Biomedical subjects

T Olsson

Publications and source records attributed to T Olsson.

At least 37 records · Page 2Linked to original sources

PubMed2002

Testosterone and diurnal rhythmicity of leptin, TNF-alpha and TNF-II receptor in insulin-resistant myotonic dystrophy patients.

OBJECTIVE: To investigate the leptin and TNF systems in relation to testosterone in insulin resistant myotonic dystrophy (DM1) subjects. DESIGN AND SUBJECTS: Fasting morning samples and diurnal sampling during 24 h. Forty-two DM1 subjects (20 women and 22 men; age 41.5 (28.5-58.7) y, body mass index (BMI) 23.3 (18.6-29.2) kg/m(2); median and 10th and 90th percentile, respectively). Fifty healthy volunteers (23 women and 27 men; age 42 (27.0-56.9) y, BMI 24.0 (20.7-29.7) kg/m(2)). Nine men with DM1 and nine healthy men participated in diurnal sampling. MEASUREMENTS: Body composition was measured by bioelectric impedance analysis. Circulating levels of leptin, TNF-alpha, TNFR-II, insulin, testosterone and lipids were measured. The number of CTG triplet repeats was analysed. RESULTS: Basal as well as median 24 h levels of leptin and TNFR-II were significantly increased in DM1 patients, independent of body fat mass. This was associated with higher insulin and lower testosterone levels in DM1 patients. The genetic defect was related to leptin and TNFR-II levels in DM1 patients. CONCLUSION: Hyperleptinemia in DM1 is clearly linked to the concomitant hypogonadism. The genetic defect may directly or indirectly contribute to increased leptin levels. Increased exposure of cytokines may contribute to insulin resistance and other hormonal disturbances in DM1.

Adult↗

PubMed2002

Differential expression of neurotrophic factors and inflammatory cytokines by myelin basic protein-specific and other recruited T cells infiltrating the central nervous system during experimental autoimmune encephalomyelitis.

Recent evidence suggests that autoimmune reactions in the central nervous system (CNS) not only have detrimental consequences but can also be neuroprotective, and that this effect is mediated by the expression of neuronal growth factors by infiltrating leucocytes. Here we dissect these two phenomena in guinea pig myelin basic protein peptide (gpMBP 63-88)-induced experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Real-time TaqMan polymerase chain reaction (PCR) was used to measure mRNA for the nerve growth factors, brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3. As reference, the well-known proinflammatory mediator molecules interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha were quantified. In whole lumbar cord tissue, both the nerve growth factors and the proinflammatory cytokines, IFN-gamma and TNF-alpha, displayed similar expression patterns, peaking at the height of the disease. Among the infiltrating inflammatory cells isolated and sorted from the CNS, alphabeta+/T-cell receptor (TCR)BV8S2+, but not alphabeta+/TCRBV8S2-, recognized the encephalitogenic MBP peptide. Interestingly, these two populations displayed contrasting expression patterns of nerve growth factors and proinflammatory cytokines with higher inflammatory cytokine mRNA levels in alphabeta+/TCRBV8S2+ cells at all time intervals, whereas the levels of BDNF and NT3 were higher in alphabeta+/TCRBV8S2- cells. We conclude that a potentially important neuroprotective facet of CNS inflammation dominantly prevails within other non-MBP peptide-specific lymphoid cells and that there are independent regulatory mechanisms for neurotrophin and inflammatory cytokine expression during EAE.

Amino Acid Sequence↗

PubMed2002

The association between leptin and proinsulin is lost with central obesity.

OBJECTIVE: Hyperproinsulinaemia and hyperleptinaemia are interrelated features of the insulin resistance syndrome that are linked to the prospective risk of cardiovascular diseases. Whether the association between leptin and proinsulin is different between groups displaying different degrees of risk for cardiovascular diseases is not known. We therefore examined this association in men versus women and in pre- versus postmenopausal women from a population-based sample. DESIGN AND SUBJECTS: Healthy subjects (n = 158; 85 men and 73 pre- and postmenopausal women) from the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease population were studied with a cross-sectional design. METHODS: Anthropometric measurements (body mass index and waist circumference) and oral glucose tolerance tests were performed. Enzyme-linked immunosorbent assays were used for the analyses of specific insulin and proinsulin, and radioimmunoassay for leptin. Insulin resistance and beta-cell function were calculated according to the homeostasis assessment model. Partial correlation coefficients adjusted for age and measures of adiposity were calculated and multiple linear regression analyses were performed with leptin as dependent variable. RESULTS: In nonobese men and premenopausal women and in obese postmenopausal women, leptin was significantly associated with proinsulin after stratification for waist circumference. Furthermore, a multivariate analyses taking age and measures of adiposity into account, showed that high fasting proinsulin was a significant predictor of high leptin in these groups. In contrast, this association was lost with increasing central obesity in men and premenopausal women. CONCLUSIONS: This study shows that both the degree of adiposity and the hormonal milieu influence the association between circulating leptin and proinsulin in a normal population. Therefore, the insulin resistance syndrome seems to be characterized by lost association between leptin and proinsulin, which may be explained by dysfunction in the adipoinsular axis.

Abdomen↗

PubMed2002

Fc receptors are critical for autoimmune inflammatory damage to the central nervous system in experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is simulated by various forms of experimental autoimmune encephalomyelitis, in which T cells, antibodies, cytokines and complementary factors interact with the central nervous system (CNS) myelin proteins and lead to inflammatory damage. We investigated the role of Fc receptors (FcRs), which link the cellular and humoral branches of the immune system, in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), using two different FcRgamma knockout DBA/1 mice. The first knockout were the FcRgamma chain-deficient mice, which lack FcgammaRI, FcgammaRIII and Fc(epsilon)RI, while the second knockout mice lack only FcgammaRII. The lack of FcgammaRII enhanced the disease susceptibility with associated increased CNS demyelination. While FcRgamma+/+ DBA/1 mice also developed pronounced CNS infiltration and myelin destruction, FcRgamma-/- littermates were protected despite initial peripheral autoimmune responses to MOG. In vitro analyses revealed equivalent potentials of fluid phase phagocytosis of myelin and MOG in bone-marrow macrophages derived from both FcRgamma+/+ and FcRgamma-/- mice, while MOG-immunoglobulin (Ig)G immune complexes were only internalized by FcRgamma+/+ macrophages. This was associated with cellular activation in FcRgamma+/+ but not FcRgamma-/- macrophages, as assessed by the activation of intracellular mitogen activated protein (MAP)-kinase signalling elements. We propose that protection from EAE in FcRgamma-deficient mice is due to the inefficient antigen processing/presentation of myelin proteins during the induction of secondary immune responses locally in the CNS, which leads to demyelination. This demonstrates the importance of FcR in the promotion of autoimmune inflammation of the CNS and highlights the therapeutic possibility of treatment of MS with FcR-directed modalities.

Animals↗

PubMed2001

Statistical molecular design, parallel synthesis, and biological evaluation of a library of thrombin inhibitors.

A library of thrombin inhibitors has been designed using statistical molecular design. An aromatic scaffold was used, with three varied positions corresponding to three pockets at the active site of thrombin (the S-, P-, and D-pockets). The selection was performed in the building block space, and previously acquired data were included in the design procedure. The design resulted in six, four, and six building blocks for the first (S), second (P), and third (D) pockets, respectively. A second round of selection applied to the combined selected building blocks resulted in a subset of 18 compounds. The selected library was synthesized in parallel and biologically evaluated. The compounds were analyzed with respect to their inhibition (pIC(50)) of thrombin; membrane permeability, estimated by migration behavior in micellar media (CE log k') and pK(a); and specificity with respect to inhibition (K(i)) of trypsin. Multivariate QSAR studies of the responses yielded valuable results and information that could only be found using statistical molecular design in combination with multivariate analysis.

Animals↗

PubMed2001

Polygenic control of autoimmune peripheral nerve inflammation in rat.

Experimental autoimmune neuritis (EAN) is the principal animal model for Guillain-Barré syndrome (GBS), an inflammatory disease of the peripheral nervous system. Little is known on the genetic regulation of these diseases. We provide the first genetic linkage analysis of EAN. Susceptibility to EAN in a rat F2 population segregated with high levels of anti-PNM IgG, as well as IgG2b and IgG2c isotype levels, which support that disease genes regulate preferential Th1/Th2 differentiation. Linkage analysis demonstrated co-localization of EAN loci with reported susceptibility loci for experimental arthritis and/or encephalomyelitis and a new region on chromosome 17. Further dissection of these loci may disclose disease pathways in GBS.

Animals↗

PubMed2001

Alpha 1-adrenergic modulation of metabotropic glutamate receptor-induced calcium oscillations and glutamate release in astrocytes.

Astrocytic responses to activation of metabotropic glutamate receptors group I (mGluRs I) and alpha(1)-adrenoreceptors in cultured cells have been assessed using spectral analyzes and calcium imaging. Concentration-dependent changes were observed after stimulation with the mGluR I agonist (S)-3,5-dihydroxyphenylglycine (DHPG). These responses changed from a regular low frequency signal with sharp peaks at 1 microm to a pronounced stage of irregularity at 10 microm. After stimulation with 100 microm the signal was again homogenous in shape and regularity but occurred at a higher frequency. In contrast, the spectral properties after stimulation with the alpha(1)-adrenoreceptor agonist phenylephrine, exhibited considerable variation for all investigated concentrations. DHPG-induced increases in [Ca(2+)](i) were also associated with astroglial glutamate release, whereas no release was observed after noradrenergic stimulation. Both DHPG-mediated calcium signaling and glutamate release were inhibited by preincubation with 10 or 100 microm phenylephrine. Collectively, the present investigation provides new information about the spatial-temporal characteristics of astroglial intracellular calcium responses and demonstrates distinct differences between noradrenergic and glutamatergic receptors regarding intracellular calcium signaling and coupling to glutamate release. The noradrenergic modulation of DHPG-induced responses indicates that intracellular astroglial processes can be regulated in a bi-directional feedback loop between closely connected astrocytes and neurons in the central nervous system.

Animals↗

PubMed2001

MHC class II-regulated central nervous system autoaggression and T cell responses in peripheral lymphoid tissues are dissociated in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis.

We dissected the requirements for disease induction of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis in MHC (RT1 in rat) congenic rats with overlapping MOG peptides. Immunodominance with regard to peptide-specific T cell responses was purely MHC class II dependent, varied between different MHC haplotypes, and was linked to encephalitogenicity only in RT1.B(a)/D(a) rats. Peptides derived from the MOG sequence 91-114 were able to induce overt clinical signs of disease accompanied by demyelinated CNS lesions in the RT1.B(a)/D(a) and RT1(n) haplotypes. Notably, there was no detectable T cell response against this encephalitogenic MOG sequence in the RT1(n) haplotype in peripheral lymphoid tissue. However, CNS-infiltrating lymphoid cells displayed high IFN-gamma, TNF-alpha, and IL-4 mRNA expression suggesting a localization of peptide-specific reactivated T cells in this compartment. Despite the presence of MOG-specific T and B cell responses, no disease could be induced in resistant RT1(l) and RT1(u) haplotypes. Comparison of the number of different MOG peptides binding to MHC class II molecules from the different RT1 haplotypes suggested that susceptibility to MOG-experimental autoimmune encephalomyelitis correlated with promiscuous peptide binding to RT1.B and RT1.D molecules. This may suggest possibilities for a broader repertoire of peptide-specific T cells to participate in disease induction. We demonstrate a powerful MHC class II regulation of autoaggression in which MHC class II peptide binding and peripheral T cell immunodominance fail to predict autoantigenic peptides relevant for an autoaggressive response. Instead, target organ responses may be decisive and should be further explored.

Alleles↗

PubMed2001

Curative effects of recombinant human Interleukin-6 in DA rats with protracted relapsing experimental allergic encephalomyelitis.

We have studied the effects of treatment with recombinant human (rh)IL-6 on clinical, histological and immunological parameters of protracted relapsing (PR) experimental allergic encephalomyelitis (EAE) in DA rats. rhIL-6 (50 microg/rat subcutaneously/day) was given under three different regimens, as early prophylaxis, from 1 day prior to 14 days after immunization, in late prophylaxis, from day +7 until day 21 post-immunization (p.i.) and therapeutically to rats with clinical signs of EAE from day 14 to day 28 p.i. Although rhIL-6 failed to modulate the course of PR-EAE when administered as the early prophylactic regimen, it exerted clear-cut favourable effects on the course of the disease if was administered either as later prophylactic or as therapeutic treatment. Under these conditions, rhIL-6 accelerated recovery from EAE attacks and reduced/milded subsequent EAE episodes as compared to either PBS- or heat-inactivated rhIL-6-treated control rats. In agreement with this clinical effect, relative to PBS-treated rats, the animals injected with rhIL-6 exhibited lower numbers of MHC class II(+) and CD4(+) cells in their spinal cords. rhIL-6-treatment also profoundly modulated the endogenous cytokine network, the treated rats displaying increased numbers of spleen cells expressing mRNA transcripts of the anti-inflammatory cytokines IL-10 and TGF-beta along with simultaneously reduced numbers of mRNAs for TNF-alpha. In addition, upon ex vivo exposure to either myelin basic protein peptide 63-88 (MBP63-88) or to phytoaemagglutinin A, the numbers of IFN-gamma secreting splenocytes was also significantly reduced (ELISPOT analysis) in rhIL-6-treated rats as compared to PBS-treated controls.

Animals↗

PubMed2001

Increased glucocorticoid production and altered cortisol metabolism in women with mild to moderate Alzheimer's disease.

BACKGROUND: Abnormalities at several levels of the hypothalamic-pituitary-adrenal axis, which may promote glucocorticoid dependent neurodegeneration, have been reported in patients with Alzheimer's disease. In this study we have explored the possibility that peripheral cortisol metabolism is enhanced and glucocorticoid production is increased compensatory in patients with mild to moderate Alzheimer's disease. METHODS: Urinary excretion of cortisol and its principal conjugated metabolites was studied in ten women with mild to moderate Alzheimer's disease, seven healthy elderly women and seven young women. RESULTS: There was an age-related fall in glucocorticoid production (median, 2009 [range 1828--4201] vs. 9315 [range 3613--16,244] microg/24 hours in elderly vs. young control subjects). A-ring metabolism (i.e., the irreversible inactivation of cortisol by 5 alpha- and 5 beta-reductases) was reduced in old age. However, patients with Alzheimer's disease showed persistence of cortisol metabolite excretion. Glucocorticoid production was significantly increased in patients with Alzheimer's disease versus healthy elderly control subjects (median, 7269 [range 6005-15,335] vs. 2009 [range 1828--4201] microg/24 hours), and patients with Alzheimer's disease had increased A-ring reduction of cortisol. CONCLUSIONS: An increased glucocorticoid production is an early feature of Alzheimer's disease and may be secondary to enhanced metabolic clearance of cortisol by A-ring reduction.

Aged↗

PubMed2001

The fine specificity of the myelin oligodendrocyte glycoprotein autoantibody response in patients with multiple sclerosis and normal healthy controls.

Antibodies directed against the extracellular immunoglobulin (Ig)-like domain of the myelin oligodendrocyte glycoprotein (MOG(Igd)) mediate demyelination in experimental autoimmune encephalomyelitis (EAE) and are implicated in the immunopathogenesis of multiple sclerosis (MS). In this study we investigated the epitope specificity of MOG(Igd)-specific autoantibodies immunopurified from MS patients (n=17) and normal healthy controls (HD; n=9). ELISA, using a panel of synthetic MOG(Igd) peptides, revealed that the epitope specificity of this response was heterogeneous in both groups. The most frequently recognised epitopes were located in amino acid sequences (a.a.) 1-26 (13/17) and 63-87 (15/17) in MS patients, and 14-39 (6/9) and 63-87 (6/9) in HDs, but there was no association between MS and any particular peptide specificity. We therefore investigated the ability of the immunopurified antibodies to recognise native MOG(Igd) expressed on at the membrane surface by FACS. Unexpectedly, antibodies fulfilling this essential criterion for a demyelinating antibody response were detected only in one of the MS samples. These results indicate that the epitope specificity of the human B cell response to MOG is not only heterogeneous, but may only mediate demyelination in a limited subset of MS patients.

Adolescent↗

PubMed2001

Neurodegeneration and glial activation patterns after mechanical nerve injury are differentially regulated by non-MHC genes in congenic inbred rat strains.

Ventral root avulsion in the rat leads to a retrograde response, with activation of glia and up-regulation of immunologic cell surface molecules such as major histocompatibility complex (MHC) antigens, and the subsequent degeneration of a large proportion of the lesioned motoneurons. Herein, we examined several inbred congenic rat strains previously known to react differently to experimentally induced autoimmune diseases and demonstrate a substantial genetic diversity in the regulation of glial activation and neuron death in this injury model. The panel of examined inbred rat strains included DA(RT1AV1), PVG.1AV1, LEW.1AV1, LEW.1N, BN(RT1N) and E3(RT1U), and the following parameters were determined: (1) MHC class II expression on glia; (2) expression of glial fibrillary acidic protein, C3 complement, and microglial response factor-1 mRNAs in glia; (3) levels of the tumor necrosis factor-alpha and interleukin-1beta cytokine mRNAs; (4) degree of motoneuron loss. The findings of considerable strain-dependent differences in all parameters studied demonstrate important polymorphisms in the genetic regulation of these events. Furthermore, some of the studied features segregated from each other, suggesting independent regulatory mechanisms. Genes outside of the MHC complex are mainly implicated as being of importance for the phenotypic differences, as significant differences were recorded between the MHC congenic strains differing in the non-MHC genes but not vice versa. These results contribute new important insights into the genetic regulation of glial reactivity and neuron death after mechanical nerve injuries. In addition, the finding of conspicuous strain-dependent differences makes it necessary to consider the genetic background when designing and interpreting animal experiments involving noxious insults to the central nervous system resulting in glial activation and nerve cell loss.

Animals↗

PubMed2001

Intra-CNS activation by antigen-specific T lymphocytes in experimental autoimmune encephalomyelitis.

Identification and quantitation of autoreactive T lymphocytes is crucial in order to understand the pathogenesis of autoimmune diseases. We used flow cytometry to analyze autoantigen-specific T cellular responses in the well characterized rat experimental autoimmune encephalomyelitis (EAE) model. Cells isolated from both the central nervous system (CNS) tissue and peripheral lymph nodes were analyzed directly ex vivo or after short term in vitro culture with specific autoantigen. CNS infiltrating T lymphocytes displaying an interferon-gamma response to selected encephalitogenic myelin protein epitopes were measured kinetically during an individual disease episode and also between relapses in a chronic rat EAE model. One of the EAE models used displays a restriction towards TCRBV8S2 chain usage by the encephalitogenic T cells. In this model, in vitro production of intracellular interferon-gamma was selectively detected within this T cell subset derived from both the CNS and peripheral lymph nodes. Furthermore, antigen-specific cells infiltrating the CNS in this model produced several-fold higher amounts of interferon-gamma upon antigen stimulation and displayed a significantly increased in vivo proliferation compared with peripheral lymphocytes. These data thus directly demonstrates that T cells stimulated by a specific autoantigen in the periphery primarily acquire effector functions in the cellular environment of the target organ of the autoantigen.

Animals↗

PubMed2001

Congenic mapping confirms a locus on rat chromosome 10 conferring strong protection against myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis.

Myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in rats closely mimics the human disease multiple sclerosis (MS). As in MS, genetic predisposition to MOG-EAE is regulated by both MHC and non-MHC genes. Based on disease regulatory influences on MOG-EAE on chromosome 10 in an F2 cross between susceptible DA and resistant ACI rats, we have now isolated this locus in a congenic rat strain to enable further dissection of disease mechanisms. This region is of particular interest, since it is homologous to human 17q for which human whole-genome scans have indicated harbors genes regulating susceptibility to MS. Phenotypic comparison between DA and the congenic DA.ACI-D10Rat2-D10Rat29 strain confirms that the chromosomal segment harbors gene(s) conferring strong protection against MOG-EAE. Furthermore, resistance to EAE in this congenic strain is associated with absence or a low level of inflammation and demyelination in the central nervous system. Levels of anti-MOG antibody isotypes did not differ between parental and congenic rats, thus an action on Th1/Th2 differentiation is unlikely. In conclusion, this is the first example of an EAE-regulating locus isolated in a congenic rat strain with retained phenotype. The mechanism by which gene(s) in the region act is still unclear and will require further studies with this congenic rat strain as a tool.

Animals↗

PubMed2001

Neuroactive steroids and central nervous system disorders.

Steroid hormones are vital for the cell life and affect a number of neuroendocrine and behavioral functions. In contrast to their endocrine actions, certain steroids have been shown to rapidly alter brain excitability and to produce behavioral effects within seconds to minutes. In this article we direct attention to this issue of neuroactive steroids by outlining several aspects of current interest in the field of steroid research. Recent advances in the neurobiology of neuroactive are described along with the impact of advances on drug design for central nervous system (CNS) disorders provoked by neuroactive steriods. The theme was selected in association with the clinical aspects and therapeutical potentials of the neuroactive steroids in CNS disorders. A wide range of topics relating to the neuroactive steroids are outlined, including steroid concentrations in the brain, premenstrual syndrome, estrogen and Alzheimer's disease, side effects of oral contraceptives, mental disorder in menopause, hormone replacement therapy, Catamenial epilepsy, and neuractive steroids in epilepsy treatment.

Alzheimer Disease↗

PubMed2001

Linkage analysis in multiple sclerosis of chromosomal regions syntenic to experimental autoimmune disease loci.

Multiple sclerosis is a demyelinating disorder of the central nervous system with a putative autoimmune aetiology in which several genes are thought to be involved. Four published genomic screens have confirmed that a gene influencing MS resides within or close to the HLA class II region in 6p21. Still, this locus is likely to confer only a part of the genetic susceptibility in MS. Further, all four studies identified a number of other regions with possible linkage. We have investigated eight chromosomal intervals syntenic to loci of importance for experimental autoimmune model diseases in the rat in 74 Swedish MS families. Possible linkage (a non-parametric linkage NPL score of 1.16 by GENEHUNTER computer package) was observed with markers in 12p13.3, a region syntenic to the rat Oia2 locus which is importance for oil induced arthritis (OIA). Four markers in the T cell receptor beta chain gene region in 7q35 showed possible linkage (highest NPL score of 1.16). This locus is syntenic to the rat Cia3 locus (collagen induced arthritis). These two loci at least partially overlap with chromosomal regions showing indicative evidence for linkage in the previous MS genomic screens. Indeed, both Oia2 and Cia3 were recently found to be linked also with experimental autoimmune encephalomyelitis, a commonly used model for MS. Markers in 2p12, 3p25, 10q11.23, 17q21-25, 19q13.1, and 22q12-13 failed to provide evidence for linkage. We conclude that evidence is amounting that 12p13-12 and 7q34-36 may harbour genes with an importance for MS. The synteny with experimental loci may eventually facilitate their identification.

Alleles↗

PubMed2001

A strong association between biologically active testosterone and leptin in non-obese men and women is lost with increasing (central) adiposity.

OBJECTIVE: In both humans and rodents, males have lower levels of leptin than females at any level of adiposity. Experimental data support the idea that testosterone exerts a negative influence on leptin levels. There are, however, major inconsistencies in available data concerning the possible association between androgenicity and leptin in humans. Reasons could be the influence of androgenicity on leptin production being dependent on body composition, and incomplete measures of biologically active testosterone levels. In the present study we have characterized the relationship between biologically active testosterone and leptin after careful stratification for gender and adiposity. DESIGN AND SUBJECTS: Healthy subjects (n=158; 85 men and 73 pre- and postmenopausal women) from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) population were studied with a cross-sectional design. MEASUREMENTS: Anthropometric measurements (body mass index (BMI) and waist circumference) and oral glucose tolerance tests were performed. Circulating levels of leptin, insulin, testosterone, androstenedione, sex hormone-binding globulin (SHBG) and insulin-like growth factor-1 (IGF-1) were measured by radioimmunoassays or microparticle enzyme immunoassays. Apparent concentrations of free testosterone and non-SHBG-bound testosterone were calculated. RESULTS: After adjustments for age, BMI and insulin, leptin levels were inversely correlated to testosterone levels in non-obese men (r=-0.56, P<0.01) and obese women (r=-0.48, P<0.05). In contrast, leptin and testosterone correlated in a positive manner in non-obese women (r=0.59, P<0.01). Levels of SHBG were negatively associated with leptin in men with low waist circumference (r=-0.59, P<0.01). The following factors were associated with leptin in a multivariate model: low levels of biologically active testosterone and SHBG in men with low and medium waist circumference, insulin in men with high waist circumference, high levels of testosterone and insulin in non-obese women, and BMI in obese women. CONCLUSION: We conclude that low leptin levels are associated with androgenicity in non-obese men and women and that the direction of this association is dependent on gender and body fat distribution. Based on these results we suggest that the relation between testosterone and leptin contributes to the gender difference in circulating leptin levels. International Journal of Obesity (2001) 25, 98-105

Adipose Tissue↗

PubMed2001

Transfer of myelin-specific cells deviated in vitro towards IL-4 production ameliorates ongoing experimental allergic neuritis.

A causal role of IL-4 (Th2) production for recovery in experimental allergic neuritis (EAN) was indicated by experiments where Th1-like autoreactive cell populations, taken from the induction phase of the disease, were deviated to extensive secretion of IL-4 in a selective fashion, by ex vivo stimulation with autoantigen in the presence of IL-4. The deviated cells were adoptively transferred to EAN rats at a time just prior to the onset of clinical signs. This treatment ameliorated EAN compared with sham treatment. This therapeutic approach, with generation of autoreactive IL-4-secreting cells ex vivo followed by subsequent adoptive transfer, may become a new selective treatment of organ-specific autoimmune diseases since, in contrast to previous attempts, it is done in a physiological and technically easy way.

Adoptive Transfer↗