PubMed Health⌕ Search

Biomedical subjects

S Maier

Publications and source records attributed to S Maier.

At least 55 records · Page 3Linked to original sources
PubMed1999

Primary structure, gene expression and chromosomal mapping of rodent homologs of the MEN1 tumor suppressor gene.

Mutations of the MEN1 tumor suppressor gene cause the multiple endocrine neoplasia type 1 (MEN1) syndrome in humans, and they are involved in a variety of sporadic human endocrine tumors. We here characterize the MEN1 gene homologs of the mouse and rat. cDNA was isolated from a mouse phage library, and two alternative MEN1 mRNA transcripts containing variant 5' untranslated regions were identified by RT-PCR in several mouse and rat tissues. When compared to the human molecule, mouse and rat MEN1 (611 and 610 amino acids, respectively) show an overall identity of 96.5% and 97.0% at the protein level, delimiting four conservational domains (A-D). Mouse and rat MEN1 mRNA, as studied by template-calibrated quantitative RT-PCR, is non-exclusively expressed in hematopoietic and endocrine cells, with similar expression patterns found in fetal and adult tissues. Fluorescent in situ hybridization maps the single murine MEN1 locus to chromosome 19, region B. No MEN1 gene mutations were identified in endocrine islet tumor cell lines RIN 5AH (rat) and NIT-1 (mouse) as compared to wild type cDNA. Our data define mouse and rat MEN1 as widely expressed and highly conserved homologs of the human MEN1 tumor suppressor gene whose role in biology and endocrine tumorigenesis is due for experimental study.

Animals↗
PubMed1999

Insulin stimulates the L-type Ca2+ current in rat cardiac myocytes.

OBJECTIVE: The aim was to study the L-type calcium current (ICa,L) in cardiac myocytes as a possible target of insulin in the regulation of cardiac function. METHOD: Using the whole-cell configuration of the patch-clamp technique, we investigated the stimulation of ICa,L by insulin in isolated rat ventricular myocytes. RESULTS: The stimulation of ICa,L by insulin was dose-dependent (EC50 = 33 nM) and reversible. Maximum stimulation of ICa,L over basal ICa,L was 86 +/- 11% (n = 25) at 1 microM insulin. Insulin (1 microM) shifted the current-voltage relationship and potential-dependent availability of ICa,L to more negative potentials by about 3.5 and 1.5 mV, respectively. The maximum conductance of ICa,L was increased by 1 microM insulin, from 26 +/- 4 to 39 +/- 5 nS (n = 11). Isoproterenol (100 nM), which stimulated ICa,L by 156 +/- 23% (n = 10) over basal ICa,L, acted faster than insulin. The half-maximum stimulation of ICa,L by isoproterenol and insulin was reached after 44 +/- 5 and 80 +/- 9 s, respectively. Insulin and isoproterenol responses were not additive. Insulin (1 microM) and isoproterenol (100 nM) stimulation of ICa,L was inhibited by Rp-cAMPS (1 mM) to 12 +/- 3 and 32 +/- 4%, respectively. Insulin (1 microM) increased cAMP content in rat cardiomyocytes by about two-fold. Insulin-like growth factor-1 (IGF-1; 5 microM) increased ICa,L by only 5.9 +/- 0.9% (n = 6). CONCLUSIONS: Our data show that insulin stimulates the L-type calcium current in isolated rat ventricular myocytes in a dose-dependent and reversible manner and suggest that this effect is mediated by insulin receptors and the cAMP-dependent protein kinase.

Adrenergic beta-Agonists↗
PubMed1999

Stimulation of L-type Ca2+ current in human atrial myocytes by insulin.

OBJECTIVE: The L-type calcium current (ICa,L) in isolated human atrial myocytes was investigated as a possible target of insulin in the regulation of cardiac function. METHODS: Atrial myocytes were obtained from patients undergoing cardiac surgery. Using the whole-cell configuration of the patch-clamp technique, we investigated the stimulation of ICa,L by insulin in single human atrial myocytes. RESULTS: We found a dose-dependent stimulation of ICa,L by insulin at concentrations of 100 nM, 1 microM and 10 microM. Maximum stimulation of ICa,L over basal ICa,L was 140 +/- 12% (n = 11) at 10 microM insulin. The maximum conductance of ICa,L was increased by 10 microM insulin from 4.0 +/- 0.3 nS to 8.3 +/- 1.0 nS (n = 6). The stimulation of ICa,L by insulin was dose-dependent and reversible. Isoproterenol (10 nM) that stimulates ICa,L by 271 +/- 48% (n = 10) over basal ICa,L acted faster than insulin. The half-maximum stimulation of ICa,L by isoproterenol and insulin (10 microM) was reached after 31 +/- 2 s and 52 +/- 5 s, respectively. The insulin effect shown was totally reversed by acetylcholine (3 microM) which is known to inhibit adenylyl cyclase activity/cAMP-production via Gi-proteins. Also, the selective insulin receptor tyrosine kinase inhibitor (hydroxy-2-naphthanelyl-methyl)phosphonic acid completely inhibited the insulin induced effect. CONCLUSION: Our data show that insulin stimulates the L-type calcium current in isolated human atrial myocytes in a dose-dependent and reversible manner which appears to involve the insulin receptor tyrosine kinase. Insulin regulation of ICa,L in human atrial myocytes may be an interesting system for the analysis of the metabolic syndrome in man.

Acetylcholine↗
PubMed1999

Detection of soluble HLA-G molecules in plasma and amniotic fluid.

Although the cDNA sequence of HLA-G antigens is compatible with their expression as soluble molecules (sHLA-G), the determination of native sHLA-G levels in body fluids has not yet been described. The lack of this information is likely to reflect the difficulties in developing an assay suitable to measure sHLA-G antigens in the presence of soluble HLA-A, -B and -C (sHLA-I) antigens, since most of the available anti-HLA-G mAb do not detect soluble beta2-m associated HLA-G antigens or crossreact with sHLA-I antigens. Therefore, we have developed a two-step assay which eliminates the interference of classical HLA class I antigens. In the first step, the sample is depleted of sHLA-I antigens and of HLA-E antigens with mAb TP25.99. Then, HLA-G antigens are captured with mAb W6/32 and detected with anti-beta2-m mAb in ELISA. Utilizing this assay, sHLA-G antigen levels were measured in EDTA plasma from 92 controls with known HLA types, 28 women at delivery and the corresponding cord bloods and in 50 amniotic fluids. Mean sHLA-G plasma levels did not differ between males (24.9+/-3.0 SEM ng/ml; n=42) and females (20.1+/-2.1 SEM ng/ml; n = 50). However, sHLA-G levels in HLA-A11 positive probands (mean: 13.0+/-4.4 SEM ng/ml; n=12) were significantly (P<0.05) lower than in HLA-A11 negative ones (mean: 24.5+/-2.0 SEM ng/ml; n=80). sHLA-G levels in women at delivery (mean: 22.9+/-2.2 SEM ng/ml; n=28) were in the range of controls but were significantly (P<0.001) reduced in the corresponding cord bloods (mean: 13.8+/-1.5 SEM ng/ml; n=28). sHLA-G levels in amniotic fluids (mean: 15.5 + 1.0 SEM ng/ml; n=50) were significantly (P<0.001) lower than in plasma. sHLA-G levels were 5 and 11% of those of sHLA-I antigens in plasmas and amniotic fluids, respectively. Individual sHLA-G levels were not correlated with sHLA-I levels. SDS-PAGE analysis of plasma sHLA-G antigens revealed two molecular variants with a 35 kD and a 27 kD MW corresponding to the sizes of sHLA-G1 and -G2 isoforms. In conclusion, our study has shown that the two-step assay we have developed is reliable in measuring sHLA-G antigen levels. This assay will facilitate the analysis of the biological and clinical significance of sHLA-G antigens in plasma.

Adult↗
PubMed1998

Importance of T cells to accelerated rejection and acceptance of renal allografts in sensitized rat recipients.

BACKGROUND: Sensitized recipients often experience fulminant allograft loss by yet ill-defined cellular and/or humoral immune mechanisms. In this study, we analyzed the contribution of cellular elements, in particular T cells, to the accelerated rejection of renal allografts in sensitized rats. METHODS AND RESULTS: LEW rats sensitized with BN skin grafts died of uremia in 3.3+/-0.9 days after transplantation of a BN kidney, similarly to bilaterally nephrectomized animals. Adoptive transfer of 10(6) graft-infiltrating mononuclear cells as well as their CD25+ subset into otherwise normal LEW recipients accelerated rejection of BN test cardiac allografts (5.4+/-0.5 days to 6.6+/-0.4 days vs. 7.8+/-0.8 days in controls, P<0.0007), while the CD25- population was ineffective (8.0+/-0.6 days, NS). Furthermore, alpha/beta-T-cell receptor (TCR)-targeted therapy with R73 monoclonal antibody abrogated accelerated rejection, and produced long-term survival in sensitized animals treated before kidney engraftment (day -7 to day -1). Long-term survival was associated with an up-regulation of intragraft interleukin-4 and interleukin-10 expression in conjunction with depressed Th-1-type cytokines. In addition, alpha/beta-TCR-targeted therapy even in low subtherapeutic dose decreased IgM alloantibody levels, and prevented the switch from IgM to IgG alloantibody response. CONCLUSIONS: This is the first report that documents the striking efficacy of alpha/beta-TCR-targeted therapy in sensitized rat renal transplant recipients. The results provide evidence for a critical role of T cells for both accelerated rejection and long-term graft survival. Up-regulation of Th2-type cytokine profile may, at least in part, contribute to the acquisition of immune unresponsiveness after alpha/beta-TCR-targeted therapy in this well-defined rat renal transplant model.

Adoptive Transfer↗
PubMed1998

Right hemisphere activation during indirect semantic priming: evidence from event-related potentials.

Healthy subjects performed a lexical decision task in a semantic priming paradigm while event-related potentials (ERPs) were recorded from 64 channels. Semantic distance between prime and target was varied by including directly, indirectly, and nonrelated word pairs. At centro-parietal electrodes an N400 to nonrelated pairs was elicited bilaterally which was sensitive only to direct, but not to indirect semantic priming. These N400 priming effects were mirrored by the RT data. At inferior fronto-temporal sites directly related words showed ERP priming effects over both hemispheres. However, indirectly related words only elicited ERP priming effects over the right hemisphere. These results support the hypothesis that the right hemisphere semantic system is involved in processing of remote semantic information.

Adult↗
PubMed1998

[Functional magnetic resonance tomography in psychopathological research].

Mental disorders are characterised by psychopathological symptoms which correspond to functional brain states. Functional magnetic resonance imaging (fMRI) is used for the non-invasive study of cerebral activation patterns in man. First of all, the neurobiological principles and presuppositions of the method are outlined. Results from the Heidelberg imaging lab on several simple sensorimotor tasks as well as higher cognitive functions, such as working and semantic memory, are then presented. Thereafter, results from preliminary fMRI studies of psychopathological symptoms are discussed, with emphasis on hallucinations, psychomotoric phenomena, emotions, as well as obsessions and compulsions. Functional MRI is limited by the physics underlying the method, as well as by practical constraints regarding its use in conjunction with mentally ill patients. Within this framework, the problems of signal-to-noise ratio, data analysis strategies, motion correction, and neurovascular coupling are considered. Because of the rapid development of the field of fMRI, maps of higher cognitive functions and their respective pathology seem to be coming within easy reach.

Brain↗
PubMed1998

Non-fatal mirtazapine overdose.

We report the case of intoxication of a 41-year-old female patient suffering from major depression with mirtazapine complicated by severe hypothermia. The patient was brought to an intensive care unit 10 hours after intake of 1200 mg mirtazapine and 20 mg lorazepam and laying outside at outdoor temperatures below 0 degree C. The mirtazapine plasma-level was 368 ng/ml still after 41 hours. Body temperature was reduced to 26 degrees C and rhabdomyolysis due to hypothermia was observed. Cardial and respiratory function was compromised and intubation was necessary. The patient recovered without persisting somatic impairment.

Adult↗
PubMed1998

Lateralised semantic and indirect semantic priming effects in people with schizophrenia.

BACKGROUND: In schizophrenia, disturbances in the development of physiological hemisphere asymmetry are assumed to play a pathogenetic role. The most striking difference between hemispheres is in language processing. The left hemisphere is superior in the use of syntactic or semantic information, whereas the right hemisphere uses contextual information more effectively. METHOD: Using psycholinguistic experimental techniques, semantic associations were examined in 38 control subjects, 24 non-thought-disordered and 16 thought-disordered people with schizophrenia, for both hemispheres separately. RESULTS: Direct semantic priming did not differ between the hemispheres in any of the groups. Only thought-disordered people showed significant indirect semantic priming in the left hemisphere. CONCLUSIONS: The results support: (a) a prominent role of the right hemisphere for remote associations; (b) enhanced spreading of semantic associations in thought-disordered subjects; and (c) disorganisation of the functional asymmetry of semantic processing in thought-disordered subjects.

Analysis of Variance↗
PubMed1998

Frontal brain asymmetry and affective style: a conceptual replication.

Recent studies have demonstrated that positive and negative affective reactivity can be predicted by resting electroencephalographic (EEG) asymmetry in frontal brain regions. These studies used different methods to assess asymmetry and affectivity. The goal of the present study was a conceptual replication of these results and to investigate their independence of employed procedures. Resting EEG of 37 subjects was recorded and affective slides were presented to obtain ratings of subjects' emotional reactions. Different procedures were applied to the data to assess the relation between asymmetries and affective reactivity. Depending on the particular analysis procedure, there were associations between anterior asymmetry and affectivity in line with the published findings, opponent to those findings, or no relation between anterior asymmetry and affective reactivity.

Adult↗
PubMed1997

Complex expression pattern of the TNF region gene LST1 through differential regulation, initiation, and alternative splicing.

Recently, a novel gene, LST1, was identified in the tumor necrosis factor region of the HLA complex, 4 kb centromeric of the lymphotoxin beta gene. By analyzing several full-length cDNA clones and the genomic DNA, we identified seven exons and four introns, spanning 2.7 kb. Isolation of mouse LST1 cDNA clones established the open reading frame. LST1 transcription is characterized by four alternative transcription initiation sites and extensive alternative splicing. The derived polypeptides vary with regard to the presence of the hydrophobic N-terminus and in short internal sequences. In addition, alternative splicing results in LST1 mRNAs encoding different carboxy-terminal sequences. LST1 is predominantly transcribed in monocytes, and mRNA levels increase upon stimulation with interferon-gamma, with a concomitant change in the mRNA pattern resulting in an enhanced expression of the short LST1 transcripts. These data suggest that LST1 may have a specific role in monocytes and possibly also in T cells. Moreover, we found that the recently published cDNA 1C7 is encoded just centromeric of LST1.

Alternative Splicing↗
PubMed1997

Left lateralized P300 amplitude deficit in schizophrenic patients depends on pitch disparity.

The general reduction of P300 amplitude in response to auditory oddball stimuli is one of the most consistently replicated biological observations in schizophrenic patients. Several groups have reported a P300 asymmetry in schizophrenic patients, others have not been able to replicate this finding. In order to clarify this issue, we examined the effect of stimulus discriminability on P300 amplitude distribution in schizophrenic patients and in age-matched normal control subjects, using two different auditory oddball paradigms. The detection of the target tone was either simple or difficult, due to manipulation of pitch disparity. The P300 amplitude was comparatively smaller in the schizophrenic patient group compared to the healthy controls and in the difficult task compared to the simple. The schizophrenic patients showed a specific P300 amplitude reduction over left temporal electrode sites when the simple paradigm was used. The difficult paradigm did not elicit asymmetrical P300 amplitudes in schizophrenic patients.

Adult↗
PubMed1997

[Event-related potentials in semantic speech processing by schizophrenic patients].

Event-related potentials (ERPs) can be used for high-resolution mental chronometry. For about 15 years, this method has been applied to the study of linguistic phenomena. Semantic incongruency produces a negative component at about 400 ms after stimulus onset, the N400. We measured the N400 component in 20 schizophrenic patients and 20 normal control subjects performing a lexical decision task in which semantic distance between prime and target was varied. The results provide evidence of dysfunctional semantic information processing in schizophrenic patients, and reaction time data from previous studies can be interpreted within an electrophysiological framework. The N400 amplitude and latency data support recent spreading activation models of schizophrenic language dysfunction.

Adult↗
PubMed1997

[Transurethral collagen injection for treatment of urinary stress incontinence].

Minimally invasive treatment of urinary incontinence has become a subject of major interest in recent years. We examined the use of transurethral collagen injection for incontinence treatment. A total of 48 patients were selected for this procedure from April 1993 to February 1997-26 male patients (19 post-RPX incontinence and 7 post-TUR incontinence) and 22 female patients (all after previous incontinence surgery) were treated by injection of collagen into the continence region. The whole group underwent an average of 1.8 sessions, and a mean collagen injection volume of 14.5 ml was delivered per session. Mean follow-up was 9.2 months. Of the female population, 68.2% were cured or greatly improved. In the male population only 47.3% of the post-RPX patients and 6/7 of the post-TUR patients benefited from the procedure. In males, treatment outcome depends on the degree of pretreatment incontinence, because all grade III incontinence patients did worse. Therefore we conclude: transurethral collagen injection is an interesting method in the treatment of urinary incontinence if proper patient selection is assured.

Aged↗
PubMed1997

[Event related potentials and emotional pictures:effect of stimulus presentation time].

The perception of the emotional content of a stimulus is a preattentive automatic process which causes an emotional reaction. As the ongoing stream of behavior might be disturbed by the emotional reaction, a controlled process is initialited at the same time, which normally leads to an inhibition of the emotional response. By means of event related potentials it should be possible to observe these controlled processes. In a first study using photographs from the International Affective Picture System, Diedrich et al. (1997) reported enhanded P300 amplitudes for emotional stimuli, even when the task distracted from the emotional content of the stimuli. This was interpreted as an index of the additional, controlled information processing elicited by the emotional content of the stimuli. Additionally, Diedrich et al. observed a frontel slow positivity, which might indicate the inhibition of the emotional response. However, this frontal slow wave might also be explained by the stimulus presentation time, which lasted 500 ms. This study is a conceptual replication of the experiment of Diedrich et al. Stimulus presentation time of neutral and emotional slides was varied in three steps (250 ms, 500 ms and 2000 ms). Subjects either performed a structural or an emotion-focused task on the stimuli. The results for the P300 component were exactly replicated. However, the variation of slow frontal positivity differed from that in the first study. Differences in the intensity of the emotional stimuli are discussed as a reason für this result.

Adult↗