Biomedical subjects

C Johansson

Publications and source records attributed to C Johansson.

At least 19 recordsLinked to original sources

PubMed2001

Improved bone-screw interface with hydroxyapatite coating: an in vivo study of loaded pedicle screws in sheep.

STUDY DESIGN: An in vivo sheep model with loaded pedicle screws was used, wherein each animal served as its own control. OBJECTIVES: To examine the effects of hydroxyapatite (HA) coating on the bone-to-implant interface in loaded spinal instrumentations. SUMMARY OF BACKGROUND DATA: Spinal instrumentation improves the healing rate in spinal fusion, but screw loosening constitutes a problem. HA coating of other implants has resulted in favorable effects on the bone-to-implant interface. METHODS: Nine sheep were operated on with destabilizing laminectomies at two levels: L2-L3 and L4-L5. Each level was stabilized separately with a four-screw instrumentation. Uncoated screws (stainless steel) or the same type of screws coated with plasma-sprayed HA were used in either the upper or the lower instrumentation in a randomized fashion. The animals were killed at 6 or 12 weeks after surgery. The specimens were embedded in resin, ground to approximately 10 microm, and stained with toluidine blue. Histomorphometric evaluation was carried out in a Leitz Aristoplan (Wetzlar, Germany) light microscope equipped with a Leitz Microvid unit. RESULTS: The average percentage of bone-to-implant contact after 6 weeks was 69 +/- 10 for the HA-coated screws and 18 +/- 11 for the uncoated screws (P < 0.03), and after 12 weeks 64 +/- 31 (HA-coated) and 9 +/- 13 (uncoated, P < 0.02). The average bone volume in the area close to the screw was significantly higher for the HA-coated screws at both 6 and 12 weeks. CONCLUSIONS: HA coating improved the bone-to-implant interface significantly, indicating that HA coating can become useful for improving the purchase of pedicle screws.

Animals↗

PubMed2001

Altered dopaminergic transmission in the anorexic anx/anx mouse striatum.

We demonstrate abnormal dopaminergic neurotransmission in anorexic mice, homozygous for a recessive mutation (anx) causing starvation and motor disturbances. Isolated neurons from anx/anx striatum displayed a markedly increased activity of the Na+,K+-ATPase compared with normal littermates. Dopamine down-regulates Na+,K+-ATPase activity in striatal medium spiny neurons in rat, mouse and guinea pig. However, addition of dopamine in vitro failed to suppress the increased activity in anx/anx striatal neurons. Striatal dopamine and its metabolites, but not norepinephrine, were slightly but significantly lower in anx/anx mice than in normal littermates. We suggest that abnormal dopaminergic transmission may contribute to the anx phenotype.

Animals↗

PubMed2001

Cloning and expression of a novel human glutaredoxin (Grx2) with mitochondrial and nuclear isoforms.

Glutaredoxin (Grx) is a glutathione-dependent hydrogen donor for ribonucleotide reductase. Today glutaredoxins are known as a multifunctional family of GSH-disulfide-oxidoreductases belonging to the thioredoxin fold superfamily. In contrast to Escherichia coli and yeast, a single human glutaredoxin is known. We have identified and cloned a novel 18-kDa human dithiol glutaredoxin, named glutaredoxin-2 (Grx2), which is 34% identical to the previously known cytosolic 12-kDa human Grx1. The human Grx2 sequence contains three characteristic regions of the glutaredoxin family: the dithiol/disulfide active site, CSYC, the GSH binding site, and a hydrophobic surface area. The human Grx2 gene, located at chromosome 1q31.2--31.3, consisted of five exons that were transcribed to a 0.9-kilobase human Grx2 mRNA ubiquitously expressed in several tissues. Two alternatively spliced Grx2 mRNA isoforms that differed in their 5' region were identified. These corresponded to alternative proteins with a common 125-residue C-terminal Grx domain but with different N-terminal extensions of 39 and 40 residues, respectively. The 125-residue Grx domain and the two full-length variants were expressed in E. coli and exhibited GSH-dependent hydroxyethyl disulfide and dehydroascorbate reducing activities. Western blot analysis of subcellular fractions from Jurkat cells with a specific anti-Grx2 antibody showed that human Grx2 was predominantly located in the nucleus but also present in the mitochondria. We further showed that one of the mRNA isoforms corresponding to Grx2a encoded a functional N-terminal mitochondrial translocation signal.

Amino Acid Sequence↗

PubMed2001

Determination of absolute configuration of (pi-allyl) palladium complexes by NMR spectroscopy and stereoselective complexation.

The chiral chelating ligand N,N'-bis(phenylethyl)bispidine (1) forms a rigid cavity which accommodates (pi-allyl)palladium species with high selectivity. In the resulting complex, the absolute configuration of the pi-allyl ligand can be determined by the detection in NMR spectra of a few unambiguous interligand NOEs. Dynamic processes involving the pi-allyl ligand can be investigated. Depending on the analytical target, ligand (S,S)-1 or (R,R)-1 may be used.

Journal Article↗

PubMed2001

The role of different protein components from the Haemophilus ducreyi cytolethal distending toxin in the generation of cell toxicity.

Cytolethal distending toxin of Haemophilus ducreyi (HdCDT) is a multicomponent toxin, encoded by an operon consisting of three genes, cdtABC. To investigate the role of the individual products in generation of toxicity, recombinant plasmids were constructed allowing expression of each of the genes individually or in different combinations in Escherichia coli and Vibrio cholerae. Expression of all three genes (cdtABC) was necessary to generate toxicity on cells, and no activity was obtained using combinations in which only one or two of the genes were expressed. Of the individual gene products, the CdtA was shown to exist in two forms with an MW of 23 and 17 kDa, respectively. The CdtB protein alone resulted in DNase activity. CdtC purified from both toxic and non-toxic extracts (from strains expressing cdtCAB and cdtC, respectively) had a molecular weight of about 20 kDa and reacted with a CdtC-specific monoclonal antibody. However, the protein isoelectric point (pI) of CdtC from toxic preparations was about 1.5 pH units more basic than from non-toxic ones. Both forms were immunogenic giving rise to toxin-neutralizing antibodies. Toxicity was reconstructed by combining non-toxic cell sonicates from E. coli, expressing CdtA, CdtB and CdtC proteins individually. Only combinations including all three products gave toxicity, indicating that all are actively involved in the generation of toxic activity on cells. The reconstruction resulted in a 1.5 pH unit shift in the PI of CdtC, making it identical to that of the protein isolated from bacteria expressing cdtABC. The results showed that the CdtB component produces DNase activity, but cell toxicity depends on the involvement of the other two components of CDT and is associated with absorption of all three proteins by HEp-2 cells.

Bacterial Proteins↗

PubMed2001

Salmonella typhimurium-induced cytokine production and surface molecule expression by murine macrophages.

The influence of Salmonella enterica serovar Typhimurium (S. typhimurium) on co-stimulatory molecule expression, cytokine production and induction of nitric oxide synthase (iNOS) by murine macrophages (Mphi), as well as the influence of the phoP locus on these aspects of S. typhimurium-Mphi interaction, was characterized. Pulsing Mphi with S. typhimurium resulted in increased surface expression of MHC-I, MHC-II, CD86 and CD54. Furthermore, co-incubating S. typhimurium with Mphi resulted in interleukin (IL)-12p40, IL-6 and tumor necrosis factor-alpha production as well as iNOS induction while IL-12p70 was not detectable. Finally, although phoP did not influence the level of surface molecule expression or cytokine production by S. typhimurium-pulsed Mphi phoP did influence the level of iNOS induction. Together these data show that S. typhimurium interaction with Mphi activates these cells in ways that may enhance their ability to productively stimulate Salmonella-specific T cells following phagocytic processing and presentation of Salmonella antigens.

Animals↗

PubMed2001

Seasonal affective disorder and serotonin-related polymorphisms.

Disturbances in central serotonergic systems have been hypothesized to be involved in seasonal affective disorder (SAD). Association between SAD and the shorter allele of the serotonin transporter promoter repeat length polymorphism (5-HTTLPR) has been reported in an American sample. We have genotyped 82 SAD patients and 82 healthy controls from Sweden, Finland, and Germany for this and five other polymorphisms in the genes coding for serotonin receptors 5-HT2A and 5-HT2C, tryptophan hydroxylase and white. No associations with SAD or seasonality (seasonal variations in mood and behavior) were detected. Although minor effects cannot be excluded, our results suggest that these polymorphisms do not play a major role in the pathogenesis of SAD in the northern European population.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed2001

Osteoinduction, osteoconduction and osseointegration.

Osteoinduction is the process by which osteogenesis is induced. It is a phenomenon regularly seen in any type of bone healing process. Osteoinduction implies the recruitment of immature cells and the stimulation of these cells to develop into preosteoblasts. In a bone healing situation such as a fracture, the majority of bone healing is dependent on osteoinduction. Osteoconduction means that bone grows on a surface. This phenomenon is regularly seen in the case of bone implants. Implant materials of low biocompatibility such as copper, silver and bone cement shows little or no osteoconduction. Osseointegration is the stable anchorage of an implant achieved by direct bone-to-implant contact. In craniofacial implantology, this mode of anchorage is the only one for which high success rates have been reported. Osseointegration is possible in other parts of the body, but its importance for the anchorage of major arthroplasties is under debate. Ingrowth of bone in a porous-coated prosthesis may or may not represent osseointegration.

Bone Development↗

PubMed2001

Synthesis and structure elucidation of some new thioether derivatives of 1,2,4-triazoline-3-thiones and their antimicrobial activities.

5-(4-Pyridinyl)-4-substituted-2.4-dihydro-3H-1,2,4-triazole-3-thiones and 5-(4-pyridinyl)-4-substituted-3-(benzoylmethyl)thio-4H-1,2,4-triazoles were synthesized. The structures of original nine compounds were confirmed by IR, 'H NMR, mass spectral methods and elemental analysis. The antibacterial, antifungal and antimycobacterial activities, together with those of known intermediate 1,4-disubstituted thiosemicarbazides, were reported.

Anti-Bacterial Agents↗

PubMed2001

Genetics of affective disorders.

Despite substantial evidence for heritability in affective disorders the contributing genes have proven elusive. Here we discuss the genetic epidemiology of depression, as well as methodological issues and results from molecular genetic studies. There has been rapid advances in genetics, genomics and statistical modelling, facilitating the search for molecular mechanisms underlying affective disorders and several strategies reviewed in this paper hold promise to provide progress in the field. Considering the poorly understood biological basis of vulnerability to affective disorders, the identification of genes involved in the pathophysiology will unravel mechanisms and pathways that could permit more personalized therapeutic strategies and result in new targets for pharmacological intervention.

Animals↗

PubMed2001

T cell responses to recombinant isoforms, synthetic peptides and a mutant variant of Lep d 2, a major allergen from the dust mite Lepidoglyphus destructor.

BACKGROUND: The dust mite Lepidoglyphus destructor is an important cause of allergic reactions to dust, especially in farming environments. Two isoforms, recombinant (r)Lep d 2.01 and rLep d 2.02, of the major allergen Lep d 2, have previously been expressed as recombinant proteins. These isoforms differ 10.4% at the amino acid level. Furthermore, a mutant form of Lep d 2.01 (rLep d 2.6Cys) with a highly reduced IgE reactivity, has also been produced. OBJECTIVE: To investigate the T cell responses to the recombinant isoforms of Lep d 2, the Lep d 2.6Cys mutant and peptides of Lep d 2, in allergic and non-allergic individuals. METHODS: Peripheral blood mononuclear cells from 18 allergic and 16 non-allergic individuals were stimulated with the different antigens and the proliferative responses were measured. The cytokine production (interleukin (IL)-4, IL-5 and interferon (IFN)-gamma) were measured by ELISA. RESULTS: Higher T cell proliferation was measured to isoform 01 than to 02 in 28/34 subjects. The responses to rLep d 2.6Cys were lower than to isoform 01 in most subjects, but higher than to Lep d 2.02. Two immuno-dominant peptides, corresponding to amino acid residue 11-25 and 61-75 were identified. The atopic subjects produced significantly lower IFN-gamma in response to Lep d 2.01 as compared to the non-atopics. CONCLUSIONS: There was a significant difference in T cell response between the two isoforms of rLep d 2. The hypoallergenic mutant rLep d 2.6Cys was able to evoke a T cell response with a magnitude which is between the two isoforms. Amino acid residue 11-25 and 61-75 are the most frequently recognized parts of Lep d 2 and are likely to contain the immuno-dominant T cell epitopes.

Adult↗

PubMed2001

Vertebral deformation in urban Swedish men and women: prevalence based on 797 subjects.

Vertebral fracture-deformation, a common feature of osteoporosis, shows considerable age, sex and geographical variation. We present the prevalence in an urban population of south-west Sweden. Lateral spine radiographs of 797 men and women, age 50-86 years, were evaluated by morphomety. The age-standardized prevalence of subjects with vertebral deformation using the deformation criterion -3 SD was 39 (95%CI 34-43)% in women and 33 (95%CI 28-38)% in men. The prevalence increased with age in both sexes. After adjustment for age, women had a higher prevalence than men, odds ratio 1.4. The proportion of vertebrae with deformation ranged from 2%-11%, increasing with age. The vertebrae most commonly deformed were Th 11, Th 12 and L1.

Age Factors↗

PubMed2001

Growth of costochondral grafts in reconstruction of the mandibular condyle: an experimental study in domestic pigs.

Reconstruction of the mandibular condyle with costochondral grafts (CCGs) in children may result in overgrowth at the reconstructed side of the mandible. In this study we report on the effects of functional stimuli on growth and morphology of growth plates of CCGs used for immediate mandibular condyle replacement in 10 juvenile pigs. The mandibular condyles were resected unilaterally and immediately reconstructed with autogenous CCGs. Another CCG was placed submuscularly on one tibia. The lengths of both CCGs and of one rib before resection were measured at operation and 12 weeks later. The grafts were labelled with intraperitoneal injections of oxytetracycline and alizarin eight and 12 weeks postoperatively, respectively. The extent of growth of the CCGs in the two environments was similar, so we concluded that the functional stimuli in the TMJ environment had only a minor influence on the extent of growth of the CCGs. The morphology of the growth plate of the CCGs had changed considerably.

Animals↗

PubMed2001

The influence of curli, a MHC-I-binding bacterial surface structure, on macrophage-T cell interactions.

Escherichia coli express thin surface fimbriae called curli which bind soluble matrix proteins and major histocompatibility complex (MHC)-I molecules. The present study addressed the ability of purified curli or curliated E. coli to influence peptide presentation on MHC-I, T cell proliferation and bacterial uptake by macrophages. In vitro studies with curli-proficient E. coli YMel and the isogenic curli-deficient strain YMel-1, both expressing the model antigen Crl-OVA, showed that curli expression by E. coli does not appear to influence the efficiency by which the bacteria are processed by murine macrophages for OVA(257-264) presentation on K(b). Furthermore, curli expression by E. coli did not influence the binding of exogenously added OVA(257-264) peptide to K(b) on the surface of prefixed macrophages. In addition, neither curliated nor non-curliated heat-killed bacteria influenced proliferation of either murine or human T cells stimulated with anti-CD3. Finally, curliated E. coli adhered to and were internalized by macrophages from C57BL/6 and MHC-I-deficient TAP1(-/-) mice equally well. Together these studies show that curli expression by E. coli does not appear to influence phagocytic processing of bacteria expressing Crl-OVA for OVA(257-264)/K(b) presentation, the binding of exogenously added OVA(257-264) to K(b) or T cell proliferation. In addition, although curli expression by E. coli enhances bacterial interaction with macrophages, curli interaction with MHC-I does not significantly contribute to this adherence.

Animals↗

PubMed2001

Translational and structural requirements of the early nodulin gene enod40, a short-open reading frame-containing RNA, for elicitation of a cell-specific growth response in the alfalfa root cortex.

A diversity of mRNAs containing only short open reading frames (sORF-RNAs; encoding less than 30 amino acids) have been shown to be induced in growth and differentiation processes. The early nodulin gene enod40, coding for a 0.7-kb sORF-RNA, is expressed in the nodule primordium developing in the root cortex of leguminous plants after infection by symbiotic bacteria. Ballistic microtargeting of this gene into Medicago roots induced division of cortical cells. Translation of two sORFs (I and II, 13 and 27 amino acids, respectively) present in the conserved 5' and 3' regions of enod40 was required for this biological activity. These sORFs may be translated in roots via a reinitiation mechanism. In vitro translation products starting from the ATG of sORF I were detectable by mutating enod40 to yield peptides larger than 38 amino acids. Deletion of a Medicago truncatula enod40 region between the sORFs, spanning a predicted RNA structure, did not affect their translation but resulted in significantly decreased biological activity. Our data reveal a complex regulation of enod40 action, pointing to a role of sORF-encoded peptides and structured RNA signals in developmental processes involving sORF-RNAs.

Base Sequence↗

PubMed2001

Photopheresis at onset of type 1 diabetes: a randomised, double blind, placebo controlled trial.

BACKGROUND: In recent years photopheresis, an extracorporeal form of photochemotherapy using psoralen and ultraviolet A irradiation of leucocytes, has been claimed to be an effective form of immunomodulation. AIM: To evaluate its effect in type 1 diabetes we performed a double blind, controlled study using placebo tablets and sham pheresis in the control group. METHODS: A total of 49 children, aged 10-18 years of age at diagnosis of type 1 diabetes were included; 40 fulfilled the study and were followed for three years (19 received active treatment with photopheresis and 21 placebo treatment). RESULTS: The actively treated children secreted significantly more C peptide in urine during follow up than control children. C peptide values in serum showed corresponding differences between the two groups. The insulin dose/kg body weight needed to achieve satisfactory HbA1c values was always lower in the photopheresis group; there was no difference between the groups regarding HbA1c values during follow up. The treatment was well accepted except for nausea (n = 3) and urticaria (n = 1) in the actively treated group. There were no differences regarding weight or height, or episodes of infection between the two groups during follow up. CONCLUSION: Photopheresis does have an effect in addition to its possible placebo effect, shown as a weak but significant effect on the disease process at the onset of type 1 diabetes, an effect still noted after three years of follow up.

Adolescent↗

PubMed2001

Food increases the bioavailability of tolterodine but not effective exposure.

The objective of this study was to investigate the influence of food on the pharmacokinetics of tolterodine, its active 5-hydroxymethyl metabolite (5-HM), and exposure to the active moiety (sum of unbound tolterodine + 5-HM) in healthy volunteers. Serum concentrations of tolterodine and 5-HM were measured for up to 12 hours after a single oral dose (2 mg) of tolterodine L-tartrate, administered either on an empty stomach or with a standardized medium-fat breakfast. All 23 subjects completing the study were classified as extensive metabolizers (phenotyped with debrisoquine). Pharmacokinetic data on tolterodine and the active moiety were evaluable for 22 subjects; all completing subjects were evaluable for 5-HM pharmacokinetics. Based on Cmax and AUC(infinity) ratios, relative bioavailability of tolterodine in the presence of food was 1.49 (90% confidence interval [CI], 1.35-1.71) and 1.53 (1.35-1.72), respectively. The pharmacokinetics of 5-HM and the active moiety were unaffected by food, as were the rates of drug absorption and terminal half-lives of tolterodine and 5-HM. Given that bioequivalence was observed for the active moiety underfed and fasting conditions, the authors concluded that coadministration of tolterodine with food is not expected to have any clinically relevant effects.

Adult↗

PubMed2001

Ablation of TRalpha2 and a concomitant overexpression of alpha1 yields a mixed hypo- and hyperthyroid phenotype in mice.

Thyroid hormone governs a diverse repertoire of physiological functions through receptors encoded in the receptor genes alpha and beta, which each generate variant proteins. In mammals, the alpha gene generates, in addition to the normal receptor TRalpha1, a non-hormone-binding variant TRalpha2 whose exact function is unclear. Here, we present the phenotype associated with the targeted ablation of TRalpha2 expression. Selective ablation of TRalpha2 resulted in an inevitable, concomitant overexpression of TRalpha1. Both TRalpha2 +/- and -/- mice show a complex phenotype with low levels of free T3 and free T4, and have inappropriately normal levels of TSH. The thyroid glands exhibit mild morphological signs of dysfunction and respond poorly to TSH, suggesting that the genetic changes affect the ability of the gland to release thyroid hormones. However, the phenotype of the mutant mice also has features of hyperthyroidism, including decreased body weight, elevated heart rate, and a raised body temperature. Furthermore, TRalpha2-/- and TRalpha2+/- mice are obese and exhibit skeletal alterations, associated with a late-onset growth retardation. The results thus suggest that the overexpression of TRalpha1 and the concomitant decrease in TRalpha2 expression lead to a mixed hyper- and hypothyroid phenotype, dependent on the tissue studied. The phenotypes suggest that the balance of TRalpha1:TRalpha2 expressed from the TRalpha gene provides an additional level of tuning the control of growth and homeostasis in mammalian species.

Animals↗