Search PubMed⌕ Search

Biomedical subjects

M Schwab

Publications and source records attributed to M Schwab.

At least 109 records · Page 6Linked to original sources
PubMed1998

Secretory type II phospholipase A2 (PLA2G2A) expression status in colorectal carcinoma derived cell lines and in normal colonic mucosa.

There is good evidence now that the secretory type II phospholipase A2 (Pla2g2a) gene represents the Mom1 locus, a genetic modifier of tumor resistance in the multiple intestinal neoplasia (Min) mouse. Previously we have mapped the human homolog PLA2G2A to 1p35-36.1 within a region that is the target of frequent deletions in sporadic colorectal tumors. Here we show 64% loss of heterozygosity (LOH) at the PLA2G2A locus in primary tumors. We studied PLA2G2A expression in both colorectal tumor cell lines and normal mucosa. Most of the lines lacked detectable PLA2G2A transcripts by Northern analysis. Large differences in expression were seen among normal mucosa of different patients with sporadic tumors. We analysed the coding region of PLA2G2A in eight colorectal cancer cell lines with hemizygous deletion at 1p35-36/PLA2G2A, in none we did detect a mutation. Biallelic expression of PLA2G2A was observed in a cell line heterozygous for an exon 3 polymorphism, rendering unlikely that imprinting is a pathway participating in the loss of PLA2G2A function. It remains uncertain if PLA2G2A, in particular its apparent lack of expression in tumor cells, might be a factor in human colorectal tumorigenesis.

Animals↗
PubMed1998

Vestibular caloric responses and behavioral state in the fetal sheep.

Functional activity of the vestibular system in relation to behavioral state of fetal sheep in utero was studied by cooling and heating of the fetal middle ear and skin (control) with implanted copper-tube heat exchangers. Eye movements and fetal cortical activity were assessed before, during, and after 2 min irrigations with water at 6, 46, or 39.5 degrees C (isothermic). Cold water induced slow-phase eye movements toward the irrigated ear followed by saccades toward the opposite ear after a delay of several seconds. The direction of the response reversed with warm water, and saccades were absent during irrigation with body-temperature water. Cold-water irrigations of the skin over the jaw did not result in nystagmus. Arousal-like responses were elicited with thermal stimulation of the ear or facial skin while the fetus was in either rapid eye movement (REM) or non-REM states. Circulation of 39.5 degrees C water through the ear also produced arousal-like responses, possibly due to turbulence-induced noises in the heat exchanger or slight deviations between the irrigation temperature and the actual fetal inner ear temperature. These results suggest that mechanisms responsible for saccade suppression during depressed levels of consciousness (i.e. sleep) are inactive in utero. Fetal behavioral state responsiveness to vestibular and somatosensory thermal stimulation may be of great significance, especially in the premature neonate.

Animals↗
PubMed1998

Isolation and characterization of human SGT and identification of homologues in Saccharomyces cerevisiae and Caenorhabditis elegans.

We have recently isolated a rat cDNA encoding a novel cellular protein able to interact with the major nonstructural protein NS1 of parvovirus H-1 and have termed this protein SGT, for small glutamine-rich tetratricopeptide repeat (TPR)-containing protein. Here we report the isolation of a cDNA from human placenta encoding the human homologue, human SGT. SGT from rat and human contain 314 and 313 amino acids, respectively, and share 91% sequence identity at the protein level. The highest degree of similarity is present within the central region containing three TPR motifs in tandem array. The similarities, however, also extend beyond this region. Human SGTtranscript was found to be ubiquitously present in all human tissues tested. By fluorescence in situ hybridization analysis we have mapped the human gene to chromosome 19p13. The SGT-coding sequences are evolutionarily conserved, since we could identify genes encoding proteins of similar size and structure in the genomes of Saccharomyces cerevisiae and Caenorhabditis elegans.

Amino Acid Sequence↗
PubMed1998

MycN and IFNgamma cooperate in apoptosis of human neuroblastoma cells.

Neuroblastomas undergo spontaneous regression at an unusually high rate. The mechanisms are not clear, but apoptosis may be involved. A large proportion of neuroblastomas is characterized by amplification of MYCN. Using human neuroblastoma cells harbouring tetracycline controlled expression of MYCN we have analysed the role of the MycN protein and IFNgamma in cell death decision. Neither conditional expression of MYCN nor treatment with IFNgamma alone was sufficient to trigger cell death. However, when acting in concert MycN and IFNgamma efficiently triggered cell death, which was accompanied by DNA fragmentation and required caspase activity, two hallmarks of apoptosis. MycN and IFNgamma may cooperate along at least two different pathways. First, IFNgamma increased the CD95 cell surface expression while MycN enhanced the cellular susceptibility for the CD95 mediated death signal. Second, IFNgamma treatment induced expression of BAK mRNA while MycN and IFNgamma in combination increased the amount of Bax protein, another activator of apoptosis, without a concomitant increase in BAX mRNA. MycN also increased cell death in response to TRAIL and TNFalpha, suggesting that enforced MYCN expression in general increases the susceptibility of neuroblastoma cells towards a variety of death stimuli.

Antigens, CD↗
PubMed1998

[Churg-Strauss syndrome with right ventricular tumor].

HISTORY AND CLINICAL FINDINGS: A 47-year-old woman was admitted because of diarrhoea (3-5 stools daily) for 9 days, weakness for 3 weeks and painful wrist swelling, arthralgia and hyperesthesia over the medial aspect of the right thigh for 6 weeks. For 6 years she had been treated for asthma. Two operation had been performed for chronic sinusitis. ADMISSION FINDINGS AND INVESTIGATIONS: There was marked eosinophilia (5889/microliter) and thrombocytopenia (96,000/microliter), markedly increased serological inflammatory parameters and a raised total IgE level (134 IU/ml). The chest radiogram showed pulmonary infiltrates and bone marrow biopsy indicated eosinophilia. Echocardiography revealed a mass, 3 x 8 cm, in the ventral wall of the right ventricle with extension into the outflow tract. DIAGNOSIS, TREATMENT AND COURSE: These findings met the criteria of the American College of Rheumatology for Churg-Strauss syndrome (CSS). On methylprednisolone (1 mg/kg daily) the eosinophil and platelet counts became normal within 5 days and erythrocyte sedimentation rate and the level of C-reactive protein fell. Under cardiopulmonary bypass the tumour was removed, the tricuspid valve replaced, and the right ventricle reconstructed. Histology of the mass revealed it to be an organized thrombus. CONCLUSION: The relationship between the thrombus formation and CSS is unclear. Hypercoagulability connected with the inflammatory process may have played a part in the pathogenesis.

Anti-Inflammatory Agents↗
PubMed1998

Association between the rat homologue of CO-029, a metastasis-associated tetraspanin molecule and consumption coagulopathy.

Recently, we have described a panel of metastasis-associated antigens in the rat, i.e., of molecules expressed on metastasizing, but not on nonmetastasizing tumor lines. One of these molecules, recognized by the monoclonal antibody D6.1 and named accordingly D6. 1A, was found to be abundantly expressed predominantly on mesenchyme-derived cells. The DNA of the antigen has been isolated and cloned. Surprisingly, the gene product proved to interfere strongly with coagulation. The 1.182-kb cDNA codes for a 235-amino acid long molecule with a 74.2% homology in the nucleotide and a 70% homology in the amino acid sequence to CO-029, a human tumor-associated molecule. According to the distribution of hydrophobic and hydrophilic amino acids, D6.1A belongs to the tetraspanin superfamily. Western blotting of D6.1A-positive metastasizing tumor lines revealed that the D6.1A, like many tetraspanin molecules, is linked to further membrane molecules, one of which could be identified as alpha6beta1 integrin. Transfection of a low-metastasizing tumor cell line with D6.1A cDNA resulted in increased metastatic potential and provided a clue as to the functional role of D6.1A. We noted massive bleeding around the metastases and, possibly as a consequence, local infarctions predominantly in the mesenteric region and all signs of a consumption coagulopathy. By application of the D6.1 antibody the coagulopathy was counterregulated, though not prevented. It has been known for many years that tumor growth and progression is frequently accompanied by thrombotic disorders. Our data suggest that the phenomenon could well be associated with the expression of tetraspanin molecules.

Adenocarcinoma↗
PubMed1998

An interstitial tandem duplication of 9p23-24 coexists with a mutation in the BRCA2 gene in the germ line of three brothers with breast cancer.

Germ-line mutations of the BRCA2 gene account for the majority of families with both male and female breast cancer. However, among independently ascertained families with the same mutation, cases of male breast cancer often appear to cluster in a single family or in a particular branch of one family. This suggests that the risk of male breast cancer conferred by BRCA2 mutations may be modified by other genetic or environmental factors. We report a family in which three brothers with breast cancer carry in their germ line two genetic abnormalities: an insertion A at nucleotide 2041 in exon 10 of BRCA2, which leads to premature termination of the encoded protein at codon 615, and a tandem interstitial duplication involving chromosome bands 9p23-24. We propose that the coexistence of this rare chromosomal abnormality with BRCA2 mutation may be augmenting the risk of male breast cancer conferred by the BRCA2 mutation.

BRCA2 Protein↗
PubMed1998

Transfer protein TraM stimulates TraI-catalyzed cleavage of the transfer origin of plasmid R1 in vivo.

Factors contributing directly to the cleavage of the conjugative transfer origin of plasmid R1 in Escherichia coli were investigated. The essential transfer protein TraM was identified as a necessary positive effector of the catalytic activity of TraI relaxase at the R1 transfer origin in the absence of protein TraY. The stimulatory effect of TraM on the cleavage reaction in vivo correlated with the capacity of TraM to bind origin DNA. TraM was shown to be essential for heterologous mobilization of recombinant origin DNA. The requirement for TraM to promote mobilization was distinct from the protein's positive effect on transfer gene regulation. Chimeric traM alleles, fusing heterologous amino and carboxyl coding sequences from the traM genes of the R1 and the IncFI plasmid P307, were used to localize the specificity determinant of TraM's DNA binding activity. Use of the chimeric alleles also revealed that the requirement for TraM in mobilization is origin specific but transfer system independent. No evidence was found for a plasmid specific activity of TraM at a stage in the transfer process subsequent to the initial cleavage of origin DNA. In light of TraM's regulatory functions in transfer gene expression, we propose that TraM could control conjugative DNA processing in response to intracellular levels of transfer proteins.

Bacterial Proteins↗
PubMed1998

Down syndrome, transient myeloproliferative disorder, and infantile liver fibrosis.

BACKGROUND: In neonates, Down syndrome is rarely accompanied by the leukemoid reaction called transient myeloproliferative disorder. PROCEDURES AND RESULTS: We present clinical and histopathologic data of another Down syndrome neonate with transient myeloproliferative disorder and severe infantile liver fibrosis. These findings in our patients are compared in detail with the 20 cases published previously. Similar clinical and laboratory findings were present in all 21. CONCLUSIONS: Knowing the cellular mechanism of hepatic fibrosis and its modulation by growth factors (e.g, platelet-derived growth factor), a pathogenetic link between transient myeloproliferative disorder and the development of liver fibrosis in Down syndrome neonates seems probable. An association of this triad of findings no longer appears to be accidental.

Down Syndrome↗
PubMed1998

Amplification of oncogenes in human cancer cells.

Gene amplification refers to a genomic change that results in an increased dosage of the gene(s) affected. Amplification represents one of the major molecular pathways through which the oncogenic potential of proto-oncogenes is activated during tumorigenesis. The architecture of amplified genomic structures is simple in some tumor types, involving in the vast majority of cases only one gene, such as MYCN in neuroblastomas. On the other hand, it can be complex and discontinuous, involving several syntenic co-amplified genes, such as in the 11q13 amplification in breast cancer, although in many of these cases there may be a single target gene. The presence of different nonsyntenic amplified genes raises the possibility that cells of certain tumors are susceptible to independent amplification events. In general, the amplified genes do not undergo additional damage by mutations. The data indicate that it is the enhanced level of a wild-type protein that contributes to tumorigenesis.

Breast Neoplasms↗
PubMed1998

Brain-derived peptides reduce the size of cerebral infarction and loss of MAP2 immunoreactivity after focal ischemia in rats.

The effects of brain-derived peptides (BDP; Cerebrolysin) upon the amount of brain injury due to focal brain ischemia were assessed. Male Thomae rats were divided randomly into a sham-operated group (n = 5), an ischemic control (untreated) group (n = 7) and an ischemic BDP-treated group (n = 6) and subjected to reversible middle cerebral artery occlusion (MCAO) for 2h followed by 90min of reperfusion. Local cortical blood flow (LCBF) was monitored by Laser-Doppler flowmetry to assess the MCAO and to measure the blood flow in regions peripheral to the infarction. Infarcted areas of the hippocampus and subcortical structures were quantified in hematoxylin and eosin (H&E) stainings. Functional disturbances of the neurons were detected by immunohistochemical staining of the microtubule associated protein MAP2. Moreover, brain edema was estimated morphometrically. LCBF was estimated from the periphery of infarcted areas and was reduced to 55 to 65% of baseline values (p < 0.05). Reperfusion led to LCBF being increased again to baseline values. No differences in LCBF between the control and the BDP-treated animals were found. In the hippocampus, BDP-treated animals showed a significant reduction of loss of MAP2 immunoreactivity in the subiculum and CA1 region by 59% and 64%, respectively, in comparison to control animals (p < 0.05). The amount of irreversibly damaged neurons in these regions was decreased in tendency. However, the inner blade of the dentate gyrus in BDP-treated animals showed a significant reduction of neuronal injury by 98% (p < 0.05). Likewise, BDP treatment reduced the size of the areas showing a loss of MAP2 immunoreactivity in the thalamic and hypothalamic structures by 51% and in the mesencephalon by 81% (p < 0.05). The size of the infarcted areas in these regions (H&E) was reduced in tendency. In the caudate putamen, no protective effect of BDP-treatment could be proven. Cerebral infarction was accompanied by an increase in the volume of the ischemic hemisphere by 10 +/- 1% in the control and 8 +/- 1% in the BDP-treated animals. These findings indicate a beneficial effect for BDP treatment in ameliorating the early effects of focal brain ischemia.

Amino Acids↗
PubMed1998

The German teleradiology system MEDICUS: system description and experiences in a German field test.

MEDICUS is a teleradiology system which has been developed in a joint project of the German Cancer Research Center (Deutsches Krebsforschungszentrum) and the Transfer Center Medical Informatics (Steinbeis-Transferzentrum Medizinische Informatik) in Heidelberg, Germany. The system is designed to work on ISDN lines as well as in a local area network. Special attention has been given to the design of the user interface and data security, integrity, and authentication. The software is in use in 13 radiology departments in university clinics, small hospitals, private practices, and research institutes. More than 25 thousand images have been processed in 6 months. The system is in use in six different application scenarios. MEDICUS is running under the UNIX operating system. The connection of the modalities could in most cases not be realized with the DICOM protocol as older machines were not equipped with this standard protocol. Clinical experiences show that the MEDICUS system provides a very high degree of functionality. The system has an efficient and user friendly graphical user interface. The result of a comparison with other systems shows that MEDICUS is currently the best known teleradiology system. Cost reductions are already obvious, but additional research has to be performed in this field. An even more powerful commercial successor is currently under construction at the Steinbeis-Transferzentrum Medizinische Informatik in Heidelberg.

Ambulatory Care Facilities↗
PubMed1998

Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study.

Several BRCA2 mutations are found to occur in geographically diverse breast and ovarian cancer families. To investigate both mutation origin and mutation-specific phenotypes due to BRCA2, we constructed a haplotype of 10 polymorphic short tandem-repeat (STR) markers flanking the BRCA2 locus, in a set of 111 breast or breast/ovarian cancer families selected for having one of nine recurrent BRCA2 mutations. Six of the individual mutations are estimated to have arisen 400-2,000 years ago. In particular, the 6174delT mutation, found in approximately 1% of individuals of Ashkenazi Jewish ancestry, was estimated to have arisen 29 generations ago (1-LOD support interval 22-38). This is substantially more recent than the estimated age of the BRCA1 185delAG mutation (46 generations), derived from our analogous study of BRCA1 mutations. In general, there was no evidence of multiple origins of identical BRCA2 mutations. Our study data were consistent with the previous report of a higher incidence of ovarian cancer in families with mutations in a 3.3-kb region of exon 11 (the ovarian cancer cluster region [OCCR]) (P=.10); but that higher incidence was not statistically significant. There was significant evidence that age at diagnosis of breast cancer varied by mutation (P<.001), although only 8% of the variance in age at diagnosis could be explained by the specific mutation, and there was no evidence of family-specific effects. When the age at diagnosis of the breast cancer cases was examined by OCCR, cases associated with mutations in the OCCR had a significantly older mean age at diagnosis than was seen in those outside this region (48 years vs. 42 years; P=.0005).

Adult↗
PubMed1998

Hemorrhage after pancreatoduodenectomy.

OBJECTIVE: The authors reviewed the hemorrhagic complications of patients who underwent pancreatoduodenectomies between 1972 and 1996. SUMMARY BACKGROUND DATA: Although recent studies have demonstrated a reduction in the mortality of pancreatic resection, morbidity is still high. Bleeding is a close second to anastomotic dehiscence in the list of dangerous postoperative complications. METHODS: The medical records from a prospective data bank of 559 patients who underwent pancreatic resection at the Surgical Clinic of Mannheim (Heidelberg University) were analyzed in regard to postoperative hemorrhagic complications. Differences were evaluated with the Fisher exact test. RESULTS: The overall mortality rate was 2.7%. Postoperative bleeding occurred in 42 patients (7.5%), with 6 episodes ending fatally (14.3%). Erosive bleeding after pancreatic leak was noted in 11 patients (26.2%), 4 of whom died. Gastrointestinal hemorrhage occurred in 22 patients, and operative field hemorrhage was present in 20 cases. Relaparotomy was necessary in 29 patients. An angiography with interventional embolization for recurrent bleeding was performed in three patients. Seven hemorrhages (4.6%) occurred after pancreatectomy for chronic pancreatitis and 35 episodes of bleeding (8.6%) were encountered after pancreatectomy for malignant disease. Obstructive jaundice was present in 359 patients (63.9%). In this group of patients, 32 (8.9%) postoperative hemorrhages occurred. Preoperative biliary drainage did not influence the type and mortality rate of postoperative hemorrhage in jaundiced patients. CONCLUSION: The prevention of these bleeding complications depends in the first place on meticulous hemostatic technique. Preoperative biliary drainage does not lower postoperative bleeding complications in jaundiced patients. Continuous, close observation of the patient in the postoperative period, so as to detect complications in time, and expeditious hemostasis are paramount.

Adenocarcinoma↗
PubMed1998

A three-generation model for teleradiology.

This paper proceeds from the definition of teleradiology. It identifies three different generations of teleradiology systems and includes those systems that are not regarded as teleradiology systems by the authors. A list of requirements pertinent to users of first-generation teleradiology systems is introduced. Most of the requirements have been realized in a new generation teleradiology system called CHILI.

Computer Simulation↗