Autoantibody reactivity in serum of patients with major depression, schizophrenia and healthy controls.

The present study assessed 25 patients with unipolar major depression and 34 patients with schizophrenia along with 50 healthy, non-psychiatric controls for the presence of serum antinuclear (ANA), smooth muscle (SMA), anti-endothelial (AEA), anti-sarcolemma (ASA), thyroid gland (TGA) and parietal cell (PCA) antibodies. In the group of patients with major depression, the frequency of elevated ANA, TGA and PCA was significantly higher than in the control group. In addition, the group of patients with schizophrenia significantly more often showed increased levels of ANA and SMA than the control group of healthy volunteers. When the two psychiatric groups were compared, PCA serum titers in major depression and SMA values in schizophrenia were significantly more frequently elevated, whereas values of AEA and ASA showed no difference. These results point towards the existence of an unspecific (auto) immune disposition or reaction in at least a subgroup of patients with major depression and schizophrenia.

Altered lymphocyte distribution in Alzheimer's disease.

The contribution of immunological factors in the etiopathogenesis of Alzheimer's disease (AD) is increasingly noted. Apart from cerebral immunological findings, peripheral changes of the immune systems have been reported including lymphocyte function and subset distribution. As data still remain inconsistent, we investigated a sample of 43 patients with AD and of 34 healthy age-matched controls. Distribution of the T-, B- and NK cell subsets was determined by flow cytometry (FACS). We found a significant decrease of CD3(+) lymphocytes as well as of CD19(+) lymphocytes. A slight increase of the CD4(+) and a decrease of the CD8(+) subpopulation could be observed, without significant change of the CD4(+)/CD8(+) ratio. CD16(+)56(+) cells were not altered. Our findings of decreased T- and B-Cell numbers in AD sustain the hypothesis of a general decline of immune activity in AD. A putative association with premature immunosenescence in AD and possible pathogenetic implications are discussed.

BDNF serum and CSF concentrations in Alzheimer's disease, normal pressure hydrocephalus and healthy controls.

Alzheimer's disease (AD) and normal pressure hydrocephalus (NPH) are common forms of dementia in the elderly. Recent findings have suggested an involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of AD. BDNF is an endogenous protein involved in the maintenance of neuronal function, synaptic plasticity and structural integrity in the adult brain. BDNF serum and cerebrospinal fluid (CSF) concentrations were assessed by a sensitive ELISA in 27 AD patients in comparison to 9 NPH patients and 28 age-matched healthy controls (10 CSF samples). We found a significant decrease of BDNF serum concentration in AD (18.6ng/ml) and NPH patients (18.1ng/ml) as compared to healthy controls (21.3ng/ml; p=0.041/p=0.017). BDNF serum concentrations did not correlate with CSF levels, age or MMSE scores both in AD and NPH patients. In unconcentrated CSF samples, BDNF could be detected in AD patients in 8/27 cases (29.6%; mean of 4.6pg/ml), in NPH patients in 1/9 cases (11.1%; mean of 6.4pg/ml) and in the control subjects in 5/10 cases (50%; mean of 1.6pg/ml) with no significant differences as regards mean concentration and frequency of detectable BDNF in CSF. The decrease of BDNF serum levels in AD and NPH may reflect a lack of trophic support and thus contribute to progressive degeneration in both diseases. In contrast to serum, CSF seems to be no useful source to determine BDNF in AD or NPH because of too low concentrations. Further examinations have to follow to elucidate the potential sources and the meaning of reduced BDNF levels in the blood in AD and NPH.

Increased BDNF serum concentration in fibromyalgia with or without depression or antidepressants.

Fibromyalgia (FM) is still often viewed as a psychosomatic disorder. However, the increased pain sensitivity to stimuli in FM patients is not an "imagined" histrionic phenomena. Pain, which is consistently felt in the musculature, is related to specific abnormalities in the CNS pain matrix. Brain-derived neurotrophic factor (BDNF) is an endogenous protein involved in neuronal survival and synaptic plasticity of the central and peripheral nervous system (CNS and PNS). Several lines of evidence converged to indicate that BDNF also participates in structural and functional plasticity of nociceptive pathways in the CNS and within the dorsal root ganglia and spinal cord. In the latter, release of BDNF appears to modulate or even mediate nociceptive sensory inputs and pain hypersensitivity. We were interested, if BDNF serum concentration may be altered in FM. The present pilot study assessed to our knowledge for the first time BDNF serum concentrations in 41 FM patients in comparison to 45 age-matched healthy controls. Mean serum levels of BDNF in FM patients (19.6 ng/ml; SD 3.1) were significantly increased as compared to healthy controls (16.8 ng/ml; SD 2.7; p<0.0001). In addition, BDNF serum concentrations in FM patients were independent from age, gender, illness duration, preexisting recurrent major depression and antidepressive medication in low doses. In conclusion, the results from our study indicate that BDNF may be involved in the pathophysiology of pain in FM. Nevertheless, how BDNF increases susceptibility to pain is still not known.

Assessment of DNA damage in WBCs of workers occupationally exposed to fumes and aerosols of bitumen.

We conducted a cross-shift study with 66 bitumen-exposed mastic asphalt workers and 49 construction workers without exposure to bitumen. Exposure was assessed using personal monitoring of airborne bitumen exposure, urinary 1-hydroxypyrene (1-OHP), and the sum of 1-, 2 + 9-,3-,4-hydroxyphenanthrene (OHPH). Genotoxic effects in WBC were determined with nonspecific DNA adduct levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and the formation of DNA strand breaks and alkali-labile sites. Concentration of fumes and aerosols of bitumen correlated significantly with the concentrations of 1-OHP and OHPH after shift (r(s) = 0.27; P = 0.03 and r(s) = 0.55; P < 0.0001, respectively). Bitumen-exposed workers had more DNA strand breaks than the reference group (P < 0.0001) at both time points and a significant correlation with 1-OHP and OHPH in the postshift urines (r(s) = 0.32; P = 0.001 and r(s) = 0.27; P = 0.004, respectively). Paradoxically, we measured higher levels of DNA strand breaks, although not significant, in both study groups before shift. 8-OxodGuo adduct levels did not correlate with DNA strand breaks. Further, 8-oxodGuo levels were associated neither with personal exposure to bitumen nor with urinary metabolite concentrations. Significantly more DNA adducts were observed after shift not only in bitumen-exposed workers but also in the reference group. Only low-exposed workers had significantly elevated 8-oxodGuo adduct levels before as well as after shift (P = 0.0002 and P = 0.02, respectively). Our results show that exposure to fumes and aerosols of bitumen may contribute to an increased DNA damage assessed with strand breaks.

Decline of immune responsiveness: a pathogenetic factor in Alzheimer's disease?

The involvement of immunological alterations in the pathogenesis of Alzheimer's disease (AD) is widely discussed. Hitherto, findings on systemic immunological alterations are inconsistent. We measured the concentrations of the pro-inflammatory cytokines IL-1beta, IL-2, IL-6, and TNF-alpha, and of the soluble receptors sIL-2r, sIL-6r, and sTNF-alphar, in cerebrospinal fluid (CSF) and serum of 20 Alzheimer patients and 21 controls. Moreover, we studied levels of the pro-inflammatory IL-6, Il-12, IFN-gamma, and TNF-alpha, and of the anti-inflammatory IL-5 and IL-13 in stimulated blood cell cultures from 27 AD patients and 25 controls. The levels in CSF and serum were diminished in AD or under detection limit. In mitogen-stimulated blood cultures we found a significant decrease of pro- and anti-inflammatory cytokines in the AD group. Our data suggest a general decline of immune responsiveness in AD. Based on the recent research, an impaired immune response may be considered as a pathogenetically relevant factor in AD. With respect to the putative role of ageing in AD, we assume a premature immunosenescence contributing to the Alzheimer's pathology.

Autoantibodies to serotonin in serum of patients with psychiatric disorders.

Antibodies to serotonin in serum were investigated by ELISA in patients with paranoid schizophrenia (N=27), schizoaffective psychosis (N=38), depression (N=67), Alzheimer's disease (N=21), chronic alcoholism (N=43), rheumatoid arthritis (N=25), and multiple sclerosis (N=16), and in healthy volunteers (N=60). Increased antibody reactivity to serotonin was found in schizoaffective psychosis, chronic alcoholism, and rheumatoid arthritis. Decreased antibody reactivity to serotonin was found in multiple sclerosis and depression. These anti-serotonin antibodies belong to the class of so-called natural autoantibodies. Alterations of these natural autoantibodies could indicate a disturbance to the immune system. It is possible that these antibodies could also influence receptor function. Autoantibodies to neurotransmitters in a wide spectrum of psychiatric disorders have not previously been reported.

Altered serum IgG levels to α-synuclein in dementia with Lewy bodies and Alzheimer's disease.

Natural self-reactive antibodies in the peripheral blood may play a considerable role in the control of potentially toxic proteins that may otherwise accumulate in the aging brain. The significance of serum antibodies reactive against α-synuclein is not well known. We explored serum IgG levels to monomeric α-synuclein in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) with a novel and validated highly sensitive ELISA assay. Antibody levels revealed stark differences in patients compared to healthy subjects and were dependent on diagnosis, disease duration and age. Anti-α-synuclein IgG levels were increased in both patient groups, but in early DLB to a much greater extent than in AD. Increased antibody levels were most evident in younger patients, while with advanced age relatively low levels were observed, similar to healthy individuals, exhibiting stable antibody levels independent of age. Our data show the presence of differentially altered IgG levels against α-synuclein in DLB and AD, which may relate to a disturbed α-synuclein homeostasis triggered by the disease process. These observations may foster the development of novel, possibly preclinical biomarkers and immunotherapeutic strategies that target α-synuclein in neurodegenerative disease.

Osteopontin is elevated in Parkinson's disease and its absence leads to reduced neurodegeneration in the MPTP model.

In the pathogenesis of Parkinson's disease (PD), oxidative and nitrosative stress, apoptosis, mitochondrial dysfunction, and excitotoxicity are involved, i.e., processes in which osteopontin (OPN) may also play a role. We have studied in PD patients serum and cerebrospinal fluid (CSF) concentrations of OPN, its immunohistochemical presence in substantia nigra (SN) and tested in OPN-null mice the impact of this protein on MPTP-induced neurodegeneration. PD was accompanied by increased OPN levels in the body fluids. Higher serum levels were associated with more severe motor symptoms. CSF levels were positively associated with concomitant dementia and negatively associated with dopaminergic treatment. In human SN, OPN was expressed in neurons, in their Lewy bodies and in microglia. Loss of tyrosine-hydroxylase-positive cells in the SN and of dopaminergic fibers in the striatum was reduced 3 weeks after MPTP intoxication in OPN-null mice. These data suggest that OPN is involved in PD-associated neurodegeneration.

Irritative effects of fumes and aerosols of bitumen on the airways: results of a cross-shift study.

Possible health hazards of fumes and aerosols of bitumen are in discussion, and data on their adverse effects on human airways under current exposure conditions are limited. To assess the irritative effects of exposure to fumes and aerosols of bitumen on the airways, a cross-sectional cross-shift study was conducted including external and internal exposure measurements, spirometry and especially non-invasive methods like nasal lavage collection and induction of sputum in order to identify and evaluate more precisely inflammatory process in the upper and lower airways. The cross-shift study comprised 74 mastic asphalt workers who were exposed to fumes and aerosols of bitumen and 49 construction workers without this exposure as reference group. Questionnaire, spirometry, ambient monitoring and urinary analysis were performed. Humoral and cellular parameters were measured in nasal lavage fluid (NALF) and induced sputum. For data analysis, a mixed linear model was performed on the different outcomes with exposure group, time of measurement (pre-, post-shift), current smoking, German nationality and age as fixed factors and subjects as random factor. Based on personal exposure measurements during shift, mastic asphalt workers were classified into a low (< or =10 mg/m(3); n = 46) and a high (>10 mg/m(3); n = 28) exposure group. High exposure was accompanied by significant higher urinary post-shift concentrations of 1-hydroxypyrene and the sum of hydroxyphenanthrenes. Acute respiratory symptoms were reported more frequently in the high exposure group after shift. Significant cross-shift declines in lung function parameters (forced expiratory volume in 1 s [FEV(1) (% predicted)] and forced vital capacity [FVC (% predicted)]) were measured in mastic asphalt workers. Pre-shift FEV(1) (% predicted) and FVC (% predicted) were higher in the low exposure group. In pre- and post-shift NALF samples, interleukin (IL)-1beta-, IL-8- and total protein concentrations were lower in the low exposure group compared to the reference and the high exposure group. Pre- and post-shift neutrophil percentages in both nasal and sputum samples were also lower in the low exposure group. Significantly higher pre- and post-shift sputum concentrations of IL-8, IL-6, nitrogen oxide (NO) derivatives and total protein were detected especially in highly exposed workers. Irritative effects of exposure to fumes and aerosols of bitumen on the upper and lower airways were apparent, especially in mastic asphalt workers with exposure above 10 mg/m(3).

[Predictive diagnostics in chorea huntington: psychotherapeutic implications for counselling]. / Prädiktive Diagnostik bei Chorea Huntington: Psychotherapeutische Aspekte der Beratung von Risikopersonen.

The progress in molecular genetic research leads to an increased availability of predictive diagnosis of inherited diseases. However, the prediction of an incurable illness is inevitably related with severe psychic conflicts. Based on the relevant literature, the psychological implications of predictive diagnostics are outlined, and counselling strategies for persons vulnerable for an inherited disease are summarized. In spite of numerous studies with persons at risk the prediction of the individual reaction remains rather difficult. Unconscious expectations play an essential, but underestimated role for the test motivation and coping strategies. Relieving the pressure of time supposed by most of the risk persons seems necessary to allow a deeper understanding of motivation and development of sound coping strategies. After disclosure of the test result, an ongoing counselling should be offered to all family members.

Posttranscriptional regulation of the immediate-early gene EGR1 by light in the mouse retina.

Synaptic plasticity is modulated by differential regulation of transcription factors such as EGR1 which binds to DNA via a zinc finger binding domain. Inactivation of EGR1 has implicated this gene as a key regulator of memory formation and learning. However, it remains puzzling how synaptic input can lead to an up-regulation of the EGR-1 protein within only a few minutes. Here, we show by immunohistochemical staining that the EGR-1 protein is localized in synapses throughout the mouse retina. We demonstrate for the first time that two variants of Egr-1 mRNA are produced in the retina by alternative polyadenylation, with the longer version having an additional 293 base pairs at the end of the 3'UTR. Remarkably, the use of the alternative polyadenylation site is controlled by light. The additional 3'UTR sequence of the longer variant displays an even higher level of phylogenetic conservation than the coding region of this highly conserved gene. Additionally, it harbours a cytoplasmic polyadenylation element which is known to respond to NMDA receptor activation. The longer version of the Egr-1 mRNA could therefore rapidly respond to excitatory stimuli such as light or glutamate release whereas the short variant, which is predominantly expressed and contains the full coding sequence, lacks the regulatory elements for cytoplasmic polyadenylation in its 3'UTR.

T-wave response: a sensitive test for latent alcoholic polyneuropathy.

To date, the H-reflex is the most sensitive test to measure nerve conduction velocity in alcoholic polyneuropathy. Analogous to the H-reflex, we investigated the T-wave response from the soleus muscle using a hand-held reflex hammer. Twenty-four inpatients suffering from chronic alcoholism and 24 healthy volunteers were recruited. All probands had a careful neurological examination and were graded (PNP-classifications). The T- and H-reflexes were measured. In the clinical examination, only a few patients exhibited symptoms of alcoholic PNP. However, when the autonomic nervous system was also tested, 50% exhibited signs of alcoholic PNP. Both the T- and H-reflex responses were pathologically retarded, indicating latent alcoholic PNP in 60% of the patients. Thus the main finding in our study is the difference between clinical and electrophysiological examinations: only a few of the patients had neurological symptoms for alcoholic PNP but 14 patients (60%) exhibited a so-called latent, subclinical alcoholic PNP by showing delayed reflex latencies. Measuring the T-wave proved to be a simple and painless screening method for diagnosis and monitoring of alcoholic PNP. Among the clinical tests the best indicator for alcoholic PNP was the test for autonomous alcoholic PNP.