Increased activation and oligoclonality of peripheral CD8(+) T cells in the chronic human helminth infection alveolar echinococcosis

Alveolar echinococcosis (AE) in humans is a chronic disease characterized by slowly expanding liver lesions. Cellular immunity restricts the spreading of the extracellular pathogen, but functional contributions of CD4(+) and CD8(+) T cells are not defined. Here we studied ex vivo the phenotype and function of circulating T-cell subsets in AE patients by means of flow cytometry, T-cell receptor spectratyping, and lymphocyte proliferation. AE patients with parasitic lesions displayed a significant increase of activation of predominantly CD8(+) T cells compared to healthy controls and AE patients without lesions. In vitro, proliferative T-cell responses to polyclonal stimulation with recall antigens and Echinococcus multilocularis vesicular fluid antigen were sustained during chronic persisting infection in all AE patients. Only in AE patients with parasitic lesions did T-cell receptor spectratyping reveal increased oligoclonality of CD8(+) but not CD4(+) T cells, suggesting a persistent antigenic drive for CD8(+) T cells with subsequent proliferation of selected clonotypes. Thus, our data provide strong evidence for an active role of CD8(+) T cells in AE.     

Epidemiological and clinical features of travel-associated cryptosporidiosis

Data concerning the clinical and epidemiological features of travel-associated cryptosporidiosis are lacking. In order to investigate the impact of this disease on travellers' health, a retrospective study was conducted at the Institute of Tropical Medicine, Berlin. In total, 57 cryptosporidial infections were identified between 2000 and 2004, resulting in a prevalence of 2.9% in patients with travel-associated diarrhoea. Travel to south-central Asia, especially India, was associated with a higher prevalence of infection than was travel to other destinations. Clinically, the disease resembled giardiasis, but fever and arthralgias seemed to occur more frequently.     

A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin

Histone lysine methylation is a central modification to mark functionally distinct chromatin regions. In particular, H3-K9 trimethylation has emerged as a hallmark of pericentric heterochromatin in mammals. Here we show that H4-K20 trimethylation is also focally enriched at pericentric heterochromatin. Intriguingly, H3-K9 trimethylation by the Suv39h HMTases is required for the induction of H4-K20 trimethylation, although the H4 Lys 20 position is not an intrinsic substrate for these enzymes. By using a candidate approach, we identified Suv4-20h1 and Suv4-20h2 as two novel SET domain HMTases that localize to pericentric heterochromatin and specifically act as nucleosomal H4-K20 trimethylating enzymes. Interaction of the Suv4-20h enzymes with HP1 isoforms suggests a sequential mechanism to establish H3-K9 and H4-K20 trimethylation at pericentric heterochromatin. Heterochromatic H4-K20 trimethylation is evolutionarily conserved, and in Drosophila, the Suv4-20 homolog is a novel PEV modifier to regulate position-effect variegation. Together, our data indicate a function for H4-K20 trimethylation in gene silencing and further suggest H3-K9 and H4-K20 trimethylation as important components of a repressive pathway that can index pericentric heterochromatin.     

Pleiotropic effect of the TPH A779C polymorphism on nicotine dependence and personality.

Recent studies from molecular genetics have suggested an association between the tryptophan hydroxylase 1 (TPH1) gene and nicotine addiction indicating a dysfunction of the serotonergic (5-HT) system in smoking behavior. In a sample of 252 healthy subjects, a significant association between variations observed in nicotine dependence and the heterozygous AC-genotype of the TPH A779C polymorphism could be demonstrated. Moreover, the heterozygous genotype was significantly associated with a personality trait of neurotic aggression (indirect hostility, negativism), as measured by the Buss-Durkee-Hostility-Inventory (BDHI). The positive heterosis effects with respect to nicotine addiction and personality support the idea that the TPH1 gene exerts pleiotropic effects.     

Nachweis von α-Mannosidase und β-Glucosidase in einem für die Hefezellwand lytischen System von Streptomyces spec. 5s

Streptomyces spec. 5s accumulates in the culture fluid lytic activities against living cells of Candida guilliermondii H. From the culture fluid a freeze-dried dialyzed ammonium sulfate precipitate was prepared. Except β-glucosidase-activity it showed activity of α-mannosidase which was characterized. Separation of both enzymes by chromatography on polyacrylamide gel was possible.     

Über polymere Alloxazine, 2

A new synthesis for 7-vinylalloxazine ( 4 ) was developed. It was neither polymerizable in DMSO nor in DMF. Poly(7-vinylalloxazine) ( 7 ) was obtained by polymer-analogous reactions starting from poly(4-aminostyrene). Its ability to form complexes with Ag⁺-und Hg²⁺-ions was investigated.     

Magnetophosphenes: a quantitative analysis of thresholds

Low-frequency and transient magnetic fields of moderate flux densities are known to generate visual phenomena, so-called magnetophosphenes. In the present study, time-variable very low frequency (10–50 Hz) electromagnetic fields of moderate flux density (0–40 mT) were used to induce magnetophosphenes. The threshold values for these phosphenes were determined as a function of the frequency of the magnetic field both in normal subjects and colour defective ones. Maximum sensitivity occurred at a frequency of approximately 20–30 Hz, and with broad-spectrum light the threshold flux density was 10–12 mT. The threshola values were found to be dependent upon the intensity and the spectral distribution of the background light. Sensitivity decreased during dark adaptation. In certain respects deutans differed from subjects with normal colour vision. Possible mechanisms for generation of magnetophosphenes are discussed. The present magnetic threshold curves show a close resemblance to corresponding curves obtained by electric stimulation at various frequencies provided the electric thresholds are divided by the a.c. frequency. These problems are under current investigation in our laboratory. This is in full agreement with the assumption that the fluctuating magnetic field affects retinal neurons by inducing currents which polarise synaptic terminals.     

Impeded Th1 CD4 memory T cell generation in chronic-persisting liver infection with Echinococcus multilocularis

Memory T cells of the CD4 lineage coordinate immune responses against pathogens via the antigen-induced secretion of potent effector cytokines. The efficacy of these responses is thought to depend on both the overall number of pathogen-specific memory T cells and the particular array of cytokines that these cells are programmed to secrete. It is unknown to what extent cellular immunity can be induced by Echinococcus multilocularis infection. To examine the immunological memory provided by the adaptive cellular immune system in control of the chronic-persisting infection, peripheral lymphocytes of patients with alveolar echinococcosis (AE) were studied ex vivo. Stimulation of memory cells was performed with E. multilocularis vesicular fluid, purified protein derivative as recall antigen and phytohemagglutinin. Cytomegalovirus latency served as disease control. Frequencies of circulating CD4(+) T cells secreting IFN-gamma, IL-2, tumor necrosis factor-alpha, IL-4, IL-5 and IL-10 were determined by both cytokine flow cytometry and ELISPOT assays. Most strikingly, in chronic AE the frequencies of E. multilocularis antigen-specific cells committed to T(h)1-cytokine production were low (mean 0.5% of CD4(+) T cells). However, an E. multilocularis-specific response of CD4(+) T cells at frequencies of >/=0.1% was detected in the majority of AE patients (68%). Low numbers of cells committed to T(h)1 cytokine secretion were invariably seen in patients with active and inactive disease. Interestingly, the number of specific CD4(+) memory T cells was not increased in cured AE patients after complete surgical removal of the metacestode. Hyporesponsiveness during the chronic helminth infection was E. multilocularis specific. Thus, our results demonstrate that antigen-specific memory function against E. multilocularis is markedly different from that against viral or bacterial pathogens. Whether the antigen-specific cellular hyporesponsiveness with impeded T(h)1 CD4(+) memory T cell generation is a cause or a result of the progressive metacestode activity remains to be determined.     

Drug-Resistant Tuberculosis in Pet Ring-Tailed Lemur,Madagascar

We diagnosed tuberculosis in an illegally wild-captured pet ring-tailed lemur manifesting lethargy, anorexia, and cervical lymphadenopathy. Whole-genome sequencing confirmed the Mycobacterium tuberculosis isolate belonged to lineage 3 and harbored streptomycin resistance. We recommend reverse zoonosis prevention and determination of whether lemurs are able to maintain M. tuberculosis infection.