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The vascular niche of malignant gliomas is a key compartment that shapes the immunosuppressive brain tumor microenvironment (TME). The blood-brain-barrier (BBB) consisting of specialized endothelial cells (ECs) and perivascular cells forms a tight anatomical and functional barrier critically controlling transmigration and effector function of immune cells. During neuroinflammation and tumor progression, the metabolism of the essential amino acid tryptophan (Trp) to metabolites such as kynurenine has long been identified as an important metabolic pathway suppressing immune responses. Previous studies have demonstrated that indoleamine-2,3-dioxygenase-1 (IDO1), a key rate-limiting enzyme in tryptophan catabolism, is expressed within the TME of high-grade gliomas. Here, we investigate the role of endothelial IDO1 (eIDO1) expression for brain tumor immunity. Single-cell RNA sequencing data revealed that in human glioma tissue, IDO1 is predominantly expressed by activated ECs showing a JAK/STAT signaling pathway-related CXCL11+ gene expression signature. In a syngeneic experimental glioma model, eIDO1 is induced by low-dose tumor irradiation. However, cell type-specific ablation of eIDO1 in experimental gliomas did not alter frequency and phenotype of tumor-infiltrating T cells nor tumor growth. Taken together these data argue against a dominant role of eIDO1 for brain tumor immunity.

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Terrestrial snails which live under dry and hot conditions need efficient mechanisms of adaptation to counteract the problems of desiccation and over-heating. A profoundly heat tolerant snail species is the Mediterranean Xeropicta derbentina, exhibiting different shell colour morphs ranging from pale white to darkly banded. Considering that dark-pigmented snails are believed to have a disadvantage due to faster heating, we investigated possible differences in the stress markers Hsp70 and lipid peroxideation between four pre-defined colour morphs which were exposed to different temperatures for eight hours. The highest Hsp70 levels were observed in response to 38-40 °C. Levels decreased when this temperature was exceeded. Snails of a pre-defined colour category 3 (with a large black band at the umbilicus side of the shell) showed the most prominent Hsp70 response. Lipid peroxideation levels also showed a maximum at 38 °C but displayed a second peak at rather high temperatures at which the Hsp70 level already had decreased (45-48 °C). Particularly pure white snails (category 1) and the most pigmented ones (category 4) were found to have different levels of lipid peroxidation at 38 °C and 45 °C compared to the other morphs. A hypothesis involving a combined two-phase defence mechanism, to which both, the Hsp70 protection system and the antioxidant defence system, may contribute, is discussed.

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Idiopathic Parkinson's disease (PD) is a common neurodegenerative disorder with prominent motor symptoms. However, depression is common in PD, affecting about 40% of PD patients. Since there is extensive evidence of degeneration of serotonin (5HT) neurons and loss of the 5HT transporter (5HTT) in PD, we assessed whether a functional polymorphism in the promoter of the 5HTT gene (5HTT gene-linked polymorphic region, 5HTTLPR), which determines high or low 5HT uptake, is associated with depressive symptomatology in PD patients. We found that patients with the short allele of the 5HTTLPR had significantly higher scores on the Hamilton Depression Scale. A functional promoter polymorphism of the monoamine oxidase A (MAOA) gene showed no association. Thus, the 5HTTLPR but not the MAOA gene promoter-associated polymorphism may be a risk factor for depression in PD patients, while neither polymorphism increases the risk for development of Parkinson's disease itself.

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BACKGROUND: Impairments of articulation, respiration, and phonation are a common symptom of Parkinson's disease and may result in reduced communication. Previous observations have shown a high incidence of laryngeal abnormalities. However, no relevant data were available for gender differences of laryngeal abnormalities in Parkinson's disease. METHOD: Thirty-nine female and 61 male patients with Parkinson's disease were examined. The laryngeal function was explored by laryngoendoscopy and laryngostroboscopy in respiration and production of [i:] during normal pitch and normal loudness. RESULTS: Abnormal function of vocal cord abduction and adduction were observed in 54% of the women and 39% of the men; more patients had reduced abduction. Bilateral vocal fold atrophy was seen in 36% of the women and 56% of the men, while 41% of the women and 57% of the men had a bilateral hypertrophy ventricular fold. Phase closure incompetence was found in 60.5% of the women and 49% of the men. Abnormal amplitude and mucosal waveform were seen in more male patients, while 30.7% of the women and 25% of the men had a laryngeal tremor. Gender differences were observed with respect to common laryngeal symptoms. CONCLUSION: This study concludes that laryngeal abnormalities in Parkinson's disease show a high degree of gender differences. The percentage of patients with abnormal abduction of the vocal cord was higher than has been reported in other studies. Vocal-fold bowing appear to be related to vocal fold atrophy. Although patients with Parkinson's disease frequently exhibit vocal fold atrophy, other mechanisms and causes should be discussed. Patients with tremor and common laryngeal symptoms were observed. These findings were not expected and further studies of this phenomena would be useful.

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BACKGROUND: Immune mechanisms seem to contribute to the degenerative process in Alzheimer's disease. Antibodies directed against animal brain tissue were found in sera of Alzheimer's patients. METHODS: Antibodies were measured in sera of 25 Alzheimer's patients and a comparison group of 25 age- and sex-matched controls. Sera were tested for their immunological response to various brain structures of postmortem human brain tissue. RESULTS: In 8 patients with Alzheimer's disease perinuclear antibodies directed against microglia were found in amygdala and frontal cortex. In the control group 1 subject showed antibody binding to microglia. CONCLUSIONS: Perinuclear antibodies to microglia may play a role in tissue destruction of Alzheimer's disease. These data add to the evidence that immune mechanisms play a role in the pathophysiology of Alzheimer's disease.

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In advanced stages of Parkinson's disease problems of speech, mobility and balance occur with a high frequency. Although the symptoms of the disease can be treated by specific and individual pharmacotherapy, some of the severe symptoms such as freezing, falls, unsteadiness, and dysarthria persist. To evaluate the potential use of additional therapies, a diagnosis of all current symptoms must be performed; afterwards a specific individual treatment can be decided by the therapist based on objective data. Only if the initial evaluations of a new therapy show improvement, will such therapies be subjected to long-term evaluation, which should be also performed by the patient. This contribution presents examples of a useful prediagnosis and of the evaluation of the conventional physiotherapy. Also, two new methods are evaluated as additional therapies: low-frequency muscle stimulation and magnetic pulse therapy. A thorough symptomatic diagnostic view, specifically directed additional therapy and the careful evaluation of the use of therapies provide the only meaningful treatment of Parkinson's disease.

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A number of neurodegenerative diseases including Parkinson's disease (PD) have been shown to be associated with polymorphic variants of mitochondrial DNA. The A4336G mutation in the tRNA(Gln) gene was reported to occur at a higher frequency in individuals with Parkinson's disease and Alzheimer's disease (AD) than in age-matched controls. Similarly, we recently noted an elevated frequency of alterations at positions 15927 and 15928 in the tRNA(Thr) gene, resulting in the loss of a HpaII site, in patients suffering from multiple sclerosis (MS) with severe optic involvement. Here we report on the result of screening 100 PD patients and 100 age- and sex-matched controls for the presence of the A4336G mutation and the loss of the HpaII site in the tRNA(Thr) gene. Our result shows that loss of the HpaII site is significantly more frequent in patients than in controls. In contrast, we were not able to detect a difference in the frequency of the A4336G mutation in the tRNA(Gln) gene between patients and controls.

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UNLABELLED: Preferential maternal transmission in familial cases and the occasional association of multiple sclerosis (MS) and LHON suggests an involvement of mtDNA mutations in the aetiology of MS. MATERIAL & METHODS: DNA obtained from 100 MS patients with pathological alterations in visually evoked potentials and 100 controls, was used for PCR amplification of mtDNA segments. Mutations were identified by restriction enzyme analysis and DNA sequencing. RESULTS: Whereas primary LHON mutations are not detected, MS patients show a higher percentage of secondary LHON mutations, usually in a combinatorial manner, than controls. Two neighbouring base pair substitutions that are alleles in a HpaII-polymorphism in the mt tRNA(Thr) gene are significantly more frequent in MS patients than in controls (p = 0.00018). CONCLUSION: Primary LHON mutations are not characteristic for MS with optic involvement, but secondary LHON mutations and two substitutions abolishing a HpaII site in the mt tRNA(Thr) gene may contribute to the aetiology of MS with optic involvement.

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The pathogenesis of schizophrenia is still unknown. In a previous study we found antibrain antibodies in the sera of schizophrenic patients, but not in normal controls. Therefore we have further examined the sera of schizophrenic patients versus normal controls, increasing the number of brain areas, to explore whether certain areas were involved more often than others in the antibody binding process. The sera of 50 patients suffering from an acute episode of schizophrenia (classified by DSM III-criteria) were tested. 70% of the patients showed antibody binding, while only 12% of the age- and sex-matched controls were positive. The binding was mediated by IgG- as well as IgM-antibodies. Amygdala, frontal cortex, cingulate gyrus, and septal area were the prominent targets, while hippocampus, parahippocampal gyrus, entorhinal cortex, putamen, mamillary bodies and head of the caudate nucleus were involved to a lesser degree. Binding was not present to nucleus olivaris, to the thyroid gland or to HEp-2 cells, which we included to test for unspecific antinuclear factors. Longterm studies of schizophrenic patients and biochemical analyses of the antigen(s) involved are in progress.

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Using an enzyme-linked immunoadsorbent assay, we looked, whether the formation of idiotype-anti-idiotype complexes was responsible for the absence of antibodies in the sera of MS patients. We tested 18 relapsing-remitting and 26 chronic progressive patients versus 44 age- and sex-matched controls. We did not find elevated titres of immune complexes in the sera of the multiple sclerosis patients.

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Sera of 30 chronic alcoholic patients and 30 age-matched and gender-matched controls were examined for antibodies to brain tissues. We performed an indirect immunofluorescence assay using the patients' and controls' sera as first antibodies, and fluorescein-conjugated anti-human-immunoglobulin Ig-A,Ig-G and Ig-M as second antibodies, on frozen sections of normal human brain. Binding to neuronal cell nuclei of frontal cortex and septal area was found in 40% of patients, but only in 6.7% of controls. The antibodies belonged to the IgM, and additionally sometimes the IgA and IgG subclass. The relevance of these antibodies for the development of brain disease in chronic alcoholic patients is discussed.

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The sera of 30 patients suffering from schizophrenia (DSM III) and 30 neurological controls were tested for antibrain antibodies in a blind indirect immunofluorescence assay. We found IgG- and IgM-binding in the sera of 22 patients, but only 4 out of the 30 age- and sex-matched controls. The binding was mainly directed to neurons from the frontal cortex and septal areas, areas, which are regarded as important in the development of schizophrenic illness. These preliminary data are presented, to encourage other immunological studies in schizophrenia research.

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Using a blind indirect immunofluorescence assay we examined the sera of 30 multiple sclerosis (MS) patients and 30 age- and sex-matched controls for autoantibodies to brain tissue. Binding was found in 33% of the patients' sera and in only 3% of the controls' sera. Positive and negative patients differed significantly in the course of MS, since eight of the ten positive patients showed a chronic progressive form. None of the patients with a large deficit in a chronic state showed antibodies to brain tissue, while eight of the 11 active chronic progressive cases were positive. Therefore it seems possible that these brain antibodies could be used as an activity parameter, at least for this form of the disease.

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T-lymphocyte subpopulations were examined in the peripheral blood of 30 acute schizophrenic patients and compared with 30 age- and sex-matched patients with non-inflammatory neurological diseases. Significant increases in the numbers of Pan-T and T-helper cells were found in schizophrenic patients compared to the controls. The interindividual variability of values in the group of schizophrenic patients was greater than in the group of neurological patients.

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Immunoglobulins were separated from sera of 40 multiple sclerosis (MS) patients and 40 healthy controls by density and affinity chromatography. In IgM and IgG fractions of the sera of patients and controls no lymphocyte-specific binding could be detected with the help of FITC-conjugated anti-mu and anti-Fc antibodies.

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T-cell subpopulations were tested in multiple sclerosis (MS) patients before and after cyclophosphamide (n = 38) and corticotropin (n = 37) treatment and physiotherapy (n = 30). There were no specific changes of subset ratios immediately after immunosuppressive treatment. However, T-cell subpopulations showed great day-to-day variations in MS patients.

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