were DRA positive the titers were higher than in the formula-fed infants (p less than 0.001). Other types of feeding e.g. juices did not influence the DRA levels. The appearance of DRA could not be explained by polyclonal stimulation of antibody production since changes of DRA titers in 11 tested patients could not be clearly related to similar changes of levels of antibodies to an unrelated hapten, trinitrophenyl. The study demonstrates that DRA appear during the first year of life, and that the appearance is influenced by exogenous factors. The most likely source of the antigen stimulation is the gastrointestinal flora which is altered by introduction of cow's milk into the diet.

Age Factors↗

Contact sensitivity in guinea pigs to different penicillins.

The ability of penicillins of varying lipophilicity to induce and elicit cellular allergic responses were analysed in guinea pigs. Epicutaneous application of the penicillins benzylpenicillin (Bp), cloxacillin (Clox) and Bacampicillin (Bamp) did not cause any unspecific skin irritation. Intracutaneously injected, however, Bamp, Clox and to a lesser extent Bp caused irritation at concentrations of 1.25%. Solutions of 0.12% of penicillins were inactive in this respect. Cellular allergic responses were induced with Bp, Bamp and Clox after repeated epicutaneous application. The magnitude of responses was related to the lipophilic properties of the penicillins, Bamp being superior. In the guinea pig maximization (GPM) test of Magnusson and Kligman employing intradermal injections of the penicillins with Freund's complete adjuvant, similar sensitizing abilities of the three penicillins were observed. The cellular allergic responses were elicited with Bp, Bamp, Clox and in addition ampicillin and the 1'-ethoxycarbonyloxyethyl ester of Bp. An extensive cross-reactivity between the penicillins was seen in Bp- and Bamp-sensitized animals, whereas the Clox-sensitized animals showed a specificity limited to Clox. Bamp was shown to possess a superior activity to elicit reactions, possibly due to its lipophilic properties together with an irritating effect exerted by the NH2 group.

Ampicillin↗

Mice do not respond with delayed hypersensitivity to penicillin-derived determinants.

Penicillin structures of varying lipophilicity were used to induce delayed hypersensitivity (DH) in different strains of mice. Epicutaneous application on inflamed skin or intracutaneous or subcutaneous injection with Freund's complete adjuvant did not induce DH, despite the fact that picrylchloride readily produced such responses. Sheep, rabbit and mouse red cells as well as mouse lymph node and epidermal cells conjugated with various amounts of penicillin injected subcutaneously in the base of the tail did not induce a DH reaction to penicillin either, whereas such responses to other cellular components and also to the TNP determinant after using picryl sulphonic acid conjugated spleen cells were recorded. Since the mice in other studies have been shown to respond with antibodies to soluble penicilloyl protein conjugates, but never to penicillin itself, we concluded that this species of animal is incapable of responding to penicillin with DH.

Animals↗

Dimeric IgA in the rat is transferred from serum into bile but not into milk.

Intravenous administration of ductus thoracicus lymph with dimeric IgA antibodies against Escherichia coli 06 to lactating rat dams did not result in transfer of IgA antibodies into the milk, although the antibodies were detectable in serum 1 min after the administration and in bile 60 min later. After intravenous injection of serum from bile-duct-occluded (BDO) rats immunized in the Peyer's patches into lactating rat dams. IgA antibodies appeared in the serum and remained there up to 230 min. At this time no IgA antibodies were seen in the milk while they were present in bile. IgG and IgM 06 antibodies did not appear in bile or milk after intravenous administration of lymph or serum from BDO rats.

Animals↗

Hapten and kidney antibodies in serum from children with urinary tract infection.

The presence of antibodies against the synthetic hapten dinitrophenol (DNP) was investigated in sera from healthy children and adults. Such antibodies were found in all sera. The serum levels were significantly lower in healthy children than in adults. Serum samples from a pilot group of pediatric patients with acute E. coli urinary tract infection (UTI) contained significantly higher DNP antibody levels compared to healthy children and similar to those of the adults. Furthermore, 10 of 17 patients had a significant change in antibody levels in connection with the infection as judged from consecutive serum samples. Relations were found between age and minimum as well as maximum serum DNP antibody values. In a second group of children with E coli urinary tract infection beside DNP antibodies, antibodies against the Tamm-Horsfall urinary protein and a pool of O antigens from E. coli common in urinary tract infections were also investigated. In these patients similar findings as for the pilot group were made for the levels of the DNP antibodies. An IgG but not IgM antibody response to the Tamm-Horsfall protein was also found in sera from all the patients over 1 year with acute pyelonephritis. The highest antibody levels against Tamm-Horsfall protein were noted in patients with vesico-ureteric reflux. No relation could be recorded between the DNP antibodies and the Tamm-Horsfall protein antibodies. The antibodies to the pool of O antigens recorded did not correlate to the DNP antibodies. It was concluded that the DNP antibody formation could partly be due to polyclonally stimulatory activities of bacterial substances exposed during infections.

Adult↗

Joint inflammation in rabbits induced by preformed immune complexes.

The rabbit knee joint was used to evaluate the inflammatory properties of immune complexes with different contents of antigen. Immune complexes made in vitro with antiserum from hyperimmunized rabbits and bovine serum albumin as antigen were injected into the joints. The reactivity of the individual animal was established by injection of normal rabbit serum into the contralateral joint. The number of leukocytes washed out from the joints at fixed intervals was used as a measure of the inflammatory properties of the immune complexes. With immune complexes formed at antigen excess the highest numbers of leukocytes, with a predominance of granulocytes, were found after 6 h of exposure. However, these complexes gave only weak complement activation in vitro, measured with a hemolysis assay. Complexes formed at optimal precipitation proportions gave high complement activation in vitro but only a small number of leukocytes in the joints at 6 h exposure. This finding may be explained by a rapid phagocytosis of the latter complexes while complexes formed at antigen excess are not readily phagocytized. This hypothesis is supported by the observation that higher leukocyte counts were found after shorter exposure times to complexes formed at optimal precipitation proportions than after exposure to complexes with antigen excess.

Animals↗

Evaluation of circulating immune complex-like material for development of skin reactions in connection with penicillin therapy.

The levels of immune complex-like material in serum from 18 patients in connection with skin eruptions appearing during penicillin therapy were determined with a modified ELISA. Immune complex-like material could only be shown in the serum of 3 out of the 17 patients. However, according to ELISA results, the complexes appeared without the simultaneous presence of penicilloyl-specific antibodies. Neither could penicilloyl-specific antibodies be recorded in 9 patient treated with parenteral penicillin without adverse reactions. 3 of these patients had immune complex-like material in their serum. It was concluded that immune complex-like material with penicilloyl specificity is not likely to contribute to the development of skin eruptions often seen in connection with penicillin treatment.

Adolescent↗

Protective effect of sublethal intraperitoneal Listeria infection secondary to intranasal influenza infection in aged immunodeficient mice.

Aged mice of the CBA/Ca strain, 15 months of age, and A/J mice, 17 months of age, exhibited impaired lymphoblastogenic response to concanavalin A but not to lipopolysaccharide. This defective cellular responsiveness was not accompanied by decreased antibody response to protein antigen or decreased ability to develop delayed hypersensitivity to picryl chloride. An increased susceptibility to influenza virus infection given intranasally was noted in the aged mice as compared with young animals. Such virus infection also impaired the lymphoblastogenic response to mitogens. Surprisingly, the virus infection in aged animals was less lethal after a subsequent infection with a small inoculum of Listeria bacteria.

Administration, Intranasal↗

Antibody responses in man after single or repeated treatment with intramuscular ampicillin.

Antibody responses to the penicilloyl moiety were recorded in patients treated intramuscularly with ampicillin for respiratory infections. For practical reasons this was performed at two clinics. At each clinic, two commercially available ampicillin preparations were used in a single-blind, randomised study. One of the preparations at each clinic was of high-grade purity and the other was slightly contaminated, according to a radioimmunoassay. There was the same heterogeneity in the patient material between the two clinics. The results showed a slight but significant (p less than 0.001) increase in IgM penicilloyl antibodies in the group of patients treated with the pure penicillin but not in those treated with the contaminated penicillin. When the patients in the two studies were analysed jointly, the increase in IgM antibodies was significantly greater (p less than 0.05) in the group treated with pure penicillin than in that treated with impure penicillin. The difference in antibody formation between the patient groups treated with pure or contamined ampicillin at each clinic was not significant, however. An immunological activity of the impurities suppressing the IgM antibody response is suggested.

Adult↗

Experimental Escherichia coli 06 infection in mice. III. Effects of malnutrition, immunization and nutritional restoration.

Inbred mice of the CBA and A strains were from weaning malnourished on a low protein diet. During a three-week period their weight increased from about 8 to about 10 g, while mice on normal feeding increased to about 16 g. This malnutrition resulted in a 10-fold increase of the susceptibility to intraperitoneally injected E. coli 06:K2a,2c:H1 bacteria compared to conventionally fed controls. Immunization as well as transfer of fresh immune serum to malnourished or normally-fed mice resulted in an increase in resistance, 6 to 10 fold that of non-immunized controls, while transfer of normal serum did not have a great impact on the resistance. Antibody titers to El coli 06 antigen in mice on poor and normal feeding were similar, as were there non-specific cellular responsiveness measured as lymphoblast transformation by ConA, PHA and LPS. The effect of the malnutrition seemed to be an impairment of the clearance of live E. coli 06 bacteria 1 h after a sub-lethal infection compared with that of normally-fed controls. The noted increased susceptibility to injections in the malnourished mice was rapidly restored by normal feeding for one day.

Animal Feed↗

Experimental Escherichia coli 06 infection in mice. IV. On the relative importance of complement factors and antibodies for the host defence.

Treatment of CBA mice with cobra venom factor (CVF) decreased their C3 levels to less than 10 per cent of normal and resulted in a simultaneous increase of their susceptibility to intraperitoneal E. coli 06 infection. Animals immunized and treated with CVF had an infection resistance similar to untreated controls but considerably less than mice immunized only. The CVF treatment did not affect the antibody formation after immunization. Untreated or immunized AKR mice deficient in C5 did not show decreased resistance to the infection. Exposure of NMRI mice to preformed antigen-antibody complexes unrelated to the infection did not increase the susceptibility of the animals to infection, neither did it impair their C3 levels. Two out of five freshly frozen (-70 degrees C) normal rabbit sera gave significant, heat-labile protection of mice to the E. coli infection without containing any antibodies detectable with the ELISA. This protective capacity was not abolished with zymosan treatment affecting the levels of complement factors and could be "natural antibodies" stimulated from the environment. In testing whether similar protective factors as those found in normal rabbit serum could be raised in CBA mice, such animals were orally given killed E. coli 06 bacteria. This did not affect the resistance to the E. coli infection or to the rise of specific antibodies after immunization.

Animals↗