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M Schwab

Publications and source records attributed to M Schwab.

At least 163 records · Page 9Linked to original sources
PubMed1996

[Is diagnostic laparoscopy a reliable addition to preoperative staging of pancreatic carcinoma?].

Over the last decade several authors proposed adopting diagnostic laparoscopy as an early diagnostic routine method in the staging of pancreatic carcinoma to prevent exploratory laparotomy. In our hospital only 11.6% of all patients who underwent explorative laparotomy would have benefitted from diagnostic laparoscopy. Therefore, we do not recommend diagnostic laparoscopy as a routine method to assess resectability of pancreatic carcinoma?

Angiography↗
PubMed1996

[Extensive palliative carcinoma operation--is it really worthwhile? What are the aims?].

This question can be approached from 3 viewpoints. 1. Economics. Here it becomes clear that calculations of cost-effectiveness-important as they are-are meaningless for any individual case. 2. Internal quality control found 138 patients (out of a total of 1200 oncological procedures performed in 1993/94) who had extensive palliative cancer operations. With an overall operative mortality of 9.4%, 59 were still alive after a mean follow-up period of 15 months; among the 49 who could be reached 60% rated their quality of life to be "satisfactory" to "very good". However, in the end, quality control figures are of little help for the individual case. 3. Selected individual case histories concerning surgery for metastases make it abundantly clear that the answer to the title's question must be found a new by each individual patient and his surgeon.

Cost-Benefit Analysis↗
PubMed1995

Human homologue of a candidate for the Mom1 locus, the secretory type II phospholipase A2 (PLA2S-II), maps to 1p35-36.1/D1S199.

Mice heterozygous for the dominant Min mutation in their Apc gene develop multiple intestinal neoplasia. Analogously, family members from familial adenomatous polyposis kindreds inheriting mutations in their human APC homologue develop a similar phenotype. Quantitative trait loci studies have identified the Mom1 locus (for modifier of Min-1), which is responsible for part of the genetic variability in polyp number found among inbred mouse strains. The secretory type II phospholipase [nonpancreatic Pla2s (type II Pla2s or Pla2s-II)] has been demonstrated to be a candidate for Mom1, and a mutation in Pla2s-II in mice carrying the Min mutation has been proposed to account for an increased polyp number compared to mice without the Pla2s-II mutation. In this study, we have mapped the chromosomal position of the human homologue of Pla2s-II. We have identified 3 mega-yeast artificial chromosomes that carry PLA2S-II and localized one of them by fluorescence in situ hybridization to the border between 1p35 and 1p36.1. The presence of the microsatellite marker D1S199 in all three clones integrates PLA2S-II into different genetic maps. This highly polymorphic CA repeat D1S199 has previously been shown by us to identify loss of heterozygosity in 48% of sporadic colorectal tumors, indicating that the human homologue of the Pla2s-II/Mom1 locus might be related to human colorectal cancer.

Base Sequence↗
PubMed1995

The 1p deletion is not a reliable marker for the prognosis of patients with neuroblastoma.

Human neuroblastoma cells often have deletions of the distal short arm of chromosome 1 (1p). Earlier studies using chromosome analysis had suggested that the 1p deletion is correlated with a poor survival chance for the patient. We have reevaluated this possibility by analyzing 51 neuroblastomas for loss of heterozygosity (LOH) at 1p. We detected LOH in 32% of the cases. LOH did not correlate with the age of the patients at diagnosis or with tumor stage but was correlated significantly with amplification of the MYCN proto-oncogene. Nine of 10 MYCN-amplified tumors had deletions in 1p (P < 0.001). Survival chances of patients with tumors carrying MYCN amplification together with the deletion at 1p were decreased significantly (eight of nine affected patients died) compared with a patient group without any of these aberrations (P < 0.001). However, the deletion of 1p alone without MYCN amplification was not associated with a poor outcome compared with patients who had neither deletion nor amplification (only two of eight affected patients died; P = 0.803). From these data we conclude that 1p deletions are not reliable markers to determine a patient's prognosis. They may, however, identify a subgroup of neuroblastomas in which MYCN is amplified readily, resulting in rapid tumor progression.

Adult↗
PubMed1995

Experimental Listeria meningoencephalitis. Macrophage inflammatory protein-1 alpha and -2 are produced intrathecally and mediate chemotactic activity in cerebrospinal fluid of infected mice.

In bacterial meningitis, the recruitment of leukocytes across the blood-brain barrier into the central nervous system may be crucial for both elimination of pathogens and tissue injury. In addition to bacterial cell wall products, host factors including chemokines may lead to accumulation of phagocytes within the central nervous system. As shown by Northern analysis, brains of mice infected intracerebrally with Listeria monocytogenes (LM) express mRNA for three chemokines, the macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and MIP-2. The cellular sources of these chemokines comprise both the blood-derived polymorphonuclear leukocytes (PMNs) and monocytes infiltrating the meninges, the ventricular system and the periventricular area. In the course of meningitis a time-dependent increase of MIP-1 alpha and MIP-2 was found in the cerebrospinal fluid (CSF) by ELISA. CSF taken 24 h after infection (CSF-LM24) induced migration of human leukocytes when treated in chemotactic chambers in vitro. Neutralizing Abs to chemokines identified MIP-1 alpha and MIP-2 to be responsible for CSF-LM24 mediated chemotaxis of monocytes and PMNs, respectively. CSF obtained from mock-infected animals contained no MIP-1 alpha or MIP-2 and did not lead to migration of leukocytes. When testing CSF-LM24 on mouse spleen cells, the chemotactic activity detected for mononuclear cells was only partly inhibited by Abs to MIP-1 alpha and -1 beta. Thus, in addition to MIP-1 and -2 other not yet defined chemotactic factors are of importance for recruitment of leukocytes in bacterial meningitis.

Animals↗
PubMed1995

Deletion mapping defines different regions in 1p34.2-pter that may harbor genetic information related to human colorectal cancer.

Cytogenetic and molecular analyses of colorectal cancer cells have revealed deletions at 1p as prominent alterations, suggesting that genetic information on the short arm of chromosome 1 has a role in tumorigenesis. In this study we have used 33 microsatellite markers to fine map deletions at 1p in primary colorectal carcinomas. We found 1p-deletions in 84% of the cases (31/37). High frequencies of loss of heterozygosity (LOH), often the result of small independent interstitial deletions in the same tumor, defined three regions, that may harbor genetic information relevant for colorectal cancer: (i) region A between D1S243 and D1S468 (7cM; 1p36.3); (ii) region B between D1S436 and D1S199 (7cM; 1p35.1-36.31) and (iii) region C between D1S496 and D1S255 (1cM; 1p34.2-35). In addition we identified seven cell lines with LOH at 1p, all of which have deletions that span at least from the distal border of region A to the proximal border of region C.

Chromosome Deletion↗
PubMed1995

Duplication of N-MYC at its resident site 2p24 may be a mechanism of activation alternative to amplification in human neuroblastoma cells.

Amplification of the human N-MYC proto-oncogene is frequently seen either in extrachromosomal double minutes or in homogeneously staining regions of aggressively growing neuroblastomas. N-MYC maps to chromosome 2 band p23-24, but homogeneously staining regions have never been observed at this band, suggesting transposition of N-MYC during amplification. Previous studies had suggested that in cells with amplified N-MYC the chromosomes 2 appear to be unaltered and to carry one apparently normal copy of N-MYC each. In contrast, the contribution of N-MYC to tumors which lack amplification has been unclear. We here show, by fluorescence in situ hybridization, that N-MYC is occasionally duplicated at its resident site in neuroblastoma cell lines previously thought to have a single copy gene. Additionally, we detected duplication in a neuroblastoma cell line carrying amplification. Our results raise the possibility that duplication may, in some neuroblastomas, either be a prelude to amplification or an alternative pathway by which N-MYC becomes activated.

Chromosomes, Human, Pair 2↗
PubMed1995

Non-syntenic amplification of MDM2 and MYCN in human neuroblastoma.

Amplification of the MYCN gene is a well documented genetic alteration of aggressively growing human neuroblastomas. Through cytogenetic studies we have identified neuroblastoma cell lines which, in addition to amplified MYCN, carry amplified DNA not harbouring MYCN. In situ hybridization of biotinylated total genomic DNA to metaphase chromosomes of normal human lymphocytes by reverse genomic hybridization revealed the amplified DNA to be derived from chromosome 12 band q13-14. Subsequent filter analyses showed a 20- to 40-fold amplification of the MDM2 gene, located at 12q13-14, both in three cell lines and in an original tumor, in addition to amplified MYCN. As the apparent consequence of amplification abundant MDM2 protein was present, a part of which was complexed with p53.

Chromosomes, Human, Pair 12↗
PubMed1995

A reciprocal translocation (1;15) (36.2;q24) in a neuroblastoma cell line is accompanied by DNA duplication and may signal the site of a putative tumor suppressor-gene.

Cytogenetic analyses and molecular deletion studies of human neuroblastomas have indicated the chromosomal bands 1p36.1-1p36.2 as a location of genetic information which may be involved in tumorigenesis. To define this putative neuroblastoma locus in more detail we have analysed cell lines with alterations of distal 1p. Here we show, by fluorescence in situ hybridization (FISH), that cell line NGP has a reciprocal 1;15 translocation. Loci D1S214/D1S96 could be shown to map telomeric/distal, D1S228 centromeric/proximal to the break. We have identified yeast artificial chromosomes (YACs) that cover the break and map to D1S160 and D1S244. This chromosomal position is within the smallest region of overlap (SRO) found in neuroblastoma tumors (Weith et al., 1989; Caron et al., 1993; Schleiermacher et al., 1994) and within the region of a constitutional interstitial deletion of a neuroblastoma patient (Biegel et al., 1993). Mapping studies with FISH revealed that the translocation is associated with duplication of DNA. It appears, as if the subchromosomal region we describe here is a good candidate for harboring the postulated neuroblastoma suppressor-gene.

Base Sequence↗
PubMed1995

Cytogenetic evolution of MYCN and MDM2 amplification in the neuroblastoma LS tumour and its cell line.

Amplification of the MYCN gene is frequently seen either in extrachromosomal double minutes (DMs) or in homogeneously staining regions (HSRs) of aggressively growing neuroblastomas. Total genomic DNA from cell line LS, from early passages of the same line and from original tumour material was biotinylated and hybridised to metaphase chromosomes of normal human lymphocytes. The reverse genomic hybridisation revealed the amplified DNA to be derived both from chromosome 2p23-24, which is the position of MYCN, and from chromosome 12 band q13-14. The MDM2 gene, located at 12q13-14, was found amplified both in early and late passages of LS, in addition to amplified MYCN. Amplification units of MYCN and MDM2 appear first to develop within DMs, which then integrate into different chromosomes to develop to HSRs.

Chromosomes, Human, Pair 12↗
PubMed1995

The mycN/max protein complex in neuroblastoma. Short review.

The oncogenic activation by amplification of the MYCN gene is frequently observed in human neuroblastomas and occasionally in other tumours with neuronal qualities. As a consequence of amplification, elevated levels of the mycN protein are expressed. mycN contains a C-terminal basic region (BR) that can bind to DNA, and a helix-loop-helix (HLH)-leucine zipper (Zip) domain, which is responsible for the physical interaction with another HLH-Zip protein, max. This principle structure is conserved among all members of the MYC gene family. The resulting dimers can bind to the DNA sequence CACGTG. The mycN protein, but not max, contains, near the N-terminus, a region conferring the ability to activate the transcription of genes. mycN/max heterodimers probably activate and max/max homodimers repress transcription of, as yet, unidentified target genes. In neuroblastoma cells, where mycN is deregulated, the balanced interaction of BR-HLH-Zip proteins is probably perturbed, and, therefore, genes controlled by mycN might be abnormally expressed and thereby alter normal cell growth with the consequence of tumorigenesis.

Base Sequence↗
PubMed1995

Reciprocal translocation at 1p36.2/D1S160 in a neuroblastoma cell line: isolation of a YAC clone at the break.

Band 1p36.1-1p36.2 is frequently involved in chromosomal aberrations of neuroblastoma cells, and therefore thought to harbour genetic information which may be involved in tumorigenesis. To map this putative neuroblastoma locus, we screened neuroblastoma cell lines for reciprocal translocations at 1p36.1-2 which may signal the site of an affected gene. We identified a reciprocal 1;15 translocation in cell line NGP by fluorescence in situ hybridisation (FISH). As a strategy to clone the translocation breakpoint, we isolated yeast artificial chromosomes (YACs) specific for loci at 1p36. Screening of cell line NGP by FISH identified a YAC, 1050 kbp in size, which hybridised to both derivative 1;15 and 15;1 chromosomes. We conclude that this YAC, which maps to D1S160, covers the break. This chromosomal position is within the smallest region of overlap (SRO) found in neuroblastoma tumours and within the region of a constitutional interstitial deletion of a neuroblastoma patient. The YAC we describe here should serve as a DNA source for gene cloning approaches towards the isolation of candidates for the putative neuroblastoma suppressor gene.

Chromosomes, Artificial, Yeast↗
PubMed1995

[Diagnostic and therapeutic problems of acute lower gastrointestinal hemorrhage].

In a four year period (1990-93) 75 patients were treated in our hospital for acute lower gastrointestinal bleeding. In the course of diagnostic procedures an upper gastrointestinal bleeding was excluded routinely and further 126 endoscopic measures were performed. All patients underwent rectoscopy and additional partial or total coloscopy. In addition to that, 16 scintigrams and 7 angiograms were taken. The validity of the endoscopic measures was 0.73, scintigraphy and angiography were less valid with 0.53 and 0.34. Therefore endoscopic diagnostic procedures are of more value. 32 of these 75 patients underwent operative treatment. Recurrent bleeding after operative treatment was seen in 6.25%. Overall mortality was 5.33%. Because prognosis of a recurrent bleeding after operative treatment is poor, primary subtotal colectomy is indicated when the source of bleeding can not be localized.

Aged↗
PubMed1994

MYCN is retained in single copy at chromosome 2 band p23-24 during amplification in human neuroblastoma cells.

Amplification of the human N-myc protooncogene, MYCN, is frequently seen either in extrachromosomal double minutes or in homogeneously staining regions of aggressively growing neuroblastomas. MYCN maps to chromosome 2 band p23-24, but homogeneously staining regions have never been observed at this band, suggesting transposition of MYCN during amplification. We have employed fluorescence in situ hybridization to determine the status of MYCN at 2p23-24 in five human neuroblastoma cell lines. All five lines carried, in addition to amplified MYCN in homogeneously staining regions or double minutes, single-copy MYCN at the normal position. In one line there was coamplification of MYCN together with DNA of the host chromosome 12, to which MYCN had been transposed. Our results suggest a model of amplification where MYCN is retained at its original location. They further sustain the view that either the initial events of MYCN amplification or the further evolution of amplified MYCN copies follow mechanisms different from those leading to amplification of drug-resistance genes.

Chromosomes, Human, Pair 12↗
PubMed1994

There may be two tumor suppressor genes on chromosome arm 1p closely associated with biologically distinct subtypes of neuroblastoma.

We studied loss of heterozygosity (LOH) on chromosome arm 1p in 108 neuroblastomas using 14 polymorphic DNA markers. One-hundred and four tumors with one or more informative loci; 21 (20%) of the 104 tumors showed LOH on 1p, and were classified into three groups on the basis of interstitial or terminal allelic loss, and presence or absence of LOH on 1p. Seven of the 21 tumors showed an interstitial deletion which encompassed a small region in 1p36 (group A), and the other 14 showed a terminal deletion which encompassed the region from 1pter to 1p32 (group B). Eighty-three tumors without LOH on 1p were classified as group C. The group A patients were mostly less than 12 months of age (6/7), were frequently found by a mass screening program for infants (5/7), had a tumor of non-adrenal origin, and rarely progressed to stage IV (1/7). Most group B patients were 12 months or older (11/14), were found clinically (11/14), had tumors of adrenal origin, and progressed to stage IV (10/14). Analysis of biologic characteristics in group C tumors suggested that they may comprise group A and B tumors. While all group A tumors were in the triploid range (3n) (4/4), most group B tumors were diploid (2n) or tetraploid (4n) (7/10). MYCN amplification was found in 8 group B tumors, but in none of group A tumors. Event-free survivals of groups A, B, and C patients at 3 years were 86, 49, and 74%, respectively (P = 0.0287). These findings suggest that there may be two tumor suppressor genes on 1p which are closely associated with two biologically distinct subtypes of neuroblastoma.

Alleles↗