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  • 1
    ISSN: 1432-0428
    Keywords: Keywords Leptin ; leptin receptor ; Ob-R ; obesity ; sequence variant.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Leptin is an adipocyte-derived blood-borne satiety factor that acts on its cognate leptin receptor (Ob-R) in the hypothalamus, thereby regulating food intake and energy expenditure. To explore whether mutations in the Ob-R gene cause obesity in humans, we have searched for mutations in the gene for Ob-Rb, a biologically active receptor isoform, in obese Japanese subjects. We have also examined associations between such mutants and obesity in the Japanese. Genomic DNAs were used as templates in polymerase chain reaction (PCR) with primers selected to amplify exons 2 to 20 of the human Ob-Rb gene. Direct sequence analysis of the PCR products revealed 7 nucleotide sequence variants (Lys109Arg, Gln223Arg, Ser343Ser, Ser492Thr, Lys656Asn, Ala976Asp, and Pro1019Pro) in the Ob-Rb coding region from 17 obese Japanese subjects with a family history of obesity (BMI 39.3 ± 8.4 kg/m2). No missense and nonsense mutations were found such as those in Zucker fatty (fa/fa) rats and Koletsky (fa k /fa k) rats. Nucleotide substitutions occurred at relatively high frequencies at codons 109, 223, 976, and 1019 (79, 91, 100, and 85 %, respectively). Allele frequency of each variant determined by PCR-RFLP and PCR-single strand conformation polymorphism analyses showed no significant differences between 47 obese (BMI 35.1 ± 6.5 kg/m2) and 68 non-obese (BMI 21.6 ± 2.2 kg/m2) subjects. The present study represents the first report of sequence variants of the Ob-Rb gene in the Japanese and provides evidence against either obesity-causing mutations or association of sequence variants with obesity in obese Japanese subjects. [Diabetologia (1997) 40: 1204–1210]
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 152 (1993), S. 647-649 
    ISSN: 1432-1076
    Keywords: Interleukin 6 ; Kawasaki disease ; Renal involvement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Kawasaki disease (KD) often presents with abnormal urinary findings, such as aseptic pyuria, mild proteinuria and microscopic haematuria. In this study, we measured urinary interleukin-6 (IL-6) by a sensitive sandwich ELISA assay using mouse monoclonal antibodies against recombinant IL-6 to elucidate the role of IL-6 in the pathogenesis of renal lesions in KD. Serum IL-6 levels were increased in acute KD as well as in febrile controls. Importantly, urinary IL-6 levels were consistently elevated in patients with acute KD, but much lower in febrile controls. Urinary IL-6 levels returned steadily to normal during the convalescent phase. In addition to IL-6, urinary levels ofN-acetyl-β-d-glucosaminidase (NAG) and β2-microglobulin (β2-mg) were also elevated during the acute phase of this disease. Eosinophils and macrophages were identifiable in urinary sediments from these patients. The increased levels of urinary IL-6 in combination with increased NAG and β2-mg seemed to suggest the presence of certain renal parenchymal lesions with cellular infiltration during the acute phase of the disease. IL-6 may serve as clinically useful parameter for the detection and monitoring of the renal involvement in KD.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background The T helper type-2 (Th2)-dominated situation can be observed in allergic diseases such as asthma or atopic dermatitis. A reduced ability to produce IL-12, which is a key cytokine for the induction of Th1 responses, has been proposed to lead to aberrant Th2 development in these disease conditions.Objective This study was intended to examine how IL-12-producing ability might associate with allergic diseases as a function of age.Methods IL-12 production by monocytes at various ages was assessed in patients with bronchial asthma and/or atopic dermatitis (n = 100) in comparison with non-allergic control subjects (n = 144). Whole blood cells were stimulated with lipopolysaccharide (LPS) after priming with IFN-γ, then intracellular cytokine expression of IL-12 and IL-8 as a control cytokine of CD14-positive cells was assessed by flow cytometric analysis.Results In the control subjects, the ability of monocytes to produce IL-12 was negligible at birth and gradually increased with advancing age, whereas IL-8 production was intense throughout the human life. At more than 7 years of age, IL-12 production of patients with allergic diseases was significantly lower compared with that of control subjects. The unexpected finding was that infants and children below 6 years of age with allergic diseases tended to produce more IL-12 compared with age-matched controls. In this young group, it was noted that enhanced IL-12 production by monocytes was especially observed in allergic patients with specific IgE antibodies against some food allergens. Significant inverse relationships between serum IgE levels and IL-12-producing ability were found in the teenage and adult groups, but not in the younger children.Conclusion IL-12 appeared to play different roles in the pathogenesis of allergic diseases between younger and older ages.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 35 (1992), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Reconstitution of severe combined immunodeficient (SCID) mice with human lymphocytes has recently allowed the elucidation of abnormalities of immune responses in various immunological disorders. In the present study, mononuclear cells (MNC) from neonatal cord blood and adult peripheral blood were intraperitoneally injected into SCID mice to examine induction of human Ig in respective mice recipients. Human IgG was consistently detected in the serum of SCID transferred with adult MNC, but only a few SCID recipients of cord blood MNC showed detectable but low levels of IgG in the serum. The combination experiments of isolated B and T cells disclosed that some interactions between B and T cells might be necessary for IgG production in transferred SCID mice. Notably, transfer of cord blood B cells with adult but not cord blood T cells resulted in efficient induction of IgG, associated with a change in subclass distribution. The results suggest that inability of neonatal B cells to produce IgG can be overcome by transfer with adult mature T cells into SCID mice.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 8 (1978), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In tuberculin-sensitive individuals, IgG Fc receptor (FcR)-hearing lymphocytes in the peripheral blood increased transiently following PPD-tuberculin skin test. This rise in circulating FcR-bearing cells appeared to peak about 36–48 h after the intradermal inoculation of PPD and seemed to occur largely in the T cell population. Skin test-negative individuals showed no significant changes in their circulating FcR-bearing cells following PPD inoculation. Peripheral blood lymphocytes from PPD-sensitive individuals were fractionated into non-T cell and T cell-enriched populations by E rosette sedimentation technique. FcR-bearing cells in the T cell-enriched population were eliminated by EA rosette sedimentation: i. e. FcR-negative T cells. Then, equal numbers (1 × 105 cells each) of non-T cells and unfractionated or FcR-negative T cells were recombined in culture. Prior to PPD inoculation, there was no significant difference between these two cell mixtures in the in vitro cellular response to PPD or mitogens. When these cell populations were obtained. 16–48 h after PPD inoculation, however, the combination of non-T tells and FcR-negative T cells responded to PPD much better than the combination of non-T cells and unfractionated T cells, whereas the mitogen-induced cellular proliferation of these two cell mixtures did not differ from each other.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A male infant with partial DiGeorge syndrome responded to weekly administration of levamisole (2.5 mg/kg of body weight) with an increase of circulating E-rosette-forming T cells. Thymic hormone activity in plasma appeared to be elevated to a near-normal level of 11.6 ng thymopoietin equivalent/ml after levamisole administration. The in vitro incubation studies indicated that levamisole by itself had no E-rosette-promoting ability, but a dialysable and relatively heat-stable plasma factor induced by levamisole both in the patient and in heallhy individuals had E-rosette-promoting activity for the patient's lymphocytes. Such a plasma factor, however, could not be induced in all four thymectomized myasthenic subjects examined, suggesting a thymus-dependent nature of the plasma factor. These results suggest that levamisole might mediate an increased secretion of humoral factor(s) with E-rosette-promoting activity, even from such a rudimentary thymus as in the partial DiGeorge syndrome.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Th2 clones have been reported to express CD30 preferentially, but whether T cells producing Th2-type cytokines may favor CD30 expression in the in vivo state remains unknown. We investigated the expression of CD30 on circulating T cells in atopic dermatitis (AD) as a Th2-dominated disorder. Peripheral blood mononuclear cells were prepared from 51 AD patients and 14 nonatopic controls, and their phenotypes were analyzed with flow cytometry. Cytokine production by stimulated CD4+ T cells was also assessed by the single-cell-staining method. Flow cytometric analysis clearly revealed that CD30+ T cells were identifiable in the blood of AD patients with greater frequency compared to controls. The important finding was that CD30 expression was restricted to a small but substantial population of memory (CD45RO+) CD4+ T cells, but not CD8+ ones. In AD patients, it was demonstrated that the percentages of CD30+ cells within CD45RO+ CD4+ T cells correlated well with the disease severity, serum IgE levels, peripheral eosinophil counts, and tendency toward Th2-dominant cytokine pattern as determined by the ratio of interleukin-4 to interferon-gamma production. This study suggests that CD30 expression in circulating T cells might serve as an in vivo marker for the Th2-dominated condition.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Allergy 56 (2001), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Although the association between acute asthma exacerbation and viral infection has been well documented, virus identification rates vary. It has recently been reported that the expression of MxA protein in lymphocytes, inducible by type I interferons, can serve as a sensitive marker for viral infection in the host. The objective was to determine the contribution of viral infection to precipitation of asthma attacks in children. Methods: We studied 186 asthmatic children, aged 0–12 years, over a 1-year period to evaluate MxA protein levels in peripheral blood lymphocytes by using a flow cytometric analysis in whole blood. Results: Of all the subjects, 80 (47%) exhibited significantly elevated levels of MxA expression in lymphocytes, presumably indicating the states of viral infection. The association of viral infections with acute asthma exacerbation seemed to be marked in younger children: enhanced MxA expression was seen in 73.3% of infants (aged 0–1 year), 49.5% of toddlers (aged 2–5 years), and 26% of schoolchildren (aged 6–12 years). Seasonal changes in the frequency of viral infection associated with deterioration were also observed. Conclusions: Flow cytometric assay of MxA protein expression in whole blood appears to be an easy and useful method to evaluate viral infections in acute asthma exacerbation.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A single oral dose of 150 mg levamisole was administered to five healthy adults. Circulating Fc(IgG) receptor-bearing T cells (Tγ cells) increased for 5 days after levamisole intake, but total E rosette-forming cells showed no significant alterations. The generation of immunoglobulin-producing cells in the peripheral blood lymphocytes (PBL), which was induced in the in vitro pokeweed mitogen (PWM)-stimulated cultures, was significantly suppressed for 5 days after levamisole administration. Suppressor T-cell activity on B-cell differentiation, which was induced by levamisole intake, was evaluated by co-culturing with allogeneic untreated adult PBL in the PWM system in six other volunteers. A seemingly dose-dependent suppression on B-cell differentiation was exerted by T cells isolated on day 3 of levamisole treatment, but not by T cells which were isolated before or on day 14 of the experiment. When T cells were fractionated into two subsets with regard to the presence or absence of Fc(IgG) receptors, suppressor T-cell activity appeared to be generated by levamisole largely in T cells lacking Fc(IgG) receptors, but not in Tγ cells.
    Type of Medium: Electronic Resource
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