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Biomedical subjects

B Carlsson

Publications and source records attributed to B Carlsson.

At least 181 records · Page 10Linked to original sources

A survey on the reduction of animal use in projects funded by the National Board for Laboratory Animals (CFN) 1979-1987.

A survey was carried out on the reduction of animal use in the projects funded by the CFN between 1979 and 1987. 63 projects had received funds. 37 projects were reported in time for the symposium, and the results were presented there; surveys on another 11 projects were received later. The projects funded covered different areas, basic research, testing, evaluation studies, biological production, vaccine testing, education, improved animal experimental techniques, therapy and problems with in vitro toxicology. They were all in line with the objective of the CFN, which is to reduce animal experimentation in Sweden. A definite reduction in animal use is reported in some studies and predicted to take place as a result of others, either relatively soon or in a longer perspective. The survey has a bias, since the scientists themselves were asked to report on their projects and evaluate the effects of the reduction in the use of animals. However, the answers give rise to new interesting questions about future possibilities of animal reduction in a variety of areas and this points at one of the main conclusions, namely the need for further investigation into areas of interest. In order to work out a realistic strategy for reduction of animal use, a coordinating body is needed to investigate areas of promise, where animals either can be reduced or experimental techniques refined, and develop strategies for addressing target areas. The CFN should play such an offensive role.

Animal Testing Alternatives↗

Antibody-mediated immunity in the neonate.

Our knowledge about the protective value of the passive immunity provided by maternal IgG via placenta and SIgA via the milk is still incomplete. Although more detailed information is required it is clear that both forms of passive protection are important for the neonate. The immune response of neonates in secretions appears earlier and is more efficient than previously realized, providing SIgA as well as IgM in e. g. saliva. The presence of anti-antibodies (anti-idiotypes) in the transplacental IgG and milk SIgA may in fact actively prime the immune system of the fetus and the breast-fed infant. This could be one explanation why breast-fed infants seem to respond better to ordinary parenteral and peroral vaccines, in secretions as well as in serum than those fed a high or low protein formula.

Humans↗

Estrus cycle-dependent co-variation of insulin-like growth factor-I (IGF-I) messenger ribonucleic acid and protein in the rat ovary.

It has been suggested that insulin-like growth factor-I (IGF-I) exerts paracrine or autocrine actions in the ovary and may play a role in the regulation of ovarian function. We have examined ovarian levels of IGF-I mRNA and IGF-I protein throughout the estrus cycle. The lowest levels of IGF-I mRNA were found on proestrus (12.00 h). The mRNA levels on estrus (12.00 h) were significantly (P less than 0.05) higher than on proestrus. The correlation between the levels of IGF-I and IGF-I mRNA was linear and significant (r = 0.706; P less than 0.01). Our observations that the IGF-I gene expression and translation vary during the estrus cycle, with an increase between proestrus and estrus, suggest that the gonadotropin surge could be of importance for the regulation of IGF-I in vivo and that IGF-I may be involved in the cell proliferation and differentiation caused by these hormones.

Animals↗

Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities.

HLA class II gene polymorphism was investigated in 100 patients with clinically definite multiple sclerosis (MS) by restriction fragment length polymorphism analysis of Taq I-digested DNA using DRB, DQA, and DQB cDNA probes. Twenty-six patients had primarily chronic progressive MS and 74 had relapsing/remitting MS. The latter group included patients with a secondary progressive evolution of symptoms. Both clinical forms of MS were found to be associated with the DRw15,DQw6 haplotype. In addition, primarily chronic progressive MS was positively associated with the DQB1 restriction fragment pattern seen in DR4,DQw8, DR7,DQw9, and DRw8, DQw4 haplotypes, as well as negatively associated with the Taq I DQB1 allelic pattern corresponding to the serological specificity DQw7. Relapsing/remitting MS was positively associated with the DQB1 allelic pattern observed in the DRw17,DQw2 haplotype. These three DQB1 alleles are in strong negative linkage disequilibria with DRw15. The two susceptibility markers of each clinical form of MS act additively in determining the genetic susceptibility, as the relative risks for individuals carrying both markers roughly equal the sum of respective risks. Different alleles of the DQB1 locus defined by restriction fragment length polymorphisms contribute to susceptibility and resistance to primarily chronic progressive MS as well as to susceptibility to relapsing/remitting MS. The observed immunogenetic heterogeneity between the different clinical forms of MS favors the hypothesis that primarily chronic progressive MS and relapsing/remitting MS are two distinct disease entities.

Alleles↗

Specificity of HLA restricting elements for human nickel reactive T cell clones.

In order to study the fine specificity of HLA class II restriction, we have established nickel specific T cell clones from a nickel allergic patient. Cells were cloned by limiting dilution after primary stimulation and selection of nickel specific blasts. Several clones were established which were all shown to carry the CD4 marker. All clones were shown to be completely blocked by monoclonal antibodies directed against DR antigens, but unaffected by antibodies against DQ or DP, thus demonstrating their DR specificity. For the study of HLA class II restriction, a panel of cell donors was carefully HLA typed by including the use of DRB and DQB cDNA probes. Specificity analysis, using allogeneic antigen presenting cells, revealed that the clones were either restricted to DR3- or DR4-like molecules, which is consistent with the fact that the donor was DR3, DR4 positive. However, the studies also revealed that the fine specificity of the DR3 and DR4 restriction could not be completely assessed by serological and genomic typing of panel cells. This indicates that cellularly defined HLA restriction elements recognized by T cells cannot be defined properly with available class II typing methods, and the results of these experiments documented the additional polymorphism of class II restriction elements. The clonal specificity analysis has shed further light on the biologically relevant level of DR polymorphism.

Clone Cells↗

Individuals with HLA-DR blank alleles display well-known DR-DQ RFLPs.

We have characterized HLA-DRB, -DQA, and -DQB gene polymorphism in a large number of serologically DR blank haplotypes with the restriction enzymes Taq I, Bam HI, and Pvu II, with the aim of finding new RFLPs in the Caucasian population. Locus-specific RFLPs were combined for a definition of Taq I DR-DQ haplotypes. All observed DNA haplotypes could be found in a control group of 100 individuals, but with a different distribution. Serologically less well-defined specificities were over-represented in the blank group, in particular the DRw13-associated Taq I DR-DQ haplotype T-13.3. We conclude that the majority of DR blank haplotypes are probably closely related or identical to previously defined DR alleles. The extent of DR polymorphism in the Caucasian population seems to be well mapped, considering the extremely small proportion of rare Taq I DR-DQ haplotypes and lack of new patterns in this study.

Alleles↗

Plasma growth hormone pattern regulates epidermal growth factor (EGF) receptor messenger ribonucleic acid levels and EGF binding in the rat liver.

It has recently been shown that GH increases the number of available hepatic receptors for epidermal growth factor (EGF). In the present study the effects of the sexually dimorphic plasma GH pattern (higher pulsatility in male rats) on hepatic EGF binding and EGF receptor mRNA concentration were investigated. The specific binding of [125I]EGF to purified liver membranes was about 2-fold higher in male rats than in females on days 35, 50, and 80 of life. EGF receptor mRNA levels, as determined by an RNase protection solution hybridization assay, were higher in males only on days 47-50. Hypophysectomy on day 50 reduced the EGF receptor mRNA concentration to a level that did not differ between male and female rats. In hypophysectomized rats of both sexes, intermittent GH treatment (sc injections every 12 h for 7 days) enhanced hepatic EGF receptor mRNA concentrations to normal male levels, while continuous GH administration was less effective. Northern blot analysis indicated that transcripts with apparent sizes of 9.5 and 6.6 kilobases were dependent on the plasma GH pattern. Intermittent iv GH replacement therapy for 5 days given at 3-h intervals by an automatic iv infusion system increased the hepatic EGF receptor mRNA concentration as well as specific EGF binding, whereas continuous iv GH infusion was ineffective. These results show that a pulsatile plasma GH pattern, similar to that of male rodents, is markedly more effective in enhancing hepatic EGF receptor mRNA levels and EGF binding than a continuous feminine GH pattern. These results are consistent with a pretranslatory stimulation of EGF receptor synthesis by pulsatile GH.

Animals↗

The influence on the secretory IgA antibody levels in lactating women of oral typhoid and parenteral cholera vaccines given alone or in combination.

41 lactating Pakistani women were vaccinated orally with Salmonella typhi vaccine alone or in combination with parenteral Vibrio cholerae whole cell vaccine, in order to study the possible difference in the secretory response after live and inactivated vaccines. The antibody response in saliva, milk and serum was recorded using the enzyme-linked immunosorbent assay, ELISA. All had prevaccination antibody levels against the 2 vaccines. The live S. typhi vaccine gave a serum IgG and IgA response but did not influence the IgM levels. Salivary or milk secretory IgA (SIgA) antibody levels showed both increases and decreases but in most cases remained unchanged. Even if the vaccine was given in enteric coated capsules, the milk and salivary SIgA response was more often decreased than increased, although somewhat higher serum IgG levels were attained with this preparation. Parenteral cholera vaccination enhanced both serum and SIgA milk antibody response. Combination of the 2 vaccines did not have any untoward effect on the antibody response in serum or in secretions against V. cholerae or S. typhi LPS. The results show that an oral vaccine often induces a rather poor, or even negative mucosal antibody response, while a parenteral vaccine provokes a substantial SIgA response in individuals orally primed by natural exposure. This is in agreement with our previous findings with oral and parenteral poliovirus vaccines in this population.

Administration, Oral↗

A DR4-associated DR-DQ haplotype is significantly associated with rheumatoid arthritis.

Forty-three patients with seropositive, erosive rheumatoid arthritis (RA) and 24 members of 5 RA multicase families were studied for HLA class II gene polymorphism, using restriction fragment analysis with complementary DNA probes for DR beta and DQ beta chains. This method generates HLA-DR-DQ haplotypes that are highly correlated with HLA-DR serology. Thirty-five of the 43 RA patients (81%) were positive for one or for both of the DR4-associated DR-DQ haplotypes, 4.1 and 4.2. Among these patients, the 4.1 haplotype was found significantly more often than in DR4+ controls (P less than 0.01). The haplotype segment C3;B15;DR4 was present in all RA patients in 4 of the 5 families, and included the DR-DQ4.1 haplotype.

Adult↗

Inadequacy of mucosal IgM antibodies in selective IgA deficiency: excretion of attenuated polio viruses is prolonged.

A nationwide vaccination campaign with oral poliovirus vaccine was organized in Finland in 1985 in order to cease an outbreak of poliomyelitis. We followed eight IgA-deficient individuals and nine controls for poliovirus excretion in feces and for antibody responses in serum and saliva. Five weeks after oral poliovirus vaccination all eight IgA-deficient individuals were still excreting polioviruses, in contrast to one of nine controls. The concentration of polioviruses, as estimated by a semi-quantitative immunofluorescent assay, was generally higher and the test was significantly more often positive in the samples from the IgA-deficient individuals. Although serum levels of antibodies to poliovirus type 3 were lower in IgA-deficient individuals before vaccination, both measurements showed that the two groups had similar antibody levels 4 weeks after vaccination. IgA-deficient individuals lacked salivary IgA antibodies to poliovirus types 1 and 3 but had increased levels of IgM antipolio antibodies, which were shown to carry secretory component. We conclude that the mucosal IgM antibodies of IgA-deficient individuals eliminate polioviruses less efficiently than do the IgA antibodies of normal individuals.

Adolescent↗

Vasoactive intestinal peptide stimulates oocyte maturation, steroidogenesis, and cyclic adenosine 3',5'-monophosphate production in isolated preovulatory rat follicles.

Vasoactive intestinal peptide (VIP) is present in the rat ovary and has been shown to stimulate cyclic adenosine 3',5'-monophosphate (cAMP) and progesterone production in cultured rat granulosa cells. In the present study, VIP-stimulated cAMP production has been studied in relation to steroid accumulation and oocyte maturation in isolated preovulatory rat follicles. VIP stimulated resumption of meiosis (oocyte maturation) in up to 60% of the follicle-enclosed oocytes after 6 h at 1 microM (control, 1.8%; luteinizing hormone 99%). The effect was time- and dose-dependent up to 6 h and was seen with both natural and synthetic VIP. VIP also stimulated the accumulation of steroids (estrogen, 2.3-fold; testosterone, 2.0-fold; and progesterone, 1.6-fold increase after 6 h of incubation) and lactate (2.6-fold) by the follicles. VIP-increased tissue levels of cAMP in the follicle were dose- and time-dependent. This effect was potentiated by a phosphodiesterase inhibitor. When isolated oocyte-cumulus complexes were studied, VIP caused a transient inhibition of spontaneous oocyte maturation, and demonstrated no effect on denuded oocytes. These results extend earlier preliminary observations on the ability of VIP to induce meiotic maturation of follicle-enclosed oocytes. Our results also show that VIP can stimulate steroid and lactate accumulation in the isolated follicles. The pattern of steroids produced suggests an effect both on the theca- and granulosa cells. We also show that VIP can delay spontaneous oocyte maturation. These effects appeared, at least partially, to be mediated by cAMP.

Animals↗