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Biomedical subjects

S Maier

Publications and source records attributed to S Maier.

At least 37 records · Page 2Linked to original sources
PubMed2002

[The sympathetic axons of the nerves of the hand].

PURPOSE: In the hand surgery literature, more and more studies seem to indicate that the number of sympathetic fibers in the median and the ulnar nerves varies. However, there are no studies that confirm this suspicion. METHOD AND MATERIAL: Six hours post mortem samples were taken from the median and ulnar nerves, the superficial branch of the radial nerve, and from all digital nerves (each five females and males, average age 78 years). 13 samples were taken from one hand. To make sympathetic fibers visible, the immunohistochemical staining technique with tyrosinhydroxylase (TH) antibodies was used. Quantitative assessment of the sympathetic axons was made in whole cross-sections of the nerve. Statistical evaluation was performed with Wilcoxon rank-sum tests. RESULTS: The TH-positive axons are arranged in groups and are located in the endoneurium. No isolated sympathetic fibers were found in the peri- and epineurium. TH-positive axons were present on the arterial walls including the smallest arterioles. Proximal to the wrist, the median nerve has more sympathetic fibers than the ulnar nerve. The number, however, of the fibers was the same in each fascicle. A comparison of the digital nerves shows significant differences only between the radial nerve of the thumb and the ulnar nerve of the ring finger and between the radial nerve of the index finger and the ulnar nerve of the little finger. CONCLUSION: Although the median nerve proximal to the wrist has on average 20 fascicles and the ulnar nerve only 14, the number of fibres in each fascicle is the same. Therefore, based on the present study we conclude that there is no significant difference in the sympathetic fiber distribution of the two nerves.

Adrenergic Fibers↗
PubMed2002

Effects of the hallucinogen psilocybin on covert orienting of visual attention in humans.

Hallucinogenic drug-induced states are considered as models for acute schizophrenic disorders (experimental psychoses). In a double-blind study with healthy volunteers we investigated the influence of the serotonergic hallucinogen psilocybin, the ecstasy-like drug 3,4-methylenedioxyethylamphetamine (MDE), the stimulant d- methamphetamine and placebo on covert orienting of spatial attention (n = 8 in each group). Reaction times were prolonged after ingestion of psilocybin > MDE, but not after d-methamphetamine. In addition, subjects on psilocybin exhibited particularly slow reaction times in invalid trials at short cue target intervals and failure of response inhibition in valid trials at long cue target intervals for right visual field targets. Despite some methodological limitations, these results are in line with both bilateral impairment of disengagement of attention and a lateralized impairment of inhibition of return (IOR) in productive psychotic states. Additional investigations with larger samples, different hallucinogenic substances (serotonergic agonists vs. NMDA antagonists) and different dose regimens are needed in order to further explore the suggested relationship between visuospatial attentional dysfunction and acute psychotic conditions.

3,4-Methylenedioxyamphetamine↗
PubMed2002

Consensus statements from the Second International Lung Cancer Molecular Biomarkers Workshop: a European strategy for developing lung cancer molecular diagnostics in high risk populations.

The Second Molecular Biomarkers Workshop was held at the Roy Castle International Centre for Lung Cancer Research in Liverpool, in June 2001 and it brought together experts in the clinical, epidemiological and molecular-pathology of lung cancer from Europe and the USA, to address issues surrounding the development of a European strategy for early lung cancer detection. The 2001 Workshop Breakout Groups concentrated on the current challenges in the early detection of lung cancer which need to be addressed in the light of the recent surge in interest in many countries for mounting new clinical trials to evaluate the utility of Spiral CT in early lung cancer detection. If population-based trials of CT screening are mounted it will also be a favorable clinical environment in which to evaluate efficiently recent advances in molecular screening and genotyping. The Workshop focused specifically on: a) clinical and molecular biomarkers, b) sputum as an early detection and diagnostic tool, c) validation of molecular markers prior to their use in early detection trials and d) ethical issues that have to be considered in early lung cancer detection trials. A distillation of the Workshop discussions is given in this article.

Biomarkers, Tumor↗
PubMed2002

Epigenomics: genome-wide study of methylation phenomena.

Epigenetics is one of the key areas of future research that can elucidate how genomes work. It combines genetics and the environment to address complex biological systems such as the plasticity of our genome. While all nucleated human cells carry the same genome, they express different genes at different times. Much of this is governed by epigenetic changes resulting in differential methylation of our genome--or different epigenomes. Individual studies over the past decades have already established the involvement of DNA methylation in imprinting, gene regulation, chromatin structure, genome stability and disease, especially cancer. Now, in the wake of the Human Genome Project (HGP), epigenetic phenomena can be studied genome-wide and are giving rise to a new field, epigenomics. Here, we review the current and future potential of this field and introduce the pilot study towards the Human Epigenome Project (HEP).

Autoimmune Diseases↗
PubMed2001

Critical role of Kupffer cell-derived IL-10 for host defense in septic peritonitis.

Intra-abdominal infection in patients following major visceral surgery is associated with high mortality. Using a macrophage depletion technique, we demonstrate that in murine septic peritonitis, Kupffer cells are a major source of systemic IL-10 levels. Kupffer cell-depleted mice were highly susceptible to the lethal effects of septic peritonitis and exhibited an increased bacterial load. Kupffer cell-depleted mice were protected by the administration of an IL-10-Fc fusion protein. Loss of Kupffer cell-derived IL-10 was associated with a weak increase in serum IL-12 levels, whereas TNF, IL-1alpha, and IL-18 levels were not significantly elevated, suggesting that the loss of Kupffer cell-derived IL-10 did not result in a toxic cytokine release syndrome. Instead, loss of Kupffer cell-derived IL-10 was associated with a reduced splenocyte production of IFN-gamma that is required for immune protection in murine septic peritonitis. Therefore, the results suggest that the protective function of IL-10 in septic peritonitis may not be restricted to the anti-inflammatory activities of IL-10.

Animals↗
PubMed2001

Inhibition of natural killer cells results in acceptance of cardiac allografts in CD28-/- mice.

Successful transplantation of allogeneic organs is an important objective in modern medicine. However, sophisticated immune defense mechanisms, primarily evolved to combat infections, often work against medical transplantation. To investigate the roles of natural and adaptive immune responses in transplant rejection, we functionally inactivated key effector systems of the innate (NK cells) and the adaptive immune system (CD28-mediated costimulation of T cells) in mice. Neither of these interventions alone led to acceptance of allogeneic vascularized cardiac grafts. In contrast, inhibition of NK-receptor-bearing cells combined with CD28-costimulation blockade established long-term graft acceptance. These results indicate a concerted interplay between innate and adaptive immune surveillance for graft rejection. Thus we suggest that inactivation of NK-receptor-bearing cells could be a new strategy for successful survival of solid-organ transplants.

Animals↗
PubMed2001

[Diagnosis of vesico-intestinal fistulas by contrast medium enhanced 3-D ultrasound].

AIM: Standard diagnostic tools for vesico-intestinal fistulas are cystoscopy, cystography, colonoscopy, and contrast enema. The aim of our study was to evaluate the efficacy of transrectal 3D-ultrasound with contrast media in these patients. METHOD: From 5/98 to 12/99 we examined 10 patients with symptoms of a vesico-intestinal fistula (pneumaturia, faecaluria). After placement of a transurethral catheter a transabdominal ultrasound examination (Kretz Combison 530) was performed with the bladder half full to evaluate the bladder wall. Then the bladder was filled with diluted ultrasound contrast media (Levovist 40 mg/ml) to visualize the flow from the bladder towards the fistula. To verify a flow through the bladder wall a colour Doppler sonography of the region of interest was added. To evaluate form and extent of the fistula a transrectal ultrasound with 3D-image assessment was performed. RESULTS: Using this technique it was possible to demonstrate a vesico-intestinal fistula in 9 of 10 patients. In all cases these findings were confirmed by the standard diagnostic procedures. The fistulas were caused by: bladder carcinoma (n = 1), carcinoma of the colon (n = 2), Crohn's disease (n = 3) and diverticulitis of the sigma (n = 3). One patient presented with a neovesico-intestinal fistula in an irradiated local recurrence of bladder carcinoma. In one patient with Crohn's disease whose only symptom was pneumaturia all diagnostic tools failed to provide the diagnosis. CONCLUSION: For the first time vesico-intestinal fistulas could be demonstrated by ultrasound with 3D-image assessment using contrast media. This technique might be an effective addition to the standard diagnostics of vesico-intestinal fistulas reducing the exposure to radiation.

Contrast Media↗
PubMed2000

Tributyrin induces differentiation, growth arrest and apoptosis in androgen-sensitive and androgen-resistant human prostate cancer cell lines.

Progression to androgen independence remains the main problem that impacts on survival and quality of life in prostate cancer patients. We have investigated the potency of tributyrin, an orally available prodrug of butyrate, to induce growth arrest, differentiation and apoptosis in LNCaP, PC-3 and TSU-PR1 human prostate cancer cell lines. Cells were treated with 0.1 to 5 mM tributyrin or sodium butyrate. Growth inhibition, cell cycle arrest and apoptosis induction was assessed using standard methods. Both agents induced a more differentiated, fibroblast-like phenotype in androgen-sensitive as well as androgen-resistant cell lines. Expression of prostate-specific antigen was increased in LNCaP cells by tributyrin as a indicator of differentiation. The IC(50) for sodium butyrate was 2.5 mM in PC-3 and TSU-PR1 cells. LNCaP cells exhibited <50% growth inhibition at 5 mM sodium butyrate. However, the IC(50) for tributyrin was 0.8 mM in PC-3 cells, 1.2 mM in TSU-PR1 cells and 3.1 mM in LNCaP cells. Flow cytometry revealed a strong G1-arrest after exposure to tributyrin or sodium butyrate. Both agents resulted in a strong increase of apoptosis rates compared with mock-treated cells. Overall, tributyrin had a 2.5- to 3-fold growth inhibitory and apoptosis-inducing potency compared with equimolar concentrations of sodium butyrate. Our results demonstrate that tributyrin is more potent than butyrate in regard to cell growth inhibition and apoptosis induction at pharmacologically relevant concentrations. Hence, tributyrin may be a promising candidate for clinical protocols in prostate cancer.

Androgens↗
PubMed2000

Role of the MEN1 tumour suppressor gene in human ductal pancreatic cancer.

MEN1 is a novel tumour suppressor gene involved in the etiology of sporadic endocrine pancreatic tumours. Based on common ontogenetic features of both tissues, we analyzed the role of MEN1 in ductal pancreatic cancer. Wild type MEN1 mRNA expression, but no mutations within the MEN1 coding sequence or MEN1 promoter region were detected in human pancreatic adenocarcinoma tissues and carcinoma cell lines, using sensitive single-strand conformational polymorphism-heteroduplex and sequencing analyses. Thus, human pancreatic cancer does not seem to require inactivation of the MEN1 tumour suppressor pathway.

Carcinoma, Ductal, Breast↗
PubMed2000

Implications of HLA-E allele expression and different HLA-E ligand diversity for the regulation of NK cells.

The interaction of HLA-E with CD94/NKG2A is dependant on the binding of HLA class I signal sequence derived peptides to HLA-E. In the caucasoid population two HLA-E alleles are observed at equal frequencies. Here we study the functional differences between the two HLA-E molecules with regard to cell surface expression, peptide binding, and potential to inhibit lytic activity of a CD94/NKG2A(+) NK cell line. In contrast to the HLA-E(R) allele, the HLA-E(G) allele shows considerable cell surface expression even in the absence of endogenous HLA class I signal sequence derived HLA-E ligands. Eighteen HLA-E allele/HLA-E ligand combinations were analyzed. No correlation between cell surface expression of HLA-E and NK cell inhibition was observed. The peptides present in the signal sequences of HLA-B15, -Cw0402, and -Cw7 bound to both HLA-E alleles but did not lead to an inhibition of NK cell lysis. In our experimental system the peptides A2 and G were not effective with regard to NK cell inhibition when bound to the HLA-E(R) allele. These results may be of functional significance particularly in the placenta where the only HLA-E ligands are derived from HLA-G and -C.

Alleles↗
PubMed2000

Sepsis after major visceral surgery is associated with sustained and interferon-gamma-resistant defects of monocyte cytokine production.

BACKGROUND: Recent clinical trials failed to demonstrate beneficial effects of anti-inflammatory sepsis therapy. The present study therefore asked the following questions: Is there evidence for immunosuppression during postoperative sepsis? When, during the septic course, may immunosuppression develop? Can defective cellular functions be restored by in vitro treatment with interferon-gamma (IFN-gamma)? METHODS: The study included 35 patients with sepsis after major visceral surgery and 85 control patients. Monocyte secretion of interleukin (IL)-1 beta, IL-12 p40 and p70, IL-18, tumor necrosing factor, and IL-10 with or without IFN-gamma treatment and its correlation with the course and outcome of postoperative sepsis were determined. RESULTS: Postoperative sepsis was associated with an immediate defect of endotoxin-stimulated monocyte production of IL-12 p40, IL-1 beta, and IL-10 in both surviving and nonsurviving patients. During the final phase of postoperative sepsis, a significant recovery of IL-12 p40 and IL-1 beta secretion, but not of IL-10 production, correlated with survival. Despite the exposure of monocytes in vitro to IFN-gamma for 16 hours, the production of the biologically active IL-12 p70 heterodimer was severely suppressed both in survivors and nonsurvivors, although the secretion of the p40 subunit was restored. In contrast, IFN-gamma treatment resulted in a significant suppression of monocyte IL-1 beta production in all patient subgroups. Alterations of monocyte tumor necrosing factor secretion were not observed. The production of IL-18 was below the limits of detection in all samples. CONCLUSIONS: Postoperative sepsis was associated with immediate monocyte defects that affected both pro- and anti-inflammatory cytokine secretion, which suggests that immunosuppression is a primary rather than a compensatory response to a septic challenge. Sepsis survival correlated with the recovery of the proinflammatory, but not the anti-inflammatory, response. The treatment of monocytes with IFN-gamma did not reconstitute defective proinflammatory cytokine production.

Cytokines↗
PubMed2000

Massive chemokine transcription in acute renal failure due to polymicrobial sepsis.

Abdominal sepsis and septic shock are still major causes of mortality in intensive care units (ICU). Acute renal failure (ARF) is one of the hallmarks encountered in septic shock. The pathophysiological alterations leading to ARF are poorly understood. A novel murine model of polymicrobial sepsis (colon ascendens stent peritonitis [CASP]) was used to investigate functional renal parameters, renal chemokine transcription levels, and recruitment of inflammatory leukocytes in septic ARF. CASP was induced by inserting a 14-gauge stent into the colon ascendens of C57BL/6 mice, generating a septic focus resulting in polymicrobial sepsis. Mice were monitored for urine output and serum azotemia. Kidneys were harvested for analysis of leukocyte infiltration by immunohistochemistry and chemokine gene expression by RNase protection assay (3, 6, 12, and 18 h). CASP, but not sham-CASP, resulted in anuria immediately after surgery and in elevated serum creatinine and BUN detected 18 h after CASP surgery, confirming acute renal failure. Progressive induction of chemokine gene expression was observed for IP-10, MIP-2, MIP-1alpha, MIP-1beta, MCP-1, and RANTES peaking at 12 h with subsequent decrease. Immunohistochemistry revealed an accumulation of neutrophils and monocytes which had adhered to the renal vascular endothelium. Thus, acute renal failure in sepsis is accompanied by a marked upregulation of chemokines of the CC and CXC group within the kidney.

Acute Kidney Injury↗
PubMed2000

Genetic influence on laterality in schizophrenia? A twin study of neurological soft signs.

OBJECTIVE: This study explored the genetic basis of neurological soft signs in schizophrenia and addressed disturbed hemispheric lateralization. METHOD: The authors investigated neurological soft signs in 30 monozygotic twin pairs, 13 pairs discordant for schizophrenia or schizoaffective disorder and 17 healthy comparison twin pairs. RESULTS: The twins with schizophrenia showed higher total scores for neurological soft signs than did the comparison subjects. The total scores for neurological soft signs of the nonaffected discordant twins were significantly higher than those of the comparison twins. There was a significant difference between the nonaffected and affected discordant twins in total scores for neurological soft signs. In contrast to the comparison subjects, the nonaffected and affected twins of the discordant pairs showed a trend toward higher scores for neurological soft signs on the left body half. CONCLUSIONS: These results suggest that the occurrence of neurological soft signs and, more specifically, their lateralization to the left body half are genetically transmitted.

Adult↗
PubMed2000

Multiple endocrine neoplasia type 1 (MEN1) gene mutations in a subset of patients with sporadic and familial primary hyperparathyroidism target the coding sequence but spare the promoter region.

Germ line mutations of the multiple endocrine neoplasia type 1 (MEN1) tumour suppressor gene cause MEN1, a rare familial tumour syndrome associated with parathyroid hyperplasia, adenoma and hyperparathyroidism (HP). Here we investigated the role of the MEN1 gene in isolated sporadic and familial HP. Using RT-PCR single-strand conformational polymorphism screening, somatic (but not germ line) mutations of the MEN1 coding sequence were identified in 6 of 31 (19.3%) adenomas from patients with sporadic primary HP, but none in patients (n=16) with secondary HP due to chronic renal failure. MEN1 mutations were accompanied by a loss of heterozygosity (LOH) for the MEN1 locus on chromosome 11q13 in the adenomas as detected by microsatellite analysis. No DNA sequence divergence within the 5' region of the MEN1 gene, containing the putative MEN1 promoter, was detectable in HP adenomas. Clinical characteristics were not different in HP patients with or without MEN1 mutation. Heterozygous MEN1 gene polymorphisms were identified in 9.6% and 25% of patients with primary and secondary HP respectively. In a large kindred with familial isolated familial HP, MEN1 germ line mutation 249 del4 and LOH was associated with the HP phenotype and a predisposition to non-endocrine malignancies. We suggest that the bi-allelic somatic loss of MEN1 wild-type gene expression is involved in the pathogenesis of a clinically yet undefined subset of sporadic primary HP adenomas. MEN1 genotyping may further help define the familial hyperparathyroidism-MEN1 disease complex, but it seems dispensable in sporadic primary HP.

Adenoma↗
PubMed2000

Muscle fibers in inflammatory myopathies and cultured myoblasts express the nonclassical major histocompatibility antigen HLA-G.

We demonstrate that HLA-G, a nonclassical major histocompatibility complex class I antigen, is expressed in muscle fibers in various inflammatory myopathies. Further, interferon-gamma induces surface expression and upregulation of mRNA transcripts corresponding to different isoforms of HLA-G in myoblasts cultured from control subjects and patients. HLA-G may have important immunological functions in inflammatory myopathies and other local immune reactions as they occur during vaccination, myoblast transplantation, and gene therapy.

Cells, Cultured↗
PubMed1999

Electrophysiological correlates of direct versus indirect semantic priming in normal volunteers.

The N400 component of event related potentials (ERP) was studied in 27 right-handed healthy subjects in a speeded lexical decision task. The semantic distance between primes (always words) and targets (50% words, 50% non-words) was systematically varied. Prime-target relations included directly related words (hen-egg), indirectly related words (lemon-sweet), and non-related words (sofa-wing). ERPs were recorded from 20 scalp electrodes positioned according to the international 10-20 system. The N400 reflected semantic distance with the most negative and latest N400 peak in the non-related condition, the least negative and earliest N400 peak in the direct condition and the peak in the indirect condition in-between. Hence, N400 priming effect in the indirect condition was obtained in the absence of strong sentential constraints and even though the mediating word was physically not present.

Adult↗