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Biomedical subjects

N Müller

Publications and source records attributed to N Müller.

At least 145 records · Page 8Linked to original sources
PubMed1997

Saccades in Gilles de la Tourette's syndrome.

Gilles de la Tourette's syndrome (GTS) is presumed to be an inherited disorder with an unclear pathophysiology. An involvement of the basal ganglia is suspected. Besides vocal tics, one of the main symptoms is the presence of motor tics. As eye movements are a specialized part of the motor system, we investigated whether they differed in some typical way in GTS patients. To study the control of saccades in GTS, different paradigms were used to elicit saccades, which were either externally triggered and visually guided or internally triggered and without visual target. GTS patients (n = 10) showed a significant increase of the latency of antisaccades, a highly impaired performance of sequences of memory-guided saccades, and an isolated reduction of the peak velocity in the antisaccades. Overall the results were similar to those found with similar paradigms in patients with Huntington's disease (HD). In analogy to the known pathology of HD, these findings can be attributed to ascending loops from the basal ganglia that inappropriately activate the frontal cortex, especially some of the eye movement-related areas there. This impairment seems to be a rather specific effect, since some oculomotor features that are preserved by structures of the frontal cortex, such as the effect of a fixation target on saccadic latency ("gap effect"), were normal.

Adolescent↗
PubMed1997

Neuroleptic treatment increases soluble IL-2 receptors and decreases soluble IL-6 receptors in schizophrenia.

The cytokines interleukin-2 (IL-2) and interleukin-6 (IL-6) increase during immune activation, they are released from activated astrocytes and microglial cells in the central nervous system (CNS), and they are able to enhance the catecholaminergic neurotransmission. This study focused on the soluble receptors of IL-2 and IL-6 (sIL-2R, sIL-6R) as a part of the regulation system of IL-2 and IL-6. We studied serum levels of sIL-2R in 30 schizophrenic patients not under neuroleptic medication during an acute exacerbation of the disease and reexamined these patients under neuroleptic treatment after clinical improvement. The sIL-6R levels of 39 schizophrenic patients were estimated under the same conditions. The results were compared with the levels of sIL-2R and sIL-6R in 42 healthy controls. No difference was found between the schizophrenic patients before neuroleptic treatment and the healthy controls. During neuroleptic treatment, however, there was a significant increase of sIL-2R levels and a significant decrease of the sIL-6R levels between the pre- and post-conditions. In comparison with healthy controls, the treatment group also showed increased sIL-2R levels and decreased sIL-6R levels. These results suggest that treatment with neuroleptics is associated with increased sIL-2R and decreased sIL-6R. Since sIL-2R bind and inactivate IL-2, whereas sIL-6R form an active complex with IL-6, the increase of sIL-2R and the decrease of sIL-6R together may reflect a functional down regulation of these activating cytokines. This suggests that neuroleptic therapy has a differentiated immunomodulatory effect.

Adolescent↗
PubMed1997

Functional EEG mapping and SPECT in detoxified male alcoholics.

Fifteen alcoholics diagnosed according to DSM-III-R, who were detoxified for at least 2 weeks and showed no clinical withdrawal signs, were investigated with 16 channel EEG mapping during resting, manumotor and music perception conditions, and were compared with 13 control persons. Single photon emission computed tomography (SPECT) using hexa-methyl-propilene-amine-oxime (HMPAO) labeled with 99m-technetium (99mTc) as tracer was performed separately (in patients only) and submitted to semiquantitative region of interest (ROI) analysis in 2 slices, 6 and 10 cm above canthomeatal line, respectively. Resting EEG showed increased power values in fast beta frequency band for the detoxified alcoholics. On cortical stimulation, patients showed signs of pathological EEG reactivity. Correlations of EEG parameters to cerebral blood flow (CBF) values (patients only) yielded coefficients around zero for all frequency bands (signs of uncoupling). All findings point to organic brain dysfunctions in these patients which extend beyond the period of withdrawal.

Adult↗
PubMed1997

[Role of the cytokine network in the CNS and psychiatric disorders].

There is a strong interrelationship between the immune system, the central nervous system and psychological processes that are suggested to play a pivotal role in the pathogenesis of psychiatric disorders. In schizophrenia and depression, activation of the immune system has been observed repeatedly. Cytokines play a key role in immune activation. They are actively transported into the CNS, but also released from activated glia cells. Cytokines activate glia cells in the CNS to produce other cytokines, and a cascade of cytokine effects may be initiated by this mechanisms. During the past few years, the influence of the cytokines on dopaminergic, noradrenergic and serotonergic neurotransmission and also on the hormones of the hypothalamus-pituitary-adrenal axis has been elucidated. It suggests a pivotal role in psychological processes and psychiatric disorders. For example, in schizophrenia the IL-2 cerebrospinal fluid concentration shows a stronger relationship to the relapse probability than catecholamine metabolites. Although the hypersecretion of IL-2 in schizophrenia and of IL-6 in depression are suggested to play key roles for these disorders, a specificity of certain cytokines for certain psychiatric disorders seems unlikely. Psychomotor, sleep and sickness behavior are influenced by IL-1, disturbances of memory and attention by IL-2, but also by TNF-alpha. From the distribution of cytokine receptors in the CNS conclusions can be drawn regarding the influence of cytokines on psychological processes. The finding that norepinephrine stimulates activated astrocytes to produce IL-6 implies that the cytokine cascade may be activated by neuronal processes under certain conditions. This can lead to a molecular biological explanation of the influences of stress on the immune system. Lastly, influences of the cytokines on blood-brain barrier disturbances and further consequences resulting from the role of the cytokine network in the CNS are discussed.

Blood-Brain Barrier↗
PubMed1997

[Historical and current principles of the design of psychiatric clinics].

At the beginning of the 19th century, institutional care for the insane was established by the various German states. At first, the separation of curable and incurable patients influenced psychiatric care and the construction of hospitals. The combination of care and cure in one hospital in Illenau was a turning point in institutional care. Contradictory tendencies characterized the second half of the 19th century: the integration with general medicine in the cities, on the one hand, the social separation and cure in the seclusion of the countryside, on the other. The characteristic psychiatric construction in different countries was influenced by individual architects. The following building styles were dominant: in England, panoptic architecture; in the United States, linear staggered structures; in France, the "carrés isolś"; and in Germany, the structure of blocks with cross-axes. At the end of the 19th century, the system of pavilions was internationally accepted; occupational therapy and mental care in the countryside were introduced. From the First World War until the end of the 1960s, a standstill in psychiatric buildings was noted in Germany, and institutional care came under increasing criticism. There was a reorientation from the middle of the 1970s as a result of more effective therapeutic possibilities. A variety of complementary institutions, outpatient and partly inpatient therapies, which were recommended by the "Psychiatrie-Enquete", started to be realized. Smaller units and different models of integration of psychiatric care, such as building the hospital next to a general hospital or psychiatric wards within a general hospital, became relevant criteria for planning the construction of psychiatric hospitals, as did the integration into the community and the city. Principles of organization like the construction of a communicative quiet inner room, or grading the rooms from public to private, were structurally integrated. Specific structural requirements for the construction and design of psychiatric hospitals should be evaluated in more detail by post-occupancy methods.

Cross-Cultural Comparison↗
PubMed1997

[Immunoglobulin therapy in Gilles de la Tourette syndrome].

It has known for a long time that Sydenham's chorea and tics, as seen in Gilles de la Tourette's syndrome (GTS), are phenomenologically very similar. Tics may occur as symptoms of acute Sydenham's chorea or persist over years as residual symptoms. Investigating of children suffering from GTS, including obsessive-compulsive symptoms, have provided signs of a poststreptococcal autoimmune process but also shown that treatment based on immunological interventions has been effective. We treated a 14-year-old boy showing all diagnostic criteria of GTS, familial susceptibility, and an increase in the antibody titer of streptococcal antigens with 75 immunoglobulins i.v. over 5 days. Response to this therapy was good regarding motor tics, vocal tics, and behavioral symptoms such as disturbed impulse control which still persisted after 9 months. These findings and the successful therapy underline reports of the literature and point to a pathogenetic mechanism of an immunologically triggered disturbance of the striatal dopaminergic system, at least in a subgroup of GTS.

Adolescent↗
PubMed1997

Periodic limb movements during sleep are a frequent finding in patients with Gilles de la Tourette's syndrome.

Gilles de la Tourette's syndrome (GTS) and restless legs syndrome (RLS) are two different neurological disorders with common features such as involuntary movements. In both disorders a disturbance of the dopaminergic system has been considered among other possible mechanisms. Since periodic leg movements (PLMS) during sleep are the predominant objective finding in RLS, the aim of this study was to investigate sleep parameters in GTS patients with particular emphasis on PLMS. Seven drug-free patients with GTS and seven age- and sex-matched healthy controls were studied polysomnographically, including superficial electromyogram (EMG) leads on all four extremities. A high number of PLMS were found in five of seven, and periodic arm movements in four of seven GTS patients. Total sleep time was significantly lower (P < 0.05) in the GTS patients than in the controls, which confirms earlier findings. The presence of PLMS in GTS might point towards evidence for a pathophysiological relationship between GTS and RLS, which, however, is not supported by the different responses to pharmacological treatments.

Adolescent↗
PubMed1997

Systemic and local antibody response in mice induced by a recombinant peptide fragment from Giardia lamblia variant surface protein (VSP) H7 produced by a Salmonella typhimurium vaccine strain.

Previous experimental infections of mice with the intestinal protozoan Giardia lamblia had revealed that antigenic variation of the parasite was associated with the major surface antigen, named variant surface protein (VSP). In the present study, a gene segment of the VSP (VSPH7) from the well-characterized G. lamblia clone GS/M-83-H7 was expressed in the live-attenuated Salmonella typhimurium vaccine strain LT2M1C. The recombinant vaccine was assessed for its potential to induce both a systemic and a local antibody response in mice. Peroral administration of the vaccine stimulated synthesis of serum IgG and intestinal IgA antibodies directed against Salmonella antigens as well as against VSPH7. With respect to the anti-VSPH7 antibody concentrations, vaccination of animals resulted in systemic and local antibody responses similar to those induced by experimental or natural infections of mice with G. lamblia clone GS/M-83-H7. Subclass specification of serum anti-VSPH7 IgG demonstrated THelper 2-cell dependent IgG1- and/or IgG2b-type antibody production. No significant THelper 1-cell dependent IgG2a-type anti-VSPH7 antibody production was detected in infected or in vaccinated animals. Taken together, these data indicate a strong intrinsic antigenicity of VSPH7, which stimulates a THelper 2-cell pathway of the murine immune system, independent of the route of antigen administration. Furthermore, the high immunostimulatory potential of the recombinant Salmonella/VSPH7 model vaccine suggests application of LT2M1C as an enteric biocarrier for the identification of putative new target vaccines in giardiasis.

Animals↗
PubMed1997

Giardia lamblia variant surface protein H7 stimulates a heterogeneous repertoire of antibodies displaying differential cytological effects on the parasite.

Previous investigations had shown that the Giardia lamblia clone GS/M-83-H7-specific variant surface protein (VSP) H7 consists of at least two antigenically distinct parts: (i) a variable 314-aa N-terminal region which contains one, or more, variant-specific epitopes eliciting a transient and consequently low-level antibody response preferentially detectable during the early phase of G. lamblia infection in mice; and (ii) a 171-aa C-terminal region which contains relatively conserved epitope(s) causing a persistent and consequently high-level antibody response during the later phase of an infection. The present study indicated that monoclonal antibody G10/4 and polyclonal antibodies from early-phase infected or hyperimmunized mice, directed against the variant-specific N-terminal regional exclusively recognized conformational cysteine-containing epitopes. These antibodies caused detachment and aggregation of trophozoites, and exhibited complement-independent cytotoxic effect towards the parasite. In contrast, polyclonal antibodies from late-phase infected mice, directed against the semi-conserved peptidyl structures in the C-terminal region, preferentially reacted with non-conformational epitopes. Such antibodies had no cytotoxic effect, but provoked parasite-detachment and -aggregation. These findings indicated that infection of mice with G. lamblia clone GS/M-83-H7 generates a heterogeneous repertoire of cytologically active anti-VSP antibodies which may have a direct influence on the course of the parasite infection.

Animals↗
PubMed1997

Characterization of a cDNA-clone encoding Nc-p43, a major Neospora caninum tachyzoite surface protein.

Neospora caninum is an apicomplexan parasite of veterinary importance which invades many different cell types and tissues. N. caninum tachyzoites proliferate intracellularly by endodyogeny. Eventually the massive proliferation of tachyzoites leads to host cell lysis and the newly formed parasites are released and invade neighbouring cells. Tachyzoite cell surface molecules could serve as ligands, mediating host cell adhesion and invasion. Nc-p43 is a recently identified N. caninum tachyzoite surface protein which is functionally involved in the processes leading to host cell invasion in vitro. Affinity-purified antibodies directed against Nc-p43 were used to screen a lambda gt22A-cDNA expression library constructed from N. caninum tachyzoites. The cDNA insert of one immunoreactive clone was subcloned and expressed in E. coli as a poly-histidine fusion protein. The identity of the resulting recombinant antigen termed recNc-p43 was confirmed by immunoblotting, immunofluorescence and electron microscopy using affinity-purified antibodies. The sequence of the cDNA insert encoding recNc-p43 was determined. Analysis of the deduced amino acid sequence revealed that Nc-p43 exhibited similarity to SAG1 (p30) and SAG3 (p43), 2 major surface antigens of Toxoplasma gondii tachyzoites. These similarities were not reflected on the immunochemical level, since no cross-antigenicity between SAG1, SAG3 and Nc-p43 was observed.

Amino Acid Sequence↗
PubMed1997

BBReader: a computer program for the combined use of the BioMagResBank and PDB databases.

A computer program ('BBReader') was developed which performs an inverse search in the BioMagResBank database. Given (cross) peak positions of a protein, the program searches for atoms with matching chemical shifts and suggests possible assignments for user-specified homo- and heteronuclear one- to three-dimensional COSY- and NOESY-type experiments. It can handle 1H, 13C and 15N spectra. Distance information from PDB files can be utilized for filtering possible NOESY cross peak assignments.

Databases, Factual↗
PubMed1997

Leukocyte filtration of single-donor platelet units through an integrated filter system for the Fresenius AS 104 blood cell separator.

BACKGROUND AND OBJECTIVES: White cell depletion of platelet concentrates is widely applied to reduce the incidence of transfusion complications. We investigated a new plateletpheresis kit with an integrated filter for leukocyte depletion of platelets. MATERIALS AND METHODS: Parameters of product quality were investigated before and after in-line filtration of 70 single-donor platelet (SDP) units obtained by apheresis. We studied three different filter batches manufactured for the Fresenius AS 104 blood cell separator, and evaluated different softwares and interface positions with respect to platelet (PLT) yield and white blood cell (WBC) contamination. RESULTS: PLT yields before and after filtration was not statistically different in the protocols studied. WBC contamination after WBC depletion was in the range of 10(4)/SDP unit. Glucose, lactate dehydrogenase, and the morphology score were not statistically different before and after filtration. CONCLUSIONS: In-line WBC filtration of SDP units sufficiently reduced WBC below 5 x 10(6)/unit. The study allowed definition of the filter composition and apheresis parameters to optimize PLT yield and minimize WBC contamination.

Filtration↗
PubMed1997

A multicenter evaluation of the routine use of a new white cell-reduction apheresis system for collection of platelets.

BACKGROUND: Residual white cells (WBCs) cause serious side effects in platelet transfusion. An in-line WBC-reduction system based on fluidized particle bed technology was recently developed as a modification of an existing plateletpheresis system. STUDY DESIGN AND METHODS: In an investigational phase, three flow profiles were evaluated using prototype software in five centers, each using their standard conditions. In the confirmatory phase, the released software was tested in three centers. WBCs were counted in two full Nageotte grids (dilution 1-in-5). RESULTS: With the prototype software, WBC levels were always below 1 x 10(6) per procedure (median, 25,000/procedure; n = 314). One profile proved to be superior to the other two with respect to platelet yield and residual WBCs, and it was incorporated in the released WBC-reduction system, together with a built-in process control. Median residual WBCs in these WBC-reduction system components not rejected by the process control were 19,000 per procedure (n = 211/225 total), with 99.5 percent of the platelet components having less than 1 x 10(6) WBCs. CONCLUSION: The protocol selected in the initial phase, now available as a WBC-reduction system, results in platelet concentrates with very low residual WBC levels. This satisfies even the most stringent criteria for WBC reduction in platelets, without the platelet loss typically seen with conventional fiber filtration.

Blood Platelets↗
PubMed1997

The Trypanosoma brucei autoantigen I/6 is an internally repetitive cytoskeletal protein.

Self-reactive host antibodies were shown earlier to exhibit strong and specific cross-reactivity to a particular trypanosomal antigen, protein I/6. The current study presents the molecular characterization of protein I/6. The major structural component of the cell body cytoskeleton of Trypanosoma brucei is a cagelike array of tightly connected microtubules which is in close contact to the overlaying cell membrane. Many of the unususal properties of the cytoskeleton of trypanosomes are due to the proteins associated with these microtubules. Protein I/6 was now shown to be a microtubule-associated protein, and it may be involved in crosslinking microtubules. Protein I/6 is coded for by a single gene, representing an exception rather than the rule for trypanosomal gene organization. From this single gene, two distinct mRNAs are generated through differential splicing. They differ in their polyadenylation sites, but both code for an identical polypeptide sequence of 33 kDa. Protein I/6 contains a non-functional EF-hand calcium binding domain and a domain of six tandemly arranged repeat units of eight amino acids length.

Amino Acid Sequence↗
PubMed1996

Polyglycylation of tubulin in the diplomonad Giardia lamblia, one of the oldest eukaryotes.

We have searched for post-translational modifications in tubulin of the diplomonad Giardia lamblia, which is a representative of the earliest branches in eukaryotic evolution. The carboxyterminal peptide of alpha-tubulin was isolated and characterized by automated sequencing and mass spectrometry. Some 60% of the peptide is unmodified, while the remainder shows various degrees of polyglycylation. The number of glycyl residues in the lateral side chain ranges from 2 to 23. All peptide species encountered end with alanine-tyrosine, indicating the absence of a detyrosination/tyrosination cycle. We conclude that tubulin-specific polyglycylation could be as old as tubulin and axonemal structures.

Amino Acid Sequence↗