Biomedical subjects

O Vainio

Publications and source records attributed to O Vainio.

At least 37 records · Page 2Linked to original sources

PubMed1999

B and T cell immunity in patients with lysinuric protein intolerance.

Lysinuric protein intolerance (LPI) is characterized by defective cellular transport of the dibasic amino acids, secondary dysfunction of the urea cycle, aversion to dietary protein, failure to thrive, hepatosplenomegaly and osteoporosis. Because several patients have suffered from recurrent respiratory infections and/or severe generalized varicella, and a few have developed systemic lupus, vasculitis or other autoimmune diseases, we have now evaluated the function of patients' immune systems. Serum concentrations of one to three IgG subclasses were decreased in 10 of the 12 patients studied. Antibody titres against diphtheria, tetanus and Haemophilus influenzae (Hib) were below the detection limit of the assay in four, three and eight of the 11 patients examined, respectively. (Re)vaccination of these 11 patients led to satisfactory responses against tetanus, but two patients still failed to develop measurable antibodies against diphtheria, two against Hib and six against one or more of the three serotypes of 23-valent pneumococcus vaccine. The proportions of T cells of all lymphocytes and the proliferative responses of the peripheral blood mononuclear cells were normal. In conclusion, humoral immune responses in some patients with LPI are defective and these patients may benefit from intravenous immunoglobulin therapy.

Adult↗

PubMed1999

Pharmacokinetics of medetomidine in ponies and elaboration of a medetomidine infusion regime which provides a constant level of sedation.

The pharmacokinetics of intravenous (i.v.) medetomidine (7 mcg kg(-1)) were best described by a two-compartment model in five ponies. Total body clearance was 4 (SD 0.60) 1 kg h,(-1)t(1/2alpha)7. 6 (0.91) minutes and t(1/2beta)51.3 (13.09) minutes. In one pony the one-compartmental model was best fit, and total body clearance was 4. 2 l kg h(-1)and t(1/2)was 11 minutes. Medetomidine plasma levels had fallen below the limits of quantification (0.05 ng ml(-1)) within 4 hours. Medetomidine 5 mcg kg(-1)i.v. followed by an infusion of 3.5 mcg kg h(-1)for two hours provided a constant level of sedation reaching steady state plasma medetomidine levels of 1-1.5 ng ml(-1)within 30 minutes. Sedation was reversed effectively by atipamezole (60 mcg kg(-1)) i.v. The pharmacokinetics of medetomidine make it suitable for prolonged use by infusion, such as is required as part of a total intravenous anaesthetic technique in horses.

Animals↗

PubMed1999

Characterization of prethymic progenitors within the chicken embryo.

The thymic primordium in both birds and mammals is first colonized by cells emerging from the intra-embryonic mesenchyme but the nature of these precursors is poorly understood. We demonstrate here an early embryonic day 7 prethymic population with T lymphoid potential. Our work is a phenotypic analysis of, to date, the earliest embryonic prethymic progenitors arising in the avian para-aortic area during ontogeny. The phenotype of these cells, expressing the cell surface molecules alpha2beta1 integrin, c-kit, thrombomucin/MEP21, HEMCAM and chL12, reflects functional properties required for cell adhesion, migration and growth factor responsiveness. Importantly, the presence of these antigens was found to correlate with the recolonization of the recipient thymus following intrathymic cell transfers. These intra-embryonic cells were also found to express the Ikaros transcription factor, the molecular function of which is considered to be prerequisite for embryonic lymphoid development.

Animals↗

PubMed1999

Cross-reactive anti-chicken CD4 and CD8 monoclonal antibodies suggest polymorphism of the turkey CD8alpha molecule.

To measure turkey CD4 and CD8 T cell levels, the cross-reactivity of mouse anti-chicken CD4 and CD8 monoclonal antibodies (mAb) with turkey leucocytes was tested by flow cytometric analysis of blood obtained from individuals in five turkey lines. The turkey lines used included a randombred control population (RBC2), a subline (F) of RBC2 selected for increased 16-wk BW, and a sire line (A, B, and C) from each of three commercial turkey breeders. Peripheral blood lymphocytes were isolated and stained with single or dual color staining. The CT8 mAb (anti-chicken CD8alpha) failed to detect the CD8alpha molecule in some turkeys, and there were large line differences in ability to detect the CD8alpha molecule. However, certain anti-chicken CD8alpha mAb (3-298, 3-292, and 11-39) had good cross-reactivity with the turkey CD8alpha molecule. These present data indicate that the turkey CD8alpha molecule is polymorphic. Some anti-chicken CD4 mAb (CT4, 2-6, 2-35, and 7-125) were also cross-reactive with the turkey CD4 molecule. Immunoprecipitation and Western blotting showed that the 3-298 mAb precipitated a 33- to 35-kDa polypeptide from the turkey splenocyte lysate under reducing conditions. The availability of cross-reactive anti-chicken CD4 and CD8 mAb will facilitate the studies of immune responses in turkeys.

Animals↗

PubMed1998

Reversal of sedative and clinicophysiological effects of epidural xylazine and detomidine with atipamezole and yohimbine in buffaloes (Bubalus bubalis).

The sedative and clinicophysiological effects of either xylazine (0.1 mg/kg) or detomidine (50 micrograms/kg) administered epidurally to groups of five buffaloes were reversed by the intravenous administration of either yohimbine (0.125 mg/kg) or atipamezole (10 micrograms/kg). Epidural xylazine or detomidine produced bradycardia, respiratory depression, ruminal stasis and hypothermia and these effects were completely reversed within five to 15 minutes after the intravenous administration of atipamezole or yohimbine, with no signs of excitement or resedation. Atipamezole reversed the effects of xylazine or detomidine more rapidly than yohimbine.

Adrenergic alpha-Agonists↗

PubMed1998

Analysis of the immunological cross reactivities of 213 well characterized monoclonal antibodies with specificities against various leucocyte surface antigens of human and 11 animal species.

213 Monoclonal antibodies (mAbs) raised against leucocyte surface antigens from human and 11 animal species were analyzed for reactivities against leucocytes from human and 15 different animal species. We found 77 mAbs (36%) to cross-react. Altogether, 217 cross reactions were registered out of 3195 possible combinations (7%). Most of the cross reacting mAbs had integrin or MHC class II specificities. This study defined cross reactions on the following markers: CD1a, 1c, 2, 4, 5, 8, 9, 11a, 11b, 14, 18, 20, 21, 23, 29, 31, 41, 43, 44, 45, 45R, 46, 49, 61, 62L, TCR gamma/delta, BCR, Thy-1, MHC class I and MHC class II, Swine-WC7 and Cattle-WC1. In order to characterize the molecular weight (MW) of the corresponding cross reacting antigens, selected mAbs were used to immunoprecipitate the antigens. The MW's of the analyzed precipitated antigens were in good agreement with the MWs of the homologous antigens. The followed strategy was found to be efficient and economical in defining new leucocyte antigen reactive mAbs.

Animals↗

PubMed1998

Clinical efficacy and safety of propofol or ketamine anaesthesia in dogs premedicated with medetomidine.

Combinations of medetomidine with either propofol or ketamine were compared for the sedation and induction of anaesthesia in dogs undergoing a variety of surgical (60 per cent) and non-surgical (40 per cent) procedures. Eighty-four dogs were used at four sites. Medetomidine was administered intramuscularly at a dose of 1000 micrograms/m2 body surface area 10 to 15 minutes before the induction of anaesthesia by the administration of propofol (n = 44) or ketamine (n = 40) dosed to effect. The dogs became sedated by medetomidine after a mean (sd) time of 6.7 (5.4) minutes, and their heart rates and respiration rates decreased. Sixteen of the dogs suffered an adverse effect, 13 of them vomited. Anaesthesia was induced by the intravenous administration of propofol (2.1 [0.7] mg/kg) or ketamine (3.7 [1.9] mg/kg), and further doses of the anaesthetic were given, depending on the length of the operation, once in 17 per cent, twice in 11 per cent and three or more times in 24 per cent of the cases. The heart rate of the dogs anaesthetised with ketamine was significantly higher than that of the dogs anaesthetised with propofol, but there were no other significant physiological differences. There were 11 adverse side-effects in the ketamine group compared with five in the propofol group and they were generally more severe. The quality of the recovery from anaesthesia was considered to be smooth in 89 per cent of the propofol group but in only 63 per cent of the ketamine group.

Anesthesia↗

PubMed1998

The structure of avian CD5 implies a conserved function.

The chicken CD5 cDNA was isolated by COS cell expression cloning utilizing a novel mAb 2-191. The cDNA contains a 1422-nucleotide open reading frame encoding a mature protein with 32% and 30% identity to mouse and human CD5 polypeptides, respectively. The molecule consists of a 330-amino acid extracellular region with three repeats of the scavenger receptor cysteine-rich domain, a 29-amino acid hydrophobic transmembrane domain, and a 93-amino acid cytoplasmic tail. The cytoplasmic region contains motifs that are highly conserved between species, including several potential phosphorylation sites. The chicken CD5 is a 64-kDa phosphorylated glycoprotein with a protein core of 57 kDa as determined by immunoprecipitation and SDS-PAGE analysis. Alphabeta T cells express a homogeneously high level of CD5, whereas low or intermediate CD5 expression on gammadelta T cells depends on their tissue location. In contrast to human and mouse, CD5 is found at low levels on all chicken B cells. The high conservation of structural features, as well as signaling motifs, implies a conserved role for CD5 both in lymphocyte development and function.

Amino Acid Sequence↗

PubMed1998

CTX, a Xenopus thymocyte receptor, defines a molecular family conserved throughout vertebrates.

CTX, a cortical thymocyte marker in Xenopus, is an immunoglobulin superfamily (Igsf) member comprising one variable and one constant C2-type Igsf domain, a transmembrane segment and a cytoplasmic tail. Although resembling that of the TCR and immunoglobulins, the variable domain is not encoded by somatic rearrangement of the gene but by splicing of two half-domain exons. The C2 domain, also encoded by two exons, has an extra pair of cysteines. The transmembrane segment is free of charged residues, and the cytoplasmic tail (70 amino acids) contains one tyrosine and many glutamic acid residues. ChT1, a chicken homologue of CTX, has the same structural and genetic features, and both molecules are expressed on the thymocyte surface. We cloned new mouse (CTM) and human (CTH) cDNA and genes which are highly homologous to CTX/ChT1 but not lymphocyte specific. Similarity with recently described human cell surface molecules, A33 antigen and CAR (coxsackie and adenovirus 5 receptor), and a number of expressed sequence tags leads us to propose that CTX defines a novel subset of the Igsf, conserved throughout vertebrates and extending beyond the immune system. Strong homologies within vertebrate sequences suggest that the V and C2 CTX domains are scions of a very ancient lineage.

Amino Acid Sequence↗

PubMed1998

Inhibition of the development of spontaneous autoimmune thyroiditis in the obese strain (OS) chickens by in vivo treatment with anti-CD4 or anti-CD8 antibodies.

The involvement of CD4+ and CD8+ T cells in pathogenesis of spontaneous autoimmune thyroiditis (SAT) in obese strain (OS) chickens has not been studied in depth until now. We depleted CD4+ or CD8+ T cells in OS chickens by treatment with murine monoclonal anti-CD4 or anti-CD8 antibodies at 3 day intervals beginning at hatching. The birds were killed at 19-25 days of age. Treatment with anti-CD4 antibody completely prevented SAT development, while treatment with anti-CD8 antibody partially inhibited SAT. These results show the critical role of CD4+ T cells in the development of SAT in OS chickens, and indicate that CD8+ T cells are also involved in SAT pathogenesis.

Age Factors↗

PubMed1998

Comparison of three doses of dexmedetomidine with medetomidine in cats following intramuscular administration.

Cats (n = 6) were administered dexmedetomidine (DEX) and medetomidine (MED) at three different dose levels in a randomized, blinded, cross-over study. DEX was administered at 25, 50 and 75 microg/kg (D25, D50 and D75), corresponding to MED 50, 100 and 150 microg/kg (M50, M100 and M150). Sedation, analgesia and muscular relaxation were scored subjectively. Heart and respiratory rates and rectal temperature were measured. Corresponding doses of DEX and MED were compared. Effects were also compared between dose levels for each compound. At dose level 2 (D50-M100), the duration of effective clinical sedation was significantly shorter after DEX (202.5 +/- 16.0 min) than after MED (230.0 +/- 41.2 min). Proceeding from D50-M100 to D75-M150, the duration of effective clinical sedation was increased more after DEX (by 57.5 +/- 38.4 min) than after MED (by 14.2 +/- 41.9 min) Increasing from D50-M100 to D75-M150, heart rate was further decreased after DEX (by 8.1 +/- 13.4%) but not after MED. There was no statistically significant difference between corresponding doses of DEX and MED for any of the other parameters studied. Changes in sedation, analgesia and muscular relaxation were dose-dependent. It was concluded that anaesthetic effects of medetomidine in cats are probably due entirely to its d-isomer and that dexmedetomidine at 25, 50 and 75 microg/kg induces dose-dependent sedation, analgesia and muscular relaxation of clinical significance in cats.

Analgesics, Non-Narcotic↗

PubMed1998

Long-term treatment with GM-CSF in patients with chronic lymphocytic leukemia and recurrent neutropenic infections.

In this prospective study we evaluated the multiple effects of long-term GM-CSF therapy on blood counts, granulocyte functions and disease progression in patients with chronic lymphocytic leukemia (CLL) with chronic neutropenia and recurrent bacterial infections. The treatment duration varied from 2 to 12 weeks. The neutrophil count was raised in all patients, by the median of 6.6-fold. The neutrophil level of 1.0 x 10(9)/l was usually reached after two weeks. The initial dose of GM-CSF was 5 microg/kg/day, and 1-7 microg/kg/day was required to maintain the neutrophil level above 1.0 x 10(9)/l. Granulocyte functions, i.e. chemiluminescence (CL), random migration, and fMLP-stimulated chemotaxis were initially depressed in all patients when compared to healthy controls. GM-CSF enhanced significantly CL even when given at small doses (less than 1 microg/kg/day), even lower than the dose required to promote granulopoiesis. We conclude that GM-CSF is effective in improving CLL associated chronic neutropenia and also enhances impaired granulocyte chemiluminescence. Thus, GM-CSF could be helpful for giving chemotherapy without neutropenic delays and for prophylaxis of infectious complications in CLL patients.

Aged↗

PubMed1997

Ontogeny of the immune system: gamma/delta and alpha/beta T cells migrate from thymus to the periphery in alternating waves.

The embryonic thymus is colonized by the influx of hemopoietic progenitors in waves. To characterize the T cell progeny of the initial colonization waves, we used intravenous adoptive transfer of bone marrow progenitors into congenic embryos. The experiments were performed in birds because intravenous cell infusions can be performed more efficiently in avian than in mammalian embryos. Progenitor cells, which entered the vascularized thymus via interlobular venules in the capsular region and capillaries located at the corticomedullary junction, homed to the outer cortex to begin thymocyte differentiation. The kinetics of differentiation and emigration of the T cell progeny were analyzed for the first three waves of progenitors. Each progenitor wave gave rise to gamma/delta T cells 3 d earlier than alpha/beta T cells. Although the flow of T cell migration from the thymus was uninterrupted, distinct colonization and differentiation kinetics defined three successive waves of gamma/delta and alpha/beta T cells that depart sequentially the thymus en route to the periphery. Each wave of precursors rearranged all three TCR Vgamma gene families, but displayed a variable repertoire. The data indicate a complex pattern of repertoire diversification by the progeny of founder thymocyte progenitors.

Adoptive Transfer↗

PubMed1997

A novel peripheral CD4+ CD8+ T cell population: inheritance of CD8alpha expression on CD4+ T cells.

In this study we show the inheritance of a CD4+ CD8+ peripheral Tcell population in the H.B15 chicken strain. A large proportion of alphabeta T cells in peripheral blood (20-40%), spleen (10-20%) and intestinal epithelium (5-10%) coexpress CD4 and CD8alpha, but not CD8beta. CD4+ CD8alpha alpha cells are functionally normal T cells, since they proliferate in response to mitogens and signals delivered via the alphabeta T cell receptor as well as via the CD28 co-receptor. These cells induce in vivo a graft versus host-reaction, providing further evidence for their function as CD4+ T cells. The CD4+ CD8alpha alpha T cell population was found in 75% of the first progeny and in 100% of further progenies, demonstrating that coexpression of CD4 and CD8 on peripheral T cells is an inherited phenomenon. In addition, cross-breeding data suggest a dominant Mendelian form of inheritance. The hereditary expression of CD8alpha on peripheral CD4+ T cells in chicken provides a unique model in which to study the regulation of CD4 and CD8 expression.

Animals↗

PubMed1997

Polymorphism of chicken CD8-alpha, but not CD8-beta.

We report here the structural basis of CD8 polymorphism in the chicken. Three chicken strains (RPRL Line 7, H.B15.H7, and H.B15. H12) have 14 nucleotide differences in the CD8A cDNA sequence causing eight amino acid replacements in the extracellular part of the molecule. Only two amino acid replacements and four silent mutations were observed in the CD8B cDNA sequence in one (H7) of the strains. Substitutions in CD8alpha were solely responsible for the binding of CD8-specific monoclonal antibodies, as detected by cDNA expression in COS cells. The majority of the amino acid substitutions are located in the immunoglobulin V-like domain and three of the changes (residues 30, 34, and 58) are situated in the putative major histocompatibility complex class I binding CDR1 and CDR2 regions of the chicken CD8alpha. CD8A polymorphism has not been reported in other species and this suggests that CD8A and CD8B have evolved under different selective pressures in the chicken.

Amino Acid Sequence↗

PubMed1997

In vitro lymphocyte proliferation test in the diagnosis of oral mucosal hypersensitivity reactions to dental amalgam.

Patch testing was carried out in 23 patients with oral lichenoid lesions (OLL) topographically related to dental amalgam fillings. Twelve patients displayed positive reactions to several mercury compounds, whereas 11 patients were negative. An in vitro lymphocyte proliferation (LyPro) test was carried out using different mercury compounds and other metal salts. Mercuric chloride and phenyl mercuric acetate caused positive proliferation in 3/12 patch test-positive and in 5/11 negative patients. One out of seven healthy control subjects had a positive LyPro result. The mean stimulation index (SI) values between the patient groups or compared with the control subjects did not differ significantly. Zinc, tin, copper or silver salts caused in vitro lymphocyte stimulation in most of the patients and in healthy control people. Total (14) or partial (4) replacement of amalgam fillings was carried out in 18 patients. Complete healing of lichenoid lesions was seen in 4/6 LyPro test-positive and in 5/10 patch test-positive patients at follow-up examinations 12 months after the replacement of amalgam fillings. The in vitro proliferation assay seems not to be a specific test for identifying the patients who would benefit from amalgam replacement.

Adult↗

PubMed1996

Thymocyte emigration in the chicken: an over-representation of CD4+ cells over CD8+ in the periphery.

We have examined the emigration of chicken thymocytes after intrathymic fluorescein isothiocyanate (FITC) labelling in situ. In this paper we show that in young birds about 0.7% and 0.4% of thymocytes emigrate from the thymus to the blood and the spleen, respectively, per day. This suggests that, as in mammals, most thymocytes die within the thymus. At 3 weeks of age gamma delta and alpha beta T cells leave the thymus in comparable levels to their appearance in the blood. The phenotype of recent emigrants in peripheral tissues is similar to that of mature T cells. Interestingly, recent emigrants contain relatively much higher numbers of CD4+ and fewer CD8+ cells than is observed in peripheral tissues in a steady-state situation.

Animals↗

PubMed1996

HEMCAM, an adhesion molecule expressed by c-kit+ hemopoietic progenitors.

We have characterized the adhesion molecule HEMCAM, which is expressed by hemopoietic progenitors of embryonic bone marrow. HEMCAM belongs to the immunoglobulin superfamily and consists of the V-V-C2-C2-C2 Ig domains. There are three mRNA splice variants. One has a short cytoplasmic tail; another has a long tail; while the third seems to lack transmembrane and cytoplasmic regions. Except for the NH2-terminal sequence, HEMCAM is identical to gicerin, a molecular involved in neurite outgrowth and Wilm's kidney tumor progression in the chicken and it is significantly homologous with MUC18 a molecule involved in melanoma progression and metastasis in human beings. In the bone marrow the HEMCAM+ cell population contains c-kit+ subsets. HEMCAM+ cells coexpressing the receptor tyrosine kinase c-kit give rise to T cells at a frequency of 0.17 when injected intrathymically in congenic animals. As HEMCAM+, c-kit+ cells differentiate into myeloid and erythroid CFU's the double-positive cell population seems to contain precursors for multiple lineages. HEMCAM promotes cell-cell adhesion of transfected cells. Cross-linking of murine HEMCAM leads to cell spreading of T-lymphocyte progenitors adhering to the vascular adhesion molecules, PECAM-1 and VCAM-1. Thus, HEMCAM is likely to be involved in cellular adhesion and homing processes.

Amino Acid Sequence↗