Potential role for the narcolepsy- and multiple sclerosis-associated HLA allele DQB1*0602 in schizophrenia subtypes.
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Adult↗
Biomedical subjects
N Müller
Publications and source records attributed to N Müller.
Lyme disease presenting as Tourette's syndrome.
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Ceftriaxone↗
Distinct prevalence of antibodies to the E2 protein of GB virus C/hepatitis G virus in different parts of the world.
Since the identification of the new human virus, GB virus C (GBV-C)/hepatitis G-virus (HGV), in 1995/1996, reverse transcription polymerase chain reaction remained the sole available diagnostic tool for GBV-C/HGV infection. Recently, a serologic test based on the detection of antibodies to the putative envelope protein 2 (anti-E2) has been introduced. We used this assay for a seroepidemiological survey including 3,314 healthy individuals from different parts of the world, 123 patients from Germany who were suspected to have an increased risk of acquiring GBV-C/HGV infection, 128 multiple organ donors, and 90 GBV-C/HGV RNA positive persons. In European countries, anti-E2 seropositivity ranged from 10.9% (Germany) to 15.3% (Austria). In South Africa (20.3%) and Brazil (19.5%), even higher anti-E2 prevalence rates were recorded. In Asian countries like Bhutan (3.9%), Malaysia (6.3%), and the Philippines (2.7%), anti-E2 positivity was significantly lower. GBV-C/HGV anti-E2 prevalence in potential "risk groups," i.e., patients on hemodialysis and renal transplant recipients, did not vary significantly from anti-E2 seroprevalence in German blood donors. Anti-E2 and GBV-C/HGV RNA were found to be mutually exclusive, confirming the notion that anti-E2 has to be considered as a marker of past infection.
Antibodies, Viral↗
Technical aspects and performance in collecting peripheral blood progenitor cells.
The combination of effective mobilization protocols and efficient use of apheresis systems has led to a rapid growth of peripheral blood progenitor cell (PBPC) transplantation. The specifications for these procedures are changing towards more automated systems for standard collections to minimize operator interaction and to collect PBPC efficiently from donors and patients and also to reduce the collection of undesired cells such as polymorphonuclear cells and platelets using functionally closed, sterile environments for collection, in keeping with good manufacturing practice guidelines. The increasing need for pediatric procedures requires apheresis systems that run efficiently at low flow rates. It is also desirable to have a low extracorporeal volume. Technical considerations related to PBPC harvesting should include strategies facilitating more efficient collection such as large-volume leukapheresis, which is able to increase the PBPC yield. The most common complication related to apheresis is catheter occlusion, and care should be taken to prevent thrombosis and maintain vascular access. However, refinement and improvement of collection techniques continue to add to the armamentarium of current approaches for cancer and nonmalignant conditions and will enable the development of new strategies.
Blood Component Removal↗
Autoantibodies against 60-kDa heat shock protein in schizophrenia.
Immunological abnormalities in schizophrenic patients have been reported for many years. However, the question of whether these parameters are involved in the pathophysiology of the disorder or represent treatment effects is still not answered. We investigated a combination of humoral and soluble immune parameters in 30 unmedicated schizophrenic patients before and during antipsychotic treatment and in 31 healthy controls. The aim of our study was to unravel an underlying immune process, to elucidate the influence of neuroleptic treatment and to identify a subgroup of schizophrenics. Antibodies against human 60-kDa heat-shock protein (HSP60), serum levels of soluble ICAM-1 and IL-2R were determined and correlated with parameters of blood-brain barrier and of psychopathology. In 10% of the drug-free but in 20% of the medicated schizophrenics, especially in females, we observed immunoreactivity against HSP60, high levels of IgG in CSF and a blood-brain barrier impairment. The high HSP antibody titres correlated with high levels of sIL-2R and sICAM-1. Only one of the controls showed antibodies against HSP60. Our results suggest that the observed immunological alterations are more pronounced during neuroleptic treatment than in the drug-free state. Whether or not this differential response to treatment with altered antibody production represents a subgroup of patients has yet to be determined.
Adolescent↗
Molecular and immunodiagnostic investigations on bovine neosporosis in Switzerland.
Neospora caninum has gained considerable attention through its role in the aetiology of bovine abortion. Due to its close phylogenetic relationship with Toxoplasma gondii, respective unequivocal differential diagnosis deserves special consideration. In order to evaluate the diagnostic performance of molecular and immunodiagnostic techniques and to provide insights into the epidemiological significance of bovine neosporosis in Switzerland, we conducted a study on 83 cases of bovine abortion: of these, 24 (29%) foetal brains were positive by Neospora-PCR, six of these foetuses were simultaneously seropositive in Neospora-IFAT and/or somatic antigen-ELISA. Conversely, four (5%) foetal brains were considered positive by Toxoplasma-PCR, two of which were also seropositive in the Toxoplasma-P30-ELISA and/or direct agglutination test. The seroprevalence in 1689 cattle sera obtained from 113 diary farms was 11.5% (95% confidence interval: 9.2-13.8) by Neospora-somatic antigen-ELISA were and 10.7% (95% confidence interval: 8.3-12.6) by Toxoplasma-P30-ELISA. From the same samples, 1.1%, less than statistically expected, were positive in both ELISA. Within selected groups of cow-calf farms, the seroprevalence determined using the Neospora-somatic antigen-ELISA was 14% (95% confidence interval 5.0-23.0) for dams and 15% (95% confidence interval: 3.0-28.0) for offspring calves. Seroprevalences determined by Toxoplasma-P30-ELISA were 8% (95% confidence interval: 4.0-12.0) for dams and 3% (95% confidence interval: 0.3-6.0) for calves. None of the sera gave a positive reaction in both ELISA. Our data indicated that prenatal neosporosis appears as an important cause of bovine abortion in Switzerland.
Abortion, Veterinary↗
Antigenic variation and the murine immune response to Giardia lamblia.
The protozoan parasite Giardia lamblia is an important causative agent of acute or chronic diarrhoea in humans and various animals. During infection, the parasite survives the host's reactions by undergoing continuous antigenic variation of its major surface antigen, named VSP (variant surface protein). The VSPs form a unique family of cysteine-rich proteins that are extremely heterogeneous in size. The relevance of antigenic variation for the survival in the host has been most successfully studied by performing experimental infections in a combined mother/offspring mouse system and by using the G. lamblia clone GS/M-83-H7 (human isolate) as model parasite. In-vivo antigenic variation of G. lamblia clone GS/M-83-H7 is characterised by a diversification of the intestinal parasite population into a complex mixture of different variant antigen types. It could be shown that maternally transferred lactogenic anti-VSP IgA antibodies exhibit cytotoxic activity on the Giardia variant-specific trophozoites in suckling mice, and thus express a modulatory function on the proliferative parasite population characteristics. Complementarily, in-vitro as well as in-vivo experiments in adult animals indicated that non-immunological factors such as intestinal proteases may interfere into the process of antigen variation in that they favour proliferation of those variant antigen-type populations which resist the hostile physiological conditions within the intestine. These observations suggest that an interplay between immunological and physiological factors, rather than one of these two factor alone, modulates antigenic diversification of a G. lamblia population within an experimental murine host and thus influences the survival rate and strategy of the parasite.
Animals↗
Psychoneuroimmunology and the cytokine action in the CNS: implications for psychiatric disorders.
1. Parallel to the current rapid development of new immunological methods, immune mechanisms are gaining more importance for our understanding of psychiatric disorders. The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system. 2. The topical literature dealing with the interactions of immune system, neurotransmitters, psychological processes, and psychiatric disorders, especially in relation to cytokines, is reviewed. 3. An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described. Cytokines, actively transported into the CNS, play a key role in this immune activation. It was recently observed that cytokines activate astrocytes and microglia cells, which in turn produce cytokines by a feedback mechanism. Moreover, they strongly influence the dopaminergic, noradrenergic, and serotonergic neurotransmission. 4. There are indications that the cascade of cytokines can be activated by neuronal processes. These findings close a theoretical gap between stress and its influence on immunity. Psychomotor, sickness behavior and sleep are related to IL-1; disturbances of memory and cognitive impairment are to IL-2, in part also to TNF-alpha. The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia, and IL-6, on depressive disorders. 5. Although single cytokines most likely do not have a specificity for certain psychiatric disorders, a characteristic pattern of cytokine actions in the CNS, including influences of the cytokines on the blood-brain barrier, seems to play a role in psychiatric disorders. This may have therapeutic implications for the future.
Animals↗
Platelet collection with the Amicus and the AS.TEC 204 blood cell separators.
BACKGROUND: Platelet collection with two new blood cell separators was compared with respect to platelet yield, separation efficiency, white cell (WBC) contamination, and measures of component quality. Both machines offer a menu for the collection of a desired platelet yield. The harvesting of a definite platelet yield is a means of collecting a standardized therapeutic platelet dose. STUDY DESIGN AND METHODS: One hundred seventy-two platelet collections were carried out with different protocols in the two devices (Amicus and AS.TEC 204). For that reason, healthy donors underwent plateletpheresis procedures using the continuous- and discontinuous-flow systems. Separations with a definite endpoint volume and the option of collecting a desired platelet yield of 5.5 x 10(11) in the Amicus and 3.3 x 10(11) in the AS.TEC 204 machine were investigated. RESULTS: With the Amicus blood cell separator, platelet yield (5.02+/-0.46 x 10[11]) and separation efficiency (66.9+/-6.2%) were significantly higher than those with the AS.TEC 204 (3.02+/-0.62 x 10[11] and 46.4+/-6.7%, respectively). There was less deviation between the platelet yield and the desired platelet yield in the AS.TEC 204 machine than in the Amicus device. WBC contamination was 2.06+/-2.91 x 10(6) in components obtained from the AS.TEC 204 machine, and 87.5 percent of the platelet concentrates had a WBC content <5 x 10(6). None of the components from the Amicus device contained more than 5 x 10(6) WBCs. Except for platelet morphology score, measures of component quality were almost equal in the platelet concentrates obtained from the studied machines. CONCLUSION: Platelet yield and separation efficiency were significantly higher in the Amicus blood cell separator. The collection of a desired platelet yield was better achieved with the AS.TEC 204 device.
Blood Component Removal↗
Influence of antibodies in mother's milk on antigenic variation of Giardia lamblia in the murine mother-offspring model of infection.
In the present study, neonatal ZU.ICR mice and their mothers were infected with trophozoites of Giardia lamblia clone GS/M-83-H7 expressing the variant surface protein (VSP) H7. The infection experiments included a detailed analysis of the specificities of anti-Giardia immunoglobulin A (IgA) antibodies in mother's milk and a determination of the effects of the milk antibodies on both the growth of the parasite during in vitro cultivation and colonization of the parasite within the intestine of suckling offspring. These investigations revealed that transiently emerging milk IgA antibodies against a variant-specific 314-amino-acid N-terminal region of VSP H7 exhibit a strong parasiticidal effect on VSP H7-type trophozoites both in vitro and in vivo. These findings indicated that parasiticidal effects of local IgA antibodies against the N-terminal part of VSP H7 select for new variant types within the intestinal parasite population of suckling mice. The selective influence of such antibodies promotes in vivo antigenic variation of G. lamblia clone GS/M-83-H7 and modulates the early course of parasite infection in these animals.
Animals↗
Detection of Tritrichomonas foetus by PCR and DNA enzyme immunoassay based on rRNA gene unit sequences.
Tritrichomonas foetus is the causative agent of bovine tritrichomonosis, a sexually transmitted disease leading to infertility and abortion. Diagnosis is hampered by putative contamination of samples with intestinal or coprophilic trichomonadid protozoa which might be mistaken for T. foetus. Therefore, we developed a PCR test optimized for applicability in routine diagnosis. Amplification is based upon primers TFR3 and TFR4 directed to the rRNA gene units of T. foetus. In order to avoid potential carryover contamination by products of previous amplification reactions, conditions were adapted to the use of the uracil DNA glycosylase system. Furthermore, documentation and interpretation of results were facilitated by including a DNA enzyme immunoassay for the detection of amplification products. Specificity was confirmed with genomic material from different related trichomonadid protozoa. The high sensitivity of the test allowed the detection of a single T. foetus organism in diagnostic culture medium or about 50 parasites per ml of preputial washing fluid. The present methods are thus proposed as (i) confirmatory tests for microscopic diagnosis following diagnostic in vitro cultivation and (ii) a direct T. foetus screening test with diagnostic samples.
Animals↗
[Psychiatric disorders: incidence, psychosocial effects and correlation with physical illnesses].
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Adolescent↗
[Extensive stomach ulcers due to Dieffenbachia intoxication in a cat].
Extensive gastric ulceration was diagnosed endoscopically and histologically in a two-year-old cat with haematemesis, anorexia and severe dehydration. Based on history (previous ingestion of leaf pieces of Dieffenbachia) and exclusion of another cause, intoxication with Dieffenbachia was diagnosed. The toxical effect of Dieffenbachia on mucous membranes is probably explained by ejection of calcium oxalate crystals leading to injury of mast cells and a massive histamine release. Supportive treatment including electrolyte infusions, ranitidine, sucralfate, and forced feeding using an endoscopically placed gastrostomy tube resulted in quick clinical recovery of this cat.
Animals↗
Posttranslational modifications of alpha- and beta-tubulin in Giardia lamblia, an ancient eukaryote.
Tubulin of Giardia lamblia, a representative of the oldest eukaryotes, was screened for posttranslational modifications. Mass spectrometry of the carboxy-terminal peptides documents a large number of variants. Both alpha- and beta-tubulin show polyglycylation with up to 20 and 15 extra glycyl residues respectively. Minor variants show a low level of glutamylation without or with glycylation. The glutamylation-specific antibody GT335 detects alpha- and beta-tubulin in immunoblots. The terminal tyrosine is fully retained in alpha-tubulin, which is completely acetylated at Lys-40. Thus except for the detyrosination/tyrosination cycle all posttranslational modifications known for higher eukaryotes are already present in Giardia.
Acetylation↗
Towards a molecular level understanding of protein stabilization: the interaction between lysozyme and sorbitol.
The paper is investigating the mechanism of stabilization of proteins by polyols at the molecular level. It is addressing the interactions of sorbitol, a polyol commonly used as a protein stabilizing agent, with hen egg white lysozyme, a well studied protein. Differential scanning calorimetry shows an increase in denaturation temperature of lysozyme upon addition of sorbitol at a concentration of 250 mM and above. Increasing sorbitol concentration also caused an increase in signal intensity of the CD spectrum of lysozyme in the wavelength region of 280-300 nm. Two-dimensional nuclear magnetic resonance spectroscopy was used to examine interactions between lysozyme and sorbitol. Most significant changes are manifest in the anomalous relaxation properties of Ala and Thr methyl groups indicating modifications of local motions and possibly compression of the entire structure. This is further corroborated by new intra-protein nuclear Overhauser effects in the presence of sorbitol. There is also evidence that water is displaced from the enzyme surface close to Ile-88 upon addition of sorbitol. In combination these results reveal a complex interplay of different interactions. Comparison to NMR-spectra of lysozyme with a bound inhibitor (tri-N-acetyl-glucosamine) shows that the interaction with sorbitol affects spatially disparate regions of the protein.
Calorimetry, Differential Scanning↗
Interleukin-6 is not altered in cerebrospinal fluid of first-degree relatives and patients with Alzheimer's disease.
We investigated interleukin-6 (IL-6) levels in cerebrospinal fluid (CSF) of 25 patients with clinically diagnosed sporadic Alzheimer's disease (AD) and 19 healthy control subjects (HC). For comparison 19 clinically healthy subjects with at least one first-degree relative with clinical or autopsy confirmed AD (CF/AD) were examined. CSF levels of IL-6 did not show statistically significant differences between AD patients, CF/AD and HC subjects. There was no correlation between age, gender, age of onset, degree of cognitive impairment, blood-brain barrier dysfunction and IL-6 values. We could not demonstrate altered CSF concentrations of IL-6 that may indicate an inflammatory response or capability to support neuronal survival in the central nervous system (CNS) of first-degree relatives and patients with AD. We suggest that combined measurement of all parameters of the IL-6-receptor complex could yield more insight in a probably altered IL-6 function.
Adult↗
Characteristics of obsessive-compulsive symptoms in Tourette's syndrome, obsessive-compulsive disorder, and Parkinson's disease.
A high incidence of obsessions and compulsions is documented in basal ganglia disorders, especially in patients with Tourette's syndrome (TS). A comparison of patients with obsessive-compulsive disorder (OCD), TS, and Parkinson's disease (PD) revealed significantly higher total scores in both OCD and TS patients than in a healthy control group on the Maudsley obsessive-compulsive inventory (MOCI) and the Hamburg obsessive-compulsive inventory (HZI-K), two self-report measures of obsessive-compulsive symptoms. On most subscales (especially Checking, Ordering, and Counting/touching), TS patients scored higher than controls. Patients with Parkinson's disease merely scored higher on the subscale 'Ordering' of the HZI-K. Differences between OCD patients and TS patients were evident on the MOCI subscales 'Checking' and 'Slowness/Repetition' as well as on the MOCI total score and on the HZI subscales 'Cleaning' and 'Obsessive Thoughts'. On these scales, TS patients reported fewer symptoms than OCD patients. Stepwise discriminant analysis with preselected single items as variables was used to look for specific symptom patterns of OCD and TS. Seventy-eight percent of the patients could be correctly classified with respect to their diagnoses on the basis of only two items of the HZI-K. One item asks for fearful obsessive thoughts, which was found in 90% of the OCD patients; the second item represented echo phenomena, found in 56% of the TS patients. It is concluded that considering specific patterns of obsessive-compulsive psychopathology may contribute to a more reliable differential diagnosis in OCD and TS and help to avoid misdiagnosis of OCD in TS patients.
Adult↗
Collection of platelets and peripheral progenitor cells with the fresenius AS.TEC 204 blood cell separator.
The aim of the present study was to clinically evaluate the blood cell separator AS.TEC 204. One hundred fifteen platelet collections were carried out with the dual or single needle procedure. Platelet yield was 3.21 +/- 0.80 x 10(11) (mean +/- standard deviation) and 59.1% of the collections showed platelet counts > or = 3.0 x 10(11). Leukocyte contamination was 1.77 +/- 2.81 x 10(6) and 89.0% of the platelet concentrates had a white blood cell content < 5 x 10(6). Using a dual needle technique with an alternating interface adjustment, all of the products were contaminated with less than 1 x 10(6) leukocytes. Furthermore, 23 peripheral progenitor cell collections were performed in 12 patients and three allogeneic donors. Median numbers of harvested CD 34 antigen expressing cells/kg body weight were 0.78 (range 0-4.7) and 3.67 x 10(6) (range 2.2-5.23), respectively. We conclude that platelet and progenitor cell collections can be carried out with efficient results. The collections were well tolerated by the donors.
Adult↗