Neuropsychological functions,sleep, and mental health in adults with Klinefelter syndrome

A few studies have examined neuropsychological functions, sleep, and mental health combined in Klinefelter syndrome (KS; 47,XXY). We investigated neuropsychological functions with standard tests, sleep with actigraphy, and self‐reported mental health in 30 men with KS (Mean age = 36.7 years) compared to 21 controls (Mean age = 36.8 years). Men with KS scored significantly lower on mental speed, attention span, working memory, inhibition, and set‐shifting tests, as well as overall IQ (mean effect size difference Cohen's d = 0.79). Men with KS had significantly longer night wakes, with no differences in other sleep variables (mean d = 0.34). Men with KS reported poorer mental health than controls (mean d = 1.16). Regression analyses showed neuropsychological functions explained variance in some sleep domains for men with KS but not for controls. Neuropsychological functions explained variance in some mental health domains for controls. For men with KS, however, verbal IQ was the only significant predictor of mental health. Altogether, men with KS display problems in neuropsychological functions and mental health but do not appear different from controls on most sleep parameters. Our findings indicate that relations between neuropsychological functions, sleep, and mental health differ between men with KS and controls.     

New recombinants within the MHC (B-complex) of the chicken

In a search for genetic recombinations within the major histocompatibility complex (MHC) of the chicken, the B-complex, the offspring from matings between heterozygous B15/B21 and B4/B6 animals were analysed by red cell agglutination. Among the progeny, 8,912 informative typings were performed. Four recombinants were found, all separating the B-complex loci B-F and B-G (B-F codes for Class I antigens, B-G codes for an antigen of which there is no known homologue in mammals). B-L (Class II antigen) always followed B-F. Stimulation in graft versus host reactions and in mixed lymphocyte cultures followed B-F/B-L. The mapping distance between the two loci B-F and B-G is in the range of 0.04 centimorgan. The lack of recombinants separating individual B-F loci in this study and in the studies of others might indicate that chicken MHC is less complex than those of mammalian species, but alternative explanations are also possible. So far no serologically defined recombinant separating Class I (B-F) and Class II (B-L) loci has been found.     

Expression and synthesis of fibroblast growth factor-9 in human gammadelta T-lymphocytes. Response to isopentenyl pyrophosphate and TGF-beta1/IL-15

Gammadelta T-lymphocytes are believed to play a role in maintaining the normal configuration of epithelial tissue. As little is known about the factors mediating this function, we addressed the question of whether gammadelta T-lymphocytes produce fibroblast growth factor (FGF)-9 as well as two other growth factors associated with epithelial tissue reconstitution. Blood gammadelta T cells isolated from healthy donors were grown in the presence of isopentenyl pyrophosphate (IPP) or transforming growth factor-beta1 (TGF-beta1)/interleukin-15 (IL-15) for 24 h and were assessed for the expression and synthesis of FGF-9, keratinocyte growth factor (KGF), and epidermal growth factor (EGF). Resting human gammadelta T cells constitutively expressed KGF and FGF-9 mRNA but no EGF mRNA. In the presence of IPP, FGF-9 mRNA expression significantly increased in a dose-dependent manner, expression of KGF remained unaltered, and EGF mRNA could not be detected. In contrast to IPP, stimulation of the cells with TGF-beta1/IL-15 did not alter FGF-9 expression. Moreover, stimulation with anti-CD3 does not induce FGF-9 expression but triggers a high signal of interferon-gamma mRNA. Western blot analysis of gammadelta T cell lysates, prepared 4 days following stimulation with IPP, showed an increase of FGF-9 protein as compared with control cells. In conclusion, the results demonstrate for the first time that human blood and bronchoalveolar lavage gammadelta T-lymphocytes are capable of expressing FGF-9. The data also provide novel evidence that immunoregulatory cells can synthesize FGF-9.     

Inhibition of endogenous carcinoembryonic antigen (CEA) increases the apoptotic rate of colon cancer cells and inhibits metastatic tumor growth

It has been suggested that carcinoembryonic antigen (CEA) enhances metastatic seeding of colon cancer cells due to its homo- and heterophilic binding properties. Our recent finding that endogenous CEA protects colon cancer cells against apoptosis suggests a more complex role of CEA in cancer progression. In this study we compared the in vitro effects of endogenous CEA on tumor cell aggregation and cell cycle regulation of human HT29 colon cancer cells with the corresponding in vivo effects, i.e. tumor cell seeding and formation of metastatic lesions. Stable expression of CEA targeted ribozymes (Rz) under control of a tet-off promoter system allowed regulation of CEA levels on the mRNA and protein level by 50%. Downregulation of CEA levels inhibited tumor cell aggregation by 70%. In accordance with previous studies [1], reduction of CEA levels increased in vitro the apoptotic rate and reduced colony formation by 30% to 50%. To determine the in vivo effect of CEA-dependent aggregate formation and its growth regulating role under apoptotic stress, HT29 cells with high and low CEA levels, respectively, were injected into nude mice. Immunostaining of lung microsections revealed similar numbers of tumor cells one hour after injection. 24 h later virtually all cells were removed from the lung in both groups. However, after 6 weeks all doxycycline treated mice (Rz off = CEA high) showed 14.5 ± 4.6 metastatic lung lesions/mouse while 0.2 ± 0.2 lesions/mouse appeared in the untreated group (Rz on = CEA low) ( P<0.001). Our study demonstrates a multifunctional role of CEA and indicates a prometastatic role of CEA independent of its adhesive function possibly due to its anti-apoptotic function. This revised version was published online in July 2006 with corrections to the Cover Date.     

Analysis of chickens for recombination within the MHC (B-complex)

In an attempt to further map the chicken MHC (the B complex), a systematic search for genetic recombinants within the B complex was performed by serotyping the progeny from F2 crosses of chickens by means of specific anti-class I, anti-class II, and anti-class IV alloantisera. Two recombinant B-haplotypes (B21r and B15r) were found by analysing 2,656 F2 chickens representing 5,312 informative typings. In either case, the B-G (class IV) allele was recombined with both the B-F and B-L alleles of the opposite haplotype. MLC typings, tests for direct compatibility by GVH reactions, and absorption analyses confirmed the original serological typing of the two recombinant B haplotypes. No recombination between B-F (class I) and B-L (class II) loci was found. This very low frequency of recombination within the B complex as compared with recombination frequencies found in mammalian MHC's is discussed.     

Genomic approach to identification of Mycobacterium bovis diagnostic antigens in cattle

Differential delayed-type hypersensitivity skin testing with tuberculin purified protein derivatives from Mycobacterium bovis and M. avium is the standard for diagnosing bovine tuberculosis. However, improved tests based on defined, specific antigens are urgently needed. In the present study, a combination of bioinformatics, molecular biology, and bovine models of infection were used to screen mycobacterial proteins for their potential as diagnostic reagents which could be used in a whole-blood assay for diagnosis of tuberculosis. Initial screening of 28 proteins selected in silico and expressed as recombinants in Escherichia coli indicated that CFP-10, ESAT-6, TB27.4, TB16.2, TB15.8, and TB10.4 induced strong gamma interferon responses in experimentally infected cattle. A more thorough investigation over time in two groups of animals infected with a high (10(6) CFU) and a low (10(4) CFU) dose of M. bovis revealed that, for both groups, the strength of the in vitro response to individual antigens varied greatly over time. However, combining the results for ESAT-6, CFP-10, and TB27.4, possibly supplemented with TB10.4, gave sensitivities at different infection stages close to those obtained with M. bovis purified protein derivative. Importantly, while responsiveness to ESAT-6 and CFP-10 correlated strongly for individual samples, the same was not the case for ESAT-6 and TB27.4 responsiveness. The results suggest that combinations of specific antigens such as these have great potential in development of optimized diagnostic systems for bovine tuberculosis.     

Inhibition of anti-GD3-ganglioside antibody-induced proliferation of human CD8+ T cells by CD16+ natural killer cells

The ganglioside GD3 has been described as a membrane component of human T cells which is involved in T cell growth. In the present study the activating function of GD3 for human CD4⁺ and CD8⁺ T cells was analyzed by five different monoclonal antibodies (mAb) directed against the GD3 molecule. Three mAb U5, Z21 and R24 induced strong proliferation of peripheral blood mononuclear cells and purified CD8⁺ and CD4⁺ T cells of normal donors containing less than 5% CD16⁺ natural killer (NK) cells. In contrast to CD4⁺ T cells, CD8⁺ T cells proliferated only weakly in the presence of 15% CD16⁺ NK cells. The proliferative response of purified CD4⁺ and CD8⁺ T cells (<5% NK cells) correlated with the antibody-dependent induction of integral and soluble interleukin-2 (IL-2) receptors and was reduced to 20% by an anti-IL-2 receptor antibody. Our results show, that the GD3 molecule represents an activation molecule for both CD4⁺ and CD8⁺ T cells and that CD16⁺ NK cells selectively inhibit anti-GD3 antibody-induced proliferation of CD8⁺ T cells.