Identification of a novel allele: DQB1*06:127 in Hispanic sisters.

Newly identified allele, HLA-DQB1*06:127, differs from DQB1*06:02:01 by the single nucleotide substitution 426C-A at codon 110 in exon 3.

[Functional magnetic resonance imaging of psychopharmacological brain effects: an update]. / Funktionelle Kernspintomographie (fMRI) und Psychopharmakaeffekte: Eine Standortbestimmung.

Functional magnetic resonance imaging (fMRI) is well established for the examination of functional activity in the living brain. The method permits the development of functional activation maps during perceptual, cognitive and emotional efforts with a high temporal and spatial resolution. As of late there has been growing interest in using this technique to investigate regionally specific brain activity following the administration of drugs such as nicotine, cocaine, lorazepam, scopolamine, antipsychotics or antidepressants. Studies in experimental animals investigate signal changes associated with the administration of psychopharmacological substances in different brain areas using a high magnetising field (> 4 Tesla). FMRI-studies in healthy human volunteers and psychiatric patients focus on cerebral activity following acute drug administration (single challenge) and on adaptive effects of the CNS due to long- term medication. Their results provide insights into brain physiology and neuropharmacological mechanisms which are in turn relevant for preclinical pharmacological studies, responder analyses and for the investigation of pathogenetic models in psychiatric diseases. However, with these new opportunities, additional methodological considerations and limitations emerge. Besides the need of controlling motion artefacts, the influence of interfering psychological variables, an exact specification of the experimental design, a standardised analysis for data adjustment and technical limitations have to be considered. This article provides an overview of the underlying model of brain function, present applications, future possibilities and methodological limitations of fMRI for the understanding of human psychopharmacology.

[Augmentation of selective serotonin reuptake inhibitors (SSRI) with atypical antipsychotics in the treatment of depression]. / Augmentation von selektiven Serotonin-Wiederaufnahme-Hemmern (SSRI) mit atypischen Antipsychotika in der Depressionsbehandlung.

The treatment of severe depression represents a difficult task in the daily psychiatric practice. In certain cases, augmentation therapies in order to improve the efficacy of SSRIs can be useful. Recently, it has become possible to use atypical antipsychotics for SSRI augmentation. This option adds to the existing strategies in the treatment of depression and primary systematic studies show encouraging results. In this review, the possibility of a SSRI augmentation by additionally administering risperidone or olanzapine is critically discussed.

The antisense oligonucleotide ISIS 2922 prevents cytomegalovirus-induced upregulation of IL-8 and ICAM-1 in cultured human fibroblasts.

Human cytomegalovirus (HCMV) infection is associated with excessive proinflammatory immune responses such as cytokine/chemokine production or upregulation of adhesion molecules on the host cells. It is assumed that these features of HCMV-related immunopathology can not be treated effectively with currently available anti HCMV drugs. In the present study the efficacy of ganciclovir (GCV), foscarnet (PFA), cidofovir (HPMPC), and ISIS 2922, an antisense oligonucleotide complementary to HCMV immediate-early (IE) mRNA, was investigated on HCMV-induced secretion and functional activity of the C-X-C chemokine IL-8 and the expression of the intercellular adhesion molecule-1 (ICAM-1). As compared with mock-infected cells IL-8 production was increased up to 9-fold and ICAM-1 expression up to 4-fold in HCMV-infected fibroblasts. Treatment of infected cells with GCV (40 microM), PFA (200 microM) or HPMPC (2 microM) suppressed completely virus replication as demonstrated by quantification of late (L) antigen expression and infectious virus production. These drugs, however, failed to inhibit IE antigen expression and did not prevent HCMV-induced upregulation of IL-8 and ICAM-1. In contrast, ISIS 2922 (1 microM) suppressed both IE and L antigen expression by 99% and inhibited infectious virus production by 10(4)-fold. Moreover, ISIS 2922 significantly suppressed HCMV-induced upregulation of both IL-8 and ICAM-1 expression on the transcriptional and on the protein level. Our results indicate that ISIS 2922 but not inhibitors of HCMV DNA prevents HCMV-induced upregulation of IL-8 and ICAM-1, both hallmarks of inflammatory processes. Thus, inhibition of HCMV IE expression with ISIS 2922 may be an important strategy for the treatment of HCMV-related immunopathogenesis.

[[In vitro culture of iris cells]. / Kultivierung von Iriszellen in vitro.

BACKGROUND: The biological behaviour of iris cells in vitro was not yet completely investigated. For a more detailed study of the scope of cultivation of iris cells in vitro we isolated human iris pigment epithelium (IPE) cells and iris fibroblasts. MATERIALS AND METHODS: For the purpose of this study iris cells were isolated from 19 donor eyes. A method was established for isolation and cultivation of IPE cells by means of fibronectin coating and the use of a special cell culture medium. Additionally, a method was developed for the selection of fibroblasts from iris stroma (IS) in vitro by means of fibronectin coating, passaging and proliferation in cell culture medium. RESULTS: The IPE and IS cells could be cultivated successfully. The IPE cells started to divide after a mean interval of 5.4 +/- 0.7 days in culture. The mitosis of IS cells was observed after 3.3 +/- 0.87 days in culture. Confluency of IPE cells was reached after 14.7 +/- 4.92 days and by IS cells after 8.1 +/- 1.45 days. Immunocytochemical staining using two antibodies for cytoceratin and one for human fibroblast showed that the IPE cell culture was pure and that the IS culture consisted of fibroblasts. Furthermore, electron microscopy of IPE and IS cultures confirmed the results of the immunocytochemical staining. CONCLUSIONS: The use of human IS and IPE cells in vitro has established a novel model for the research on iris cells. The model might possibly be applied in the research of metabolic structures and diseases of the iris.

[Depressive reactions and psychological processing of HIV-positive homosexual males]. / Depressive Reaktionen und psychische Verarbeitung bei HIV-positiven homosexuellen Männern.

Interviews and psychotherapeutic treatments performed with HIV-positive males reveal frequent depressive crises in some of the men, whereas others are mentally relatively stable after having gone through a period of mourning over the loss of long-term life perspectives and prospects. The present study examined in 54 HIV-positive male homosexuals not suffering from AIDS, the causes of the depressive management by comparing a depressive and a non-depressive group. The results show: 1. that three well-defined styles of coping can be discerned, namely, "self-confrontation", "avoidance", and "seeking social support"; 2. that the "avoidance" style of coping is particularly pronounced in the depressive group; 3. that in 86% of the depressive but only in 26% of the non-depressives there is a noticeable conflict between socioemotional retreat and seeking social support; 4. that the depressives estimate the changes of any subjective influence on the course, as being very low, whereas the subjective probability of falling ill is correspondingly high, the self-confronting coping style correlating negatively with the subjective disease probability; 5. that in the depressive group the reasons for the infection are seen rather in one's own person, a mental predisposition being held co-responsible. In this context, the lower self-acceptance of one's own homosexuality plays a decisive role in the "subjective infection theory".

[HIV infection: trauma and coping with trauma]. / HIV-Infektion: Trauma und Traumaverarbeitung.

The initial results of a German-Swedish research project demonstrate the at times active-resistant and at times passive-resigned approaches of AIDS patients toward their illness.

Left-handed Z-DNA in bands of acid-fixed polytene chromosomes.

Antibodies to DNA in the left-handed (Z) conformation bind to acid-fixed polytene chromosomes of both Chironomus thummi and Drosophila melanogaster, as shown by direct and indirect immunofluorescence. Comparison of the phase-contrast, immunofluorescence, and DNA staining patterns shows a predominant localization of the antibody to the regions of high contrast and DNA density, the bands. The immunofluorescence is completely abolished by competition with polynucleotides in the Z conformation but not by those in the B form. DNase but not RNase treatment eliminates the antibody staining. Actinomycin D inhibits binding, whereas mithramycin has no effect. The highly reproducible immunofluorescence patterns obtained with the anti-Z-DNA antibodies demonstrate variations in fluorescence intensity between particular bands, which can be quantitated by laser scanning and photon counting techniques. The telomeric regions and DNA strands associated with end-to-end chromosome linkage and ectopic pairing are exceptionally bright. At saturation, average values of 1 IgG molecule per 3,000 base pairs and 1 per 15,000 base pairs are found in the intensely and weakly staining regions, respectively. An alternative statement is that the left-handed Z-DNA conformation is present at a frequency of 0.02-0.1%. The measured differences reflect variations in the local density of Z-DNA sites and not in the affinity for the specific antibody, which appears to be relatively constant throughout the chromosomes (Kd approximately equal to 10 nM). These observations taken together with results of biophysical studies on the properties of Z-DNA in solution suggest that regions of DNA in the left-handed conformation could be involved in higher-order structural organization of chromosomes and possibly in modulation of their functional state.

Information coding in the visual system: a new hypothesis.

Experiments on subjective color sensations using a special signal generator and a standard TV monitor (black and white) led to a new hypothesis on information coding in the visual system. According to this hypothesis a trigger signal is required which restores the phase correlation of the pulse-coded spiking of the neurons transmitting visual information from the eye to the brain. The "shift effect" ("periphery effect"), either artificially induced or initiated by microsaccades, might act as the postulated trigger.