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O Vainio

Publications and source records attributed to O Vainio.

At least 91 records · Page 5Linked to original sources

Ontogeny of alloreactivity in the chicken as measured by mixed lymphocyte reaction.

Ontogeny of alloreactivity in the chicken thymus and spleen was studied in mixed lymphocyte cultures. Mixed lymphocyte reaction (MLR) to total major histocompatibility complex (MHC) (B-complex in chicken) disparity was first detected in the thymus of 16-day-old embryo and regularly detectable from the 18th embryonal day on. Small strain-specific differences in the strength and appearance of the response were, however, observed. MLR to class I MHC (B-F) antigen disparity was not detectable before hatching. Exogenous interleukin-2-containing supernatant added to the cultures had only a minor effect on MLR of embryonal thymocytes. In the spleen, MLR was first detectable in some strain combinations on day 3 and regularly found on the 7th day posthatching, indicating colonization of peripheral lymphoid organs by thymus-derived mature T cells. Our results show the association of phenotypic and functional maturation of chicken T cells. The ontogeny of alloreactivity can now be compared to the appearance of T cell receptor (TCR), CD4, and CD8-bearing cells in the thymus and peripheral lymphoid organs.

Animals↗

Single-dose pharmacokinetics of detomidine in the horse and cow.

The pharmacokinetics of detomidine, a novel analgesic sedative, was studied in the major target species after high (80 micrograms/kg) i.v. and i.m. doses. In addition, drug residues in some organs were determined. Concentrations were measured using a sensitive, detomidine-specific radio-immunoassay method. Rapid absorption following i.m. dosing occurred. Absorption half-lives were 0.15 h (horse) and 0.08 h (cattle). The mean peak concentration in the horse (51.3 ng/ml) was achieved in 0.5 h and in the cow (65.8 ng/ml) in 0.26 h. The areas under the concentration curve after i.m. dosing were 66% (horse) and 85% (cow) of the corresponding i.v. values. Distribution was rapid with half-lives of 0.15 h (horse, i.v.) and 0.24 h (cow, i.v.). The apparent volume of distribution was higher after the i.m. dosing (horse 1.56 l/kg, cow 1.89 l/kg) than after i.v. dosing (horse 0.74 l/kg, cow 0.73 l/kg). Elimination half-lives were 1.19 h (horse) and 1.32 h (cow) for the i.v. dose and 1.78 h (horse) and 2.56 h (cow) for the i.m. dose. Total clearances ranged from 6.7 (horse, i.v.) to 12.3 (cow, i.m.) ml/min/kg. Renal clearances were less than 1% of the total clearances showing negligible excretion of the drug in urine and suggesting elimination by metabolism. A cross-reacting metabolite in urine corresponded to less than 1.5% of the detomidine dose's immunoreactivity. High-dose detomidine increased urine flow significantly. Excretion of detomidine in milk in cattle was extremely low. No detectable amounts were present 23 h after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Sedative and analgesic effects of medetomidine in dogs.

The sedative and analgesic effects of medetomidine were studied in 18 laboratory beagles in a randomized cross-over study which was carried out in a double-blind fashion. Xylazine was included as a positive control and placebo as a negative control. Medetomidine was used at doses of 10, 30, 90 and 180 micrograms/kg i.m. compared to a dose of 2.2 mg/kg xylazine i.m. Parameters closely related to sedation were used to measure the degree of sedation. These were a posture variable (including evaluation of the dog's posture without external disturbance and resistance when laid recumbent) and a relaxation variable (including relaxation of the jaws, upper eyelids and anal sphincter). The first signs of sedation were recorded 1.5-3.5 min after administration of both drugs. The dogs sat down at 0.6-2.6 min post-injection and became prone at 1.9-5.9 min. Medetomidine dose-dependently affected the posture of the dogs and the relaxation variable--the higher the dose, the stronger and longer lasting the effect recorded. The sedative effect of xylazine was comparable to a medetomidine dose of 30 micrograms/kg. The analgesic effect was assessed as changes in the response to superficial pain induced by electrical stimuli. The response threshold increased significantly with both drugs and the effect of medetomidine was dose-dependent. The effects of the doses of 30 micrograms/kg medetomidine and 2.2 mg/kg xylazine did not differ significantly. In summary, medetomidine possessed an excellent sedative effect associated with analgesia in dogs.

Adrenergic alpha-Agonists↗

B-cell differentiation in the chicken: expression of immunoglobulin genes in the bursal and peripheral lymphocytes.

We have studied the expression of immunoglobulin genes in the chicken B-cell precursors, and of a B-cell surface marker (Bu-1) on the bursal and peripheral B cells during normal ontogeny. Since there is no way of distinguishing the precursor cells from the more mature bursal lymphocytes on the basis of surface markers, we chose to study the total bursal lymphocyte population at ages when the numbers of the various precursor cells (bursal, early post-bursal, and post-bursal stem cells) in the bursa are estimated to be at their highest. Thereafter, comparisons with the more mature lymphocytes in the peripheral organs were made. As a result, levels of the lambda and mu transcripts and expression of Bu-1 antigen in the chicken B-cell precursors were found to be unchanged during the post-hatching period. In the light of these experiments, the later events of B-cell differentiation, i.e. the development from the bursal to post-bursal B lymphocytes, occurs without the lambda, mu, and Bu-1 gene loci involved. On the other hand, the higher level of lambda and mu expression in the splenic B lymphocytes indicates that the post-bursal stem cells mature into highly active plasma cells after seeding to the peripheral organs.

Animals↗

B cell-induced tolerance to class II MHC antigens in the chicken.

Transplantation of cells from the bursa of Fabricius reconstitutes the B cell system of chemically bursectomized chickens. Even allogeneic bursa cells can restore the recipient's B cell system and induce tolerance to donor major histocompatibility complex antigens, but the chimeras cannot mount a T-dependent antibody response. In order to study the mechanisms of tolerance to class II MHC (B-L) antigens, we transplanted class II-incompatible bursa cells from 4-day-old donors into cyclophosphamide-treated recipients of the same age. Donor and host cells carried different allelic products of a genetically polymorphic B cell alloantigen (Bu-1), allowing us to detect cellular chimerism using monoclonal antibodies and immunofluorescence. The B cell-chimeric chickens were tested for tolerance by skin grafting, graft-versus-host splenomegaly assay, and mixed lymphocyte reaction. Specific unresponsiveness to donor MHC antigens was observed in all three tests. When spleen cells from chickens tolerant of donor class II antigens were transferred into irradiated secondary recipients of the same strain, several of the secondary recipients accepted primary donor-type skin grafts. Most secondary recipients were, however, reactive in the GVH assay and MLR. Depletion of chimeric B cells before spleen cell transfer impaired the transferability of tolerance to class II disparity. Altogether, our results indicate that tolerance to class II antigens can be induced with B cells. They suggest that at least two different mechanisms maintain the unresponsiveness in B cell-chimeric chickens.

Animals↗

Effects of medetomidine on the experimental auricular pain in dogs.

The analgesic effect of medetomidine was studied in ten laboratory beagles. The doses of medetomidine used were 10, 30 and 80 micrograms/kg BW. Xylazine (3 mg/kg BW) was included as a positive control and placebo as a negative control. The test utilized two independently randomized Latin square designs (5 x 5) and was carried out in a double blind fashion. Noxious stimuli were induced with a round pointed thermal probe which was set to produce a temperature of +44.9 +/- 0.2 degrees C. The wall of the external auditory canal was touched with the heated point of the probe. The time period from the start of the attachment to the avoidance reflex was measured and recorded as response time. To avoid tissue damage the heat treatment was stopped after 5 s even though the dog did not respond. Medetomidine clearly prolonged the response time. At the highest dose of medetomidine (80 micrograms/kg) all dogs reached the analgesic stage where they did not respond to the heat treatment. At 30 micrograms/kg of medetomidine half of the dogs had a prolonged response time. The lower dose of 10 micrograms/kg had no appreciable effect. Xylazine-induced analgesia was comparable to that of 30 micrograms/kg of medetomidine: half of the dogs lost their avoidance reflex. In conclusion, medetomidine proved to have a dose dependent analgesic effect in experimental auricular pain in dogs.

Adrenergic alpha-Agonists↗

Introduction to the clinical pharmacology of medetomidine.

Medetomidine is a sedative and analgesic drug intended for use in dogs and cats but it can also be successfully used in many other species. The effect of medetomidine is dose dependent at the recommended dose range (10-80 micrograms/kg for dogs and 50-150 micrograms/kg for cats). At doses higher than the recommended ones the strength of sedation does not increase, only the duration of the effect. From the cardiovascular changes induced with medetomidine, the profound bradycardia is most prominent. It can be transiently prevented with atropine or glycopyrrolate medication. An initial increase in arterial blood pressure followed by a longer lasting slightly hypotensive or normotensive period can be observed. Respiratory frequency tends to decrease but the changes stay within normal limits for resting animals. Vomiting may occur during the induction period of sedation. Occasional muscle jerks can be observed. Hypothermia has been reported in every animal sedated with medetomidine. Medetomidine can be used as preanaesthetic prior to ketamine, barbiturate and halothane anaesthesia.

Adrenergic alpha-Agonists↗

Cardiovascular and respiratory effects of medetomidine in dogs and influence of anticholinergics.

A total of 10 laboratory beagles was used to determine the cardiovascular and respiratory effects of medetomidine. The effects of atropine sulphate and glycopyrrolate on heart rate were also observed. Xylazine was included as a positive control. Medetomidine induced initial hypertension followed by a longer lasting hypotensive period. Evident bradycardia with second degree atrioventricular blocks and decrease in respiratory frequency was observed. Atropine sulphate and glycopyrrolate transiently abolished the bradycardic effect of medetomidine. Xylazine exhibited a similar cardiovascular and respiratory pattern to medetomidine.

Animals↗

Detomidine.

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Animals↗

Can B cells turn on virgin T cells?

The first event in the initiation of an immune response is the capture and presentation of antigen to T cells. Such presentation involves two distinct steps: (1) display of the antigen, which requires uptake, processing and re-expression of the antigen in association with MHC molecules on the presenting cell surface; and (2) triggering, in which the presenting cell provides signals leading to the activation of the responding T cell. Two sorts of cells can capture antigens, the 'professional' antigen-presenting cells (APCs) such as dendritic cells and macrophages, and the B cells. Both types of cells can display antigens and the APCs are known to be able to trigger resting T cells. But despite in vitro evidence that certain B-cell types can reactivate previously-activated T cells, it is not yet clear whether a B cell can initiate an immune response by providing the signals necessary to activate a resting T cell. We reasoned that resting B cells should not have this capacity because of the problems this would present with tolerance to self idiotypes. By exploiting the unique properties of the avian haematopoietic system, we have examined the presenting capacity of B cells in vivo and found that resting B cells are indeed unable to activate resting T cells.

Animals↗

Antigen-presenting cell-T cell interaction in the chicken is MHC class II antigen restricted.

The involvement of the MHC in the recognition of Ag by avian T lymphocytes was analyzed. PBL from chickens primed with keyhole limpet hemocyanin in vivo were induced to synthesize DNA in an in vitro response to specific Ag. Responding cells were T cells as judged by immunofluorescence staining. In vivo Ag-primed PBL were stimulated in vitro with specific Ag and further propagated in the presence of IL-2. Subsequent Ag-specific T cell proliferation required the presence of Ag-pulsed peripheral blood adherent cells (APC). T cell responses were restricted by the MHC of the APC; Ag presented by allogeneic APC did not support T cell proliferation. By using MHC-recombinant chicken lines, the gene products controlled by MHC class II loci were shown to restrict the T cell-APC interaction. This conclusion was substantiated by the inhibition of the Ag-specific T cell response by a mAb against chicken MHC class II gene products but not by a mAb against chicken MHC class I gene products.

Animals↗

Expression of B-L and Bu-1 antigens in chickens bursectomized at 60 h of incubation.

Differences in expression between B-L (chicken class II major histocompatibility complex antigen) and Bu-1 B cell antigens were found in normal animals by using monoclonal antibodies and flow cytometric immunofluorescence analysis. Fluorescence intensity profile was used in assaying cell surface density of antigen molecules. The density of B-L antigen on the cell surface is apparently low in immature and high in mature cells, whereas the density of Bu-1 antigen does not vary in cells at different maturational stages. The existence of B-L+ and Bu-1+ cells in chickens bursectomized at 60 h of embryonic development (Bx) is demonstrated, indicating that neither B-L or Bu-1 antigen is exclusively specific for cells differentiated in the bursa. The densities of B-L and Bu-1 molecules on lymphoid cells in Bx chickens are similar to those of controls. However, the number of B-L+ and Bu-1+ cells was decreased in Bx chickens. We conclude that the extrabursal site where Bx B cells mature has an ability similar to that of the bursa to induce and enhance the expression of B-L and Bu-1 antigens. However, only few B cells proliferate and/or are released into the circulation. Further, the extrabursal site unequivocally lacks the most important function of the bursa, the creation and expansion of antibody diversity.

Aging↗

Antibody-forming capacity of B cell-deficient chickens reconstituted with limiting numbers of B cell precursors.

To examine the antibody-forming capacity of neonatally cyclophosphamide-treated chickens reconstituted with limiting numbers of B cell precursors, we analyzed their antibody responses to six unrelated antigens. Our results demonstrate that about 10 x 10(6) bursal cells are needed in this adoptive cell transfer model to restore normal immune competence to B cell-deficient birds. From our earlier data we know that with low repopulating cell numbers (less than 10 x 10(6) cells) developing bursal follicles are of clonal origin. Ten million cells repopulate about 40%, i.e. about 4 x 10(3) of the bursal lymphoid follicles. Assuming the clonal origin of the follicles these results imply that the B cell system of birds receiving this dose is derived from less than 5 x 10(3) precursor cells. At the lowest reconstituting dose (1.25 x 10(6) cells) most birds do not respond to the antigens studied. However, their B cell system is derived from only about 500 precursor cells. Because the antibody repertoire of a normal chicken was estimated to be at least 10(6) our results suggest that each precursor gives rise to a large number (greater than 200) of immunoglobulin V-region gene variants during its clonal proliferation in the bursa. Our results are thus consistent with the proposed "hyperconversion" mechanism of generation of antibody diversity in the chicken and provide quantitative data useful for estimating what such somatic modification rates might be.

Animals↗

B cell precursors in chick embryos surgically bursectomized at 72 h of incubation.

To determine the presence of precursor B cells in chick embryos surgically bursectomized at 72 h of incubation (E-Bx) we studied chick chimeras that were produced by establishing parabiotic connections between blood vessels of chorioallantoic membranes of normal and surgically bursectomized chick embryos. Using sex chromosomes and a B cell alloantigen (Bu-1a) as markers we showed that chick embryos bursectomized at 72 h of incubation contain B cell precursors capable of colonizing the bursa of Fabricius and developing into B lymphocytes. The repopulation capacity of 14-day-old embryonic spleen cells from E-Bx recipients was tested by transferring them into age-matched X-irradiated Bu-1-disparate embryos. The results show that B cell precursors are present in 14-day spleen of chick embryos bursectomized at 72 h of incubation. These precursors carry the Bu-1 B cell alloantigen, suggesting that commitment to the B cell lineage can take place in the absence of bursa.

Age Factors↗

Monoclonal antibodies against chicken Bu-1a and Bu-1b alloantigens.

The production and characterization of monoclonal antibodies (mAbs) against chicken B cell surface alloantigens, Bu-1a and Bu-1b, is described. Flow cytometric analysis using these mAbs demonstrates that Bu-1 gene locus does not show allelic exclusion. Two color fluorescence analysis using simultaneous surface marker labeling and DNA staining shows that the expression of Bu-1 antigen is not restricted to a specific phase of the cell cycle. Earlier findings that Bu-1 locus is not linked to the MHC locus are confirmed. Furthermore, data is presented that Bu-1 antigen expression is not entirely B cell restricted. Apparently a fraction of larger mononuclear cells with typical light scatter characteristics in flow cytometry also bear this marker. MAbs against both allelic Bu-1 antigens are beneficial tools e.g. in typing of chicken lines and in studies on chicken B cell differentiation.

Animals↗