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Biomedical subjects

M Wagner

Publications and source records attributed to M Wagner.

At least 19 recordsLinked to original sources
PubMed2000

The amyloid beta peptide abeta (25-35) induces apoptosis independent of p53.

Apoptosis of neuronal cells apparently plays a role in Alzheimer's disease (AD). The amyloid beta (Abeta) peptide derived from beta-amyloid precursor protein is found in AD brain in vivo and can induce apoptosis in vitro. While p53 accumulates in cells of AD brain, it is not known if p53 plays an active role in Abeta-induced apoptosis. We show here that inactivation of p53 in two experimental cell lines, either by expression of the papillomavirus E6 protein or by a shift to restrictive temperature, does not affect apoptosis induction by Abeta (25-35), indicating that Abeta induces apoptosis in a p53-independent manner.

Amyloid beta-Peptides↗
PubMed2000

The p44S10 locus, encoding a subunit of the proteasome regulatory particle, is amplified during progression of cutaneous malignant melanoma.

Gene amplification is frequently present in human tumors, although specific target genes relevant to many amplified loci remain unidentified. An expression cloning assay enabled identification of a candidate oncogene derived from human chromosome 3p14.1. The cDNA retrieved from morphologically transformed cells contained the full-length protein coding region and detected an abundant transcript in the same cells. Sequence analysis revealed identity with the wild-type sequence of p44S10, a highly conserved subunit of the 26S proteasome that exhibits similarity to the Arabidopsis fus6/cop11 family of signaling molecules. p44S10 gene copy number and mRNA expression were increased in association with segmental 1.8 - 11-fold chromosomal gains in cutaneous malignant melanoma cell lines (5/13; 40%) and tumors (2/40; 5%), and in breast cancer MCF-7 cells. Likewise, malignant progression of human radial growth phase WM35 melanoma cells was associated with amplification and increased expression of endogenous p44S10, and increased expression of p44S10 was sufficient to induce proliferation of WM35 cells in vivo. The results demonstrate segmental copy number gains within chromosome 3p in cutaneous malignant melanoma and suggest that deregulation of a proteasome regulatory particle subunit may contribute to the malignant phenotype.

Adenosine Triphosphatases↗
PubMed2000

Role of MT-MMPs and MMP-2 in pancreatic cancer progression.

Activation of matrix metalloproteinase-2 (MMP-2) by the membrane-type matrix metalloproteinases (MT-MMPs) has been associated with tumor progression. In the present study, we examined the role of MMP-2 and its activators MT1-MMP, MT2-MMP and MT3-MMP in pancreatic tumor cell invasion and the development of the desmoplastic reaction characteristic of pancreatic cancer tissues. Northern blot analyses revealed that transcript levels of MT1-MMP and MT2-MMP, but not MT3-MMP, were enhanced in pancreatic cancer tissues (n = 18) compared with both chronic pancreatitis (n = 9) and healthy pancreas (n = 9). A good correlation was found between MT1-MMP and both MMP-2 expression (p < 0.01) and activity in pancreatic cancer tissues. In addition, expression and activation of MMP-2 were strongly associated with the extent of the desmoplastic reaction in pancreatic cancer tissues. Invasion assays showed a good correlation between MMP-2 expression and activity and the invasive potential of pancreatic cancer cell lines. In cell lines with high levels of MMP-2 expression and activity, the MMP inhibitor Batimastat led to significant reduction of the number of invading cells. Our results suggest that MT1-MMP is involved in the progression of pancreatic cancer via activation of MMP-2. MMP-2 itself plays an important role in tumor cell invasion and appears to be associated with the development of the characteristic desmoplastic reaction in pancreatic cancer.

Adenocarcinoma↗
PubMed2000

Limitations of magnetic resonance imaging in the evaluation of perineural tumor spread causing facial nerve paralysis.

OBJECTIVE: To present and discuss the clinical presentation and treatment in patients with long-duration unilateral facial paralysis and normal magnetic resonance imaging (MRI) findings. DESIGN: Case series. SETTING: Ear, nose, and throat department of the University of Cologne, Cologne, Germany. PATIENTS: A total of 486 patients with unilateral facial paralysis who were treated from 1986 to 1998. Besides the usual diagnostic workup, a complete electrophysiological evaluation, including investigations such as needle electromyography and neuromyography (also known as electroneurography), of the facial nerve was performed at repeated intervals. In 19 patients, a malignant tumor was delineated with ultrasonography or MRI. In 8 of these patients, the initially performed MRI did not detect any parotid gland lesion causing the paralysis, whereas long duration of the paralysis and electroneurography indicated malignancy. RESULTS: Exploration surgery was performed as total parotidectomy in these 8 patients and malignant parotid gland tumors were proved in all 8 patients. CONCLUSIONS: Individuals with facial nerve paralysis without any signs of regeneration 6 months after the onset of paralysis and/or persistent electrophysiological evidence of ongoing neuronal degeneration should undergo surgical exploration of the parotid gland and facial nerve, even if MRI studies show no tumoral lesion.

Adenocarcinoma↗
PubMed2000

Differential sustained attention/vigilance changes over time in schizophrenics and controls during a degraded stimulus Continuous Performance Test.

The Continuous Performance Test (CPT) is a widely used procedure for sustained attention/vigilance measurement. However, though the key index of vigilance impairment is the decrement of sensitivity over time during the test period, only few studies have examined whether schizophrenics show a larger drop in CPT performance than do healthy controls. 48 schizophrenic inpatients and 48 controls were investigated with the Munich CPT (480 visual stimuli, 25% target stimuli, one stimulus per second). Stimuli were degraded by randomly inverting 40%, 41%, 42%, or 43% of the pixels. Results were calculated separately for three consecutive trial sections. Additionally, PANSS ratings, medication, and other clinical data were documented. Schizophrenics show a vigilance decrement over time, controls show a vigilance increase. Differential vigilance changes were not related to the level of stimulus degradation. Schizophrenics performed worse than controls only at the lowest degradation level. While overall sensitivity correlated negatively with the dose of atypical neuroleptics and benzodiazepines, vigilance shifts over time correlated negatively with the dose of typical neuroleptics. Furthermore, sensitivity was related to the cognitive PANSS syndrome, number of admissions/duration of illness. Differential sensitivity decrements of schizophrenics and controls can be shown if suited CPT procedures are used. The need for basic research on experimental conditions of the CPT as well as examination of the relationship between sustained attention/vigilance decrements and clinical features of schizophrenia is suggested.

Adult↗
PubMed2000

Cone prosthesis for the hip joint.

The shape of the proximal segment of the femur must be taken into account when implanting femoral endoprostheses, especially those intended for cementless anchorage. Numerous femoral prostheses are available for the proximally broadly extending, "trumpet-shaped" morphology. However, the femur often has a narrow, more cylindrical configuration, as is frequently seen with dysplastic hip joints, but variants of the anatomical constitution or ethnic variants are also found. Conventional femoral prostheses with a proximal transverse oval or rectangular cross-section are often incorrectly positioned in those cases because they can fracture the narrow bones. In many instances, even a pathological anteversion attachment cannot be adequately corrected. The cone prosthesis is ideal for this morphology when pre-operative planning indicates good contact between the bone cortex and the middle third of the prosthetic stem. The tapered anchorage of the cone stem in the medullary cavity reamed to a cone shape promotes primary stability, which is a fundamental prerequisite for the osseointegration of a coarse blasted titanium implant. The sharp longitudinal ridges on the prosthetic stem, which tend to cut into the bone, ensure extensive rotational stability, which explains why thigh pain is not associated with the cone prosthesis. The cone prosthesis has proved its worth in 635 implants performed over 9 years, with highly satisfactory clinical and X-ray results. The surgical technique is relatively straightforward, and complications are rare. The patients' subjective satisfaction is particularly remarkable. The success of the operation lies in correct preoperative planning, which ensures that the morphology of the selected femur guarantees contact between the bone cortex and the middle third of the prosthetic stem.

Adolescent↗
PubMed2000

Human herpesvirus type 8 in salivary gland tumors.

BACKGROUND: The new human herpesvirus type 8 (HHV-8) has been detected in all types of Kaposi's sarcomas, as well as in body-cavity lymphomas and Castleman's disease, furthermore molecular biologic studies have identified a number of potential viral oncogenes. There is evidence for sexual transmission of HHV-8 in HIV-seropositive patients, but the route of infection among the HIV-seronegative population is uncertain. Findings of HHV-8 DNA in saliva in some cases are suggestive of nonsexual transmission associated with latent infection of the salivary gland (as it is known for EBV, CMV, HHV-6 and HHV-7). OBJECTIVE: As little is known about the etiological factors of salivary gland tumors and to give more insights into HHV-8 cell tropism normal salivary gland tissue (n=12) and different salivary glands neoplasm (n=58) were tested for HHV-8 sequences and antigens in HIV-seronegative patients. STUDY DESIGN: Biopsies of both normal salivary gland and tumors were investigated for HHV-8 sequences. A nested-PCR method was used for amplification of HHV-8 DNA fragments and the nature of the amplification products was confirmed by Southern blot hybridization. In addition, we used an in situ hybridization technique and immunohistochemical staining for detection of HHV-8 infected cells. The sera of the respective patients were tested for anti-HHV-8 antibodies using commercial IFA and an ELISA-assay. RESULTS: HHV-8 DNA sequences could be detected in one bilateral MALT-lymphoma of the parotid gland of a HHV-8 seropositive female patient suffering from Sjögren's syndrome (SS). The remaining parotid samples did neither show HHV-8 sequences nor HHV-8 antigens. Using above assays only one additional patient was seropositive for HHV-8. CONCLUSION: Our data suggest that HHV-8 does not usually infect the salivary gland in HIV-seronegative patients and does not seem to play a pathogenic role in vascular and epithelial salivary gland neoplasm. Pathogenic role of HHV-8 in Sjögren's syndrome associated MALT-lymphoma remains unclear and should be subject of further studies.

Adult↗
PubMed2000

Characterization of an in vitro model of human melanoma invasion based on reconstructed human skin.

The purpose of this study was to compare the invasive properties of normal human cutaneous melanocytes and of a cutaneous melanoma cell line (HBL) in a three-dimensional model of reconstructed human skin. Specifically, we asked to what extent the pigmentary and invasive behaviour of both cells is influenced by their interaction with adjacent skin cells (keratinocytes and fibroblasts) and the basement membrane (BM). In the presence of a BM, normal human melanocytes within this model remained within the basal layer of keratinocytes and did not pigment spontaneously. When the BM was removed, melanocytes were found suprabasally and pigmented extensively. No significant invasion of melanocytes into the dermis was detected in the presence or absence of the BM. HBL melanoma cells showed no significant ability to invade into the dermis in the absence of other cells, irrespective of the presence or absence of the BM. However, when added to keratinocytes and fibroblasts, HBL cells showed a capacity to invade into the dermis, both in the presence and absence of the BM. Associated with HBL invasion into the dermis, we noted significant keratinocyte entry into the dermis. On their own, keratinocytes entered the dermis in the absence of the BM but showed no significant penetration into the dermis when the BM was present. In summary, this model demonstrates clear differences between melanocytes and a melanoma cell line with respect to their invasive properties. It also allows demonstration of interactions between cells, and between cells and the BM. The study also provides evidence for a synergistic interaction between this melanoma cell line and keratinocytes in penetrating the BM.

Basement Membrane↗
PubMed2000

Ultrastructural changes of human cardiac atrial nerve endings in diabetes mellitus.

BACKGROUND: Autonomic neuropathy resulting from long-term diabetes mellitus may affect heart innervation. However, so far diabetes induced morphological changes of cardiac nerves are not well-known. In this study human cardiac atrial tissue from diabetic patients was analysed by electron microscopy for structural alterations as a result of diabetic neuropathy. METHODS: In coronary bypass surgery, an edge of the right auricle was routinely resected for reason of extracorporal circulation. Thin cardiac tissue sections of 100 nm were studied by electron microscopy. Atrial tissue samples were collected from 5 patients with long-standing diabetes (for at least 8 years) and compared to atrial tissue samples from 5 patients without diabetes, equally undergoing coronary bypass surgery. RESULTS: In all atria-free nerve endings with unmyelinized, axons were observed. Cross sections of 479 axons from diabetic patients were compared to 419 axons of nondiabetic patients. The number of altered axons was significantly higher in cardiac tissue of diabetic patients (32%) in comparison to normal subjects (17%). In diabetic patients, 20% of the intra-axonal mitochondria were condensed or hydropic, whereas in nondiabetic patients only 4% of the mitochondria were altered. Membrane fragments were present in 21% of the axons in atria of diabetic patients compared to 10% in nondiabetic subjects. Only in cardiac axons from diabetic patients there were lamellar bodies, dissolved axoplasma and junctions between neighbouring axons in a minor number. Few vacuoles were present in axons of both groups. CONCLUSION: In myocardial atrial-free nerve fibre bundles of diabetic patients, the amount of degenerative changes was higher in comparison to atrial cardiac tissue from nondiabetic subjects. These morphological alterations may indicate manifestation of diabetic neuropathy and might contribute to the impairment of autonomic neural control affecting the heart in long-standing diabetes mellitus.

Aged↗
PubMed2000

Local treatment of hepatic metastases with low-level direct electric current: experimental results.

BACKGROUND: Several authors have recently reported encouraging results from low-level direct current therapy in easily accessible malignant tumors. However, antitumoral effects in colorectal metastases have not been investigated experimentally. METHODS: Using an animal model with induced hepatic metastases, we analyzed the effectiveness and the tumor growth dynamics after direct current application. Three weeks after induction tumor volumes were estimated with magnetic resonance imaging (MRI). Then direct current (80 C/cm3) was applied in the treatment group by means of one anode in the tumor center and four cathodes peripherally. In the control group electrodes were placed without applying current. Tumor growth dynamics was analyzed with MRI after 3 and 5 weeks. After this all animals were killed, and the livers histologically examined. RESULTS: After 5 weeks MRI showed a 1.6-fold tumor enlargement in the treatment group versus a 2.9-fold enlargement in the control group (Student t test, P=0.0051). The histopathologic analysis of the treated livers yielded a 21% complete response rate and a 78% partial response rate. No necroses were found in the control group. CONCLUSIONS: These results confirm the effectiveness of low-level direct current application as a potential modality for the treatment of hepatic metastases.

Animals↗
PubMed2000

Impact of abdominal CT on the management of patients presenting to the emergency department with acute abdominal pain.

OBJECTIVE: The purpose of this study is to document the impact of CT performed in the emergency department of patients presenting with nontraumatic acute abdominal pain. SUBJECTS AND METHODS: Fifty-seven patients were enrolled in this prospective study. Using a computer order entry system, emergency department physicians were required to report their most likely diagnosis, level of certainty, and management plan for their patients before ordering abdominal CT. After CT was performed, each physician was required to provide again his or her diagnosis, level of diagnostic certainty, and treatment plan. The outcome of each patient was evaluated by either surgery, other imaging studies, or clinical follow-up. RESULTS: After the abdominal CT, physicians' mean level of certainty in their diagnoses increased by 1.5 points (on a five-point scale; p < 0.0001). Patient management was changed in 33 (60.0%) of 55 patients. Planned treatment before CT was admission in 42 patients. Actual admissions after CT totaled 32 patients (excluding the two patients in whom preimaging information was not recorded). Thus, the net effect of abdominal CT scanning was to avert 10 (23.8%) of 42 hospital admissions. CONCLUSION: CT performed in the emergency department increases the physician's level of certainty, reduces hospital admission rates by 23.8%, and leads to more timely surgical intervention.

Abdominal Pain↗
PubMed2000

Single-strand conformation polymorphisms in the hly gene and polymerase chain reaction analysis of a repeat region in the iap gene to identify and type Listeria monocytogenes.

Two novel methods that allow the powerful identification of Listeria monocytogenes by polymerase chain reaction (PCR) and simultaneous differentiation by special electrophoresis formats are described. The first method involves a PCR-driven single-strand conformation polymorphism (SSCP-PCR) assay using a portion of the noncoding region of the hlv gene. The assay was evaluated with 120 genetically distinct L. monocytogenes strains of either foodborne or clinical origin. Distribution of listerial strains to at least 14 SSCP types was observed. In respect to the panel of strains, 39.7% were assigned to SSCP type 3, and 19% showed SSCP type 5. Further, SSCP type 1 was found in 7.5% of all strains, SSCP type 10 in 6.7%, and 5.8% each for SSCP types 6 and 7. The SSCP types 4, 9, and 11 were infrequently described in 2.55%, 3.3%, and 4.2%, respectively, of all isolates. At least 0.85% represented each of the SSCP types 2, 13, and 14, and 1.7% displayed SSCP types 8 and 12. In the second method, the internal threonine-asparagine repeat portion of the L. monocytogenes p60 protein was used for setting up a PCR-based identification and parallel differentiation assay. Ten different repeat types (RTs), according to different sizes of PCR products, were observed. Of 163 strains tested, 35.58% of samples were assigned to RT 1, 39.26% to RT 2, 3.68% to RT 3, 6.13% to RT 4, 4.29% to RT 5, 2.45% to RT 6, 5.52% to RT 7, 0.61% to RT 8, 0.61% to RT 9, and 1.83% to RT 10. The data suggest that both methods allow the simple identification and differentiation of L. monocytogenes isolates. Therefore, both the SSCP-PCR and the PCR-based identification and parallel differentiation assay could represent single-strand pretyping assays before laborious reference typing methods are applied.

Bacterial Proteins↗
PubMed2000

Retinoic acid regulates the morphological development of sympathetic neurons.

Interactions between all-trans-retinoic acid (RA) and bone morphogenetic proteins (BMPs) affect the expression of neurotrophin receptors in sympathetic neurons (Kobayashi et al., 1998). In this study, we examined the possibility that similar interactions might regulate the morphological development of these neurons. Under control conditions, embryonic rat sympathetic neurons formed axons but not dendrites; cells exposed to RA had a similar appearance. Profuse dendritic growth was observed upon exposure to BMP-7, and this was reduced by approximately 70% by RA. This inhibitory effect of RA was mediated primarily by retinoic acid receptors (RARs) and it exhibited substantial specificity because it was not associated with changes in either axonal elongation or cell survival. Moreover, mRNAs for enzymes required for synthesis of RA were expressed in the sympathetic neurons and retinoid activity was released from superior cervical ganglia. These observations suggest that retinoids may function as endogenous morphogens and regulate neural cell shape and polarity in developing sympathetic ganglia.

Alcohol Oxidoreductases↗
PubMed1999

Confocal Scanning Laser Microscopy as a Tool for the Determination of 3D Floc Structure.

Several assumptions are made when confocal scanning laser microscopy is used for the determination of the fractal dimension of aggregates. The purpose of this study is to experimentally show that one of these assumptions, which concerns the relation existing between the structure of an aggregate and that of its sections, is valid. A comparison between the structures of sections and reconstructed 3D edifices of latex aggregates shows that they are both directly related even in the case of relatively small aggregates. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Sum1 and Hst1 repress middle sporulation-specific gene expression during mitosis in Saccharomyces cerevisiae.

Meiotic development in yeast is characterized by the sequential induction of temporally distinct classes of genes. Genes that are induced at the middle stages of the pathway share a promoter element, termed the middle sporulation element (MSE), which interacts with the Ndt80 transcriptional activator. We have found that a subclass of MSEs are strong repressor sites during mitosis. SUM1 and HST1, genes previously associated with transcriptional silencing, are required for MSE-mediated repression. Sum1 binds specifically in vitro to MSEs that function as strong repressor sites in vivo. Repression by Sum1 is gene specific and does not extend to neighboring genes. These results suggest that mechanisms used to silence large regions of chromatin may also be used to regulate the expression of specific genes during development. NDT80 is regulated during mitosis by both the Sum1 and Ume6 repressors. These results suggest that progression through sporulation may be controlled by the regulated competition between the Sum1 repressor and Ndt80 activator at key MSEs.

Binding Sites↗
PubMed1999

Localisation of the cell wall-associated phosphodiesterase PhoD of Bacillus subtilis.

The localisation of phosphate-starvation-induced phosphodiesterase PhoD from Bacillus subtilis was studied by analysing processing, release and immunogold labelling of the sections. Although the processing of the pre-protein was extremely slow, the major fraction of PhoD could be detected at the surface of the cell wall. The results indicate that inefficient processing of the translocated pre-protein keeps PhoD in a cell wall-associated location. The uncleaved signal peptide might function as a membrane anchor.

Antibodies, Bacterial↗
PubMed1999

Development of a multiple primer RAPD assay as a tool for phylogenetic analysis in Listeria spp. strains isolated from milkproduct associated epidemics, sporadic cases of listeriosis and dairy environments.

A total of 82 Listeria strains comprising four species were examined by amplification with a multiple primer random amplified polymorphic DNA (RAPD) assay. It was the objective of the study to set up a procedure suitable for analysis of the relationships among strains from milkproduct-associated epidemics, strains from sporadic cases of listeriosis and field strains from dairy products and dairy environments. In a preliminary study, 205 primers, each 10 bp long, were screened for suitability as primers and 44 primers showing reliable and reproducible RAPD patterns at a defined reaction condition were selected. The 82 strains were assigned to 54 RAPD groups positioned in 13 major clusters. Strains isolated during milk product-associated epidemics were found to belong to a single cluster I. Human isolates from sporadic cases of listeriosis predominantly were assigned to four separate clusters. It was found that strains of clinical origin were mainly assigned to other clusters than strains of non-clinical origin.

Animals↗