PubMed Health⌕ Search

Biomedical subjects

M Schwab

Publications and source records attributed to M Schwab.

At least 217 records · Page 12Linked to original sources
PubMed1990

Amplification of cellular oncogenes: a predictor of clinical outcome in human cancer.

Increased dosage of cellular oncogenes resulting from amplification of DNA is a frequent genetic abnormality of tumor cells and the study of oncogene amplification has been paradigmatic for the usefulness of molecular genetic research in clinical oncology. Certain types of human tumors carry an amplified cellular oncogene at frequencies of up to 50-60%. Human neuroblastoma has been prototypic for the importance of oncogene amplification in tumorigenesis, and evidence is emerging that amplification may be an early event involved in a more malignant form of this cancer. It is unclear at which stage amplification plays a role in other cancers. Amplification of cellular oncogenes is a good predictor of clinical outcome in some human malignancies.

Breast Neoplasms↗
PubMed1990

Cytogenetics and DNA amplification in colorectal cancers.

In vitro cultivated cells of 28 colorectal cancers were analyzed for chromosomal abnormalities that might signal amplification of DNA, either as double minutes (DMs) or homogeneously staining chromosomal regions (HSRs). Cells derived from 18 tumors showed DMs in 10 to 100% of all metaphases examined. Surveys that employed a panel of available oncogene probes failed to detect amplification of a known cellular oncogene with the exception of three cases where the ERBB2 gene was amplified. In one of these three cases neither DMs nor HSRs were detectable. Our studies show that from 28 lines established in culture, 19 (68%) show amplification of DNA, and indicate that DNA amplification is a frequent genetic alteration in colorectal cancers in addition to other genetic changes. Amplification is correlated with high Dukes stage, but not with histological grade. The identity of the amplified DNA remains to be established for most cases.

Animals↗
PubMed1990

An examination of the intra-SMSA distribution of carbon monoxide exposure.

Although fixed-site monitoring data have been used to estimate the spatial pattern of human exposure, the intra-urban distribution of actual exposure has not been documented. This paper used the data collected during the Environmental Protection Agency's (EPA) field investigation of personal exposure to carbon monoxide (CO) to investigate the nature of the distribution of CO with respect to residential location in the Washington, D.C. SMSA. Dot-distribution maps and analysis of variance were used to document the spatial pattern of individual-level in-home CO concentrations. The results show sampled individuals living in the SMSA center are exposed to statistically significantly higher levels of CO than are those living in the suburbs. The most important implications of this work are for exposure modeling. Further investigation is needed to determine whether incorporation of a geographic component will improve exposure prediction.

Carbon Monoxide↗
PubMed1990

Amplification of the MYCN oncogene and deletion of putative tumour suppressor gene in human neuroblastomas.

Human neuroblastoma cells often carry non-random chromosomal abnormalities signalling genetic alterations. Quite frequent are 'double minutes' (DMs) and homogeneously staining regions (HSRs), both cytogenetic manifestations of amplified DNA, and chromosome 1p-deletions indicating loss of genetic information. With the identification of amplified MYCN and the demonstration of a consensus deletion spanning the chromosome 1p36.1-2 region it appears now likely that both amplification of a cellular oncogene and loss of a tumour-suppressor gene play an important role in neuroblastoma. Amplification of MYCN is an indicator for poor prognosis, even when classical morphological criteria would suggest a better outcome. Consequently, patients with amplification are subjected to more intensive therapeutic regimens. Amplification of MYCN is a paradigm for the clinical use of an oncogene alteration.

Child↗
PubMed1990

Oncogene amplification in neoplastic development and progression of human cancers.

Increased dosage of cellular oncogenes resulting from amplification of DNA is a frequent genetic abnormality of tumor cells. Certain types of human tumors carry a specific amplified cellular oncogene at frequencies of up to 50 to 60%. Human neuroblastoma has been prototypic for a contribution of amplification to tumorigenesis, and evidence is emerging that amplification may be an early event involved in a malignant form of this cancer. It is unclear at which stage amplification plays a role in other cancers. Amplification of cellular oncogenes is a good predictor for clinical outcome in some human malignancies and is a paradigm for the application of oncogene research in a clinical context.

Chromosome Aberrations↗
PubMed1989

Suppression of genetic melanoma in the fish Xiphophorus.

Hybrids between certain species of the teleost Xiphophorus predictably develop melanomas. Classical Mendelian crossing experiments have allowed us to identify genetic loci involved in eliciting and in suppressing tumorigenesis. The overall picture is that melanoma formation results from functional elimination of a suppressor locus allowing abnormal expression of a melanoma locus. Melanoma formation in Xiphophorus behaves like a recessive trait. The fish melanomas consist of incompletely differentiated pigment cells and in many aspects resemble their murine and human counterparts. Cytogenetic studies of cells of the genetic melanomas have provided evidence for chromosomal abnormalities. In particular, cytogenetic manifestations of amplified DNA were detected in a cell line derived from a malignant melanoma. Amplified DNA was isolated and was found to be amplified in a particular type of genetic melanoma. Our results suggest that genetic changes in addition to elimination of suppressor genes contribute to the malignant phenotype of melanoma in Xiphophorus. It is possible that a similar situation occurs in cancers of higher vertebrates, including humans.

Animals↗
PubMed1989

Chromosome 1 deletions in human neuroblastomas: generation and fine mapping of microclones from the distal 1p region.

Human neuroblastomas show a high incidence of deletions in the distal region of the short arm of chromosome 1. In pursuit of a molecular analysis of these deletions, we have generated a microclone bank from microdissected 1p35-pter chromosomal fragments. To allow a rapid localization of the microclones, we have also generated a panel of (human x mouse) hybrid cell lines through microcell-mediated chromosome transfer. The hybrid cells contained different portions of the human chromosome 1 on a murine background. A total of 20 randomly chosen single or low-copy microclones were localized by Southern analysis on DNA of the hybrid panel: All probes were derived from chromosome I. Sixteen mapped in region 1p36.1-pter, two in 1p22-p36.1, and another two in 1cen-qter. The mapping of ten of these microclones was further refined by in situ hybridization. Cells of the neuroblastoma line GI-ME-N carry two types of chromosome 1, one cytogenetically normal and another with a translocation reported to be in 1p36.2, i.e., a t(1;?) (p36.2;?) marker. Using cell hybridization, we separated the two chromosome 1 types of GI-ME-N into different hybrid cell clones. Southern hybridization of three microclones from distal Ip to DNA of the hybrid cell clones revealed that the breakpoint in the translocated chromosome I was located in 1p36.1.

Bacteriophage lambda↗
PubMed1989

Neuroblastoma consensus deletion maps to 1p36.1-2.

At least 70% of human neuroblastomas display cytogenetically visible aberrations in the short arm of chromosome 1. We have used a panel of probes detecting polymorphic DNA loci, most of which were derived from a library of microdissected distal 1p chromosome fragments, to compare the hybridization pattern of DNA on nine different tumors and the corresponding normal tissue. In eight of the neuroblastomas allelic loss was observed with at least two probes. The deletions were of different size. Since a consensus deletion in all eight tumors included the segment 1p36.1-2, we conclude that genetic information related to neuroblastoma tumorigenesis is located within this approximately 10 megabase segment. Previous studies have revealed the amplification of MYCN in neuroblastomas. Our study did not provide evidence for a correlation between MYCN amplification and the 1p deletion, suggesting that the two genetic alterations result from molecular mechanisms that are not directly related to each other.

Alleles↗
PubMed1989

Suppression of MYC by high expression of NMYC in human neuroblastoma cells.

Members of the MYC gene family, including MYC, NMYC, and LYMC, have been found amplified and expressed at high level in various human cancers. We have analysed the expression of two members of the MYC gene family, NMYC and MYC, in human and murine neuroblastoma cells. Whenever NMYC and MYC are co-expressed, MYC expression predominates. Cells carrying high expression of NMYC as result of amplification lack MYC expression. The same is ture for neuroblastoma cells in which expression of a single-copy NMYC is upregulated or into which a vector forcing high expression of an exogenous NMYC had been introduced by transfection. Our studies indicate a regulatory interaction between MYC and NMYC in neuroblastoma cells.

Cloning, Molecular↗
PubMed1989

Amplified N-myc in human neuroblastoma cells is often arranged as clustered tandem repeats of differently recombined DNA.

Human neuroblastoma cells often carry amplified DNA encompassing the gene N-myc. Amplified N-myc has been found localized in "double minutes" in direct tumor cell preparations. In contrast, later passages carried amplified N-myc almost exclusively within a single homogeneously staining chromosomal region located at a chromosomal site different from the normal location of N-myc. We used pulsed field gel electrophoresis to define the structural arrangement of the amplified DNA. Long-range mapping was facilitated by the presence of several sites for rare cutting restriction endonucleases in the 5' region of N-myc. Amplified DNAs of different neuroblastoma cell lines were heterogeneous in size and had undergone recombination at various distances from N-myc. N-myc occupied a central position within the amplified DNA, and in no case was the coding region affected by recombination. Among neuroblastoma cells, varying proportions of amplified DNA (in some instances close to 100%) consisted of multiple tandem arrays of DNA segments ranging in size from 100 to 700 kilobase pairs. Tumor cells with low degrees of amplification revealed regions of amplified DNA in excess of 1,500 kilobase pairs without apparent rearrangement. Our observations, in concert with the cytogenetic findings, suggest a model of gene amplification which involves unscheduled DNA replication, recombination, and formation of extrachromosomal DNA followed by integration into a chromosome and subsequent in situ multiplication. The central position which N-myc occupies within the amplified sequences and the lack of recombination within the coding region of N-mc indicate that N-myc rather than other genetic information provides the selective advantage for retention of the amplified DNA.

DNA Replication↗
PubMed1989

Genetic suppression of malignancy.

Genetic tumours of Xiphophorus are one of the classical experimental models that underline the concept that cancers develop as a result of abnormal gene expression. Formal genetics has indicated that cancer development in Xiphophorus starts when oncogenes are expressed abnormally due to elimination of tumour suppressor genes. The suppressor gene Diff seems to suppress malignancy by controlling terminal differentiation of cells. It appears now that control of terminal differentiation may also be one of the properties of human tumour suppressor loci, in particular the Rb gene. Although it is difficult at this point to envision which molecular or biochemical function of tumour suppressor genes we might be able to identify, research on tumour suppression will at least allow another glimpse at how basic mechanisms of cell differentiation and multiplication operate. It is not clear, however, if elimination of tumour suppressor genes alone is sufficient to elicit the fully malignant phenotype. Cytogenetic studies have shown various nonrandom chromosomal abnormalities in those human tumours in which elimination of a tumour suppressor gene seems to be a critical step in tumorigenesis. In Xiphophorus, it is obvious from our molecular studies that additional genetic events can contribute to the malignant phenotype. Of these, amplification of cellular DNA may have a role in malignant progression of melanomas. At this point, the exact contribution of amplification to genetic melanoma is unclear. Judging from the role of amplification in human and murine tumours, the significance of amplification, in addition to suppressor elimination, in melanomas of Xiphophorus is likely to be high.

Animals↗
PubMed1989

[Assessment of kidney function before cisplatin administration: the need for 24-hour urine collection].

Creatinine clearance as a measure of the glomerular filtration rate is calculated from the serum creatinine, urine creatinine concentration and the 24-h urine volume (MCC). Cockroft and Gault as well as Davila and Gardener have shown that estimation of the creatinine clearance (ECC) from the serum creatinine, age, sex, and weight of the patient is at least as accurate as measurement of creatinine clearance (MCC). ECC is not influenced by inaccurate collections of urine or incorrect analyses of urine creatinine. 125 MCC was investigated in 51 patients receiving cisplatin. If ECC is less than or equal to 80, then MCC should eliminate inaccurate urine collections. If the value of ECC exceeds 80, it is not necessary to measure MCC.

Circadian Rhythm↗
PubMed1989

[Infarct ECG following a lightning accident].

A 17-year-old man was resuscitated after being struck by lightning. The ECG showed a development similar to anterior infarction. The patient died on the 12th day due to irreversible brain damage. Autopsy showed normal myocardium.

Adolescent↗
PubMed1989

Amplified DNA in cells of genetic melanoma of Xiphophorus.

Melanomas of genetic origin develop in interspecies hybrids of the fish Xiphophorus. Cytogenetic analyses have indicated chromosomal manifestations of amplified DNA in cells of an in vitro established cell line derived from a melanoma. We have employed strategies of differential hybridization in agarose gels to isolate and clone a portion of the amplified DNA. Amplification was about 20-fold in melanoma cells established in culture and about 10-fold in 2 out of 5 melanomas directly derived from the animal. The amplified DNA contained at least one transcription unit that is evolutionarily conserved in all vertebrates tested, including chicken, murines and man. Our results indicate that amplification of an as yet uncharacterized gene is involved in genetic melanoma of Xiphophorus.

Animals↗
PubMed1988

Evidence for neurotransmitter plasticity in vivo. II. Immunocytochemical studies of rat sweat gland innervation during development.

Previous studies of the cholinergic sympathetic innervation of rat sweat glands provide evidence for a change in neurotransmitter phenotype from noradrenergic to cholinergic during development. To define further the developmental history of cholinergic sympathetic neurons, we have used immunocytochemical techniques to examine developing and mature sweat gland innervation for the presence of the catecholamine synthetic enzymes tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) and for two neuropeptides present in the mature cholinergic innervation, vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP). In 7-day old animals, intensely TH- and DBH-immunoreactive axons were closely associated with the forming glands. The intensity of both the TH and DBH immunofluorescence decreased as the glands and their innervation developed. Neither TH-IR nor DBH-IR disappeared entirely; faint immunoreactivity for both enzymes was reproducibly detected in mature animals. In contrast to noradrenergic properties, the expression of peptide immunoreactivities appeared relatively late. No VIP-IR or CGRP-IR was detectable in the sweat gland innervation at 4 or 7 days. In some glands VIP-IR first appeared in axons at 10 days, and was evident in all glands by 14 days. CGRP-IR was detectable only after 14 days. In addition to VIP-IR and CGRP-IR, we examined the sweat gland innervation for several neuropeptides which have been described in noradrenergic sympathetic neurons including neuropeptide Y, somatostatin, substance P, and leu- and met-enkephalin; these peptides were not evident in either developing or mature sweat gland axons. Our observations provide further evidence for the early expression and subsequent modulation of noradrenergic properties in a population of cholinergic sympathetic neurons in vivo. In addition, the asynchronous appearance during development of the two neuropeptide immunoreactivities raises the possibility that the expression of peptide phenotypes may be controlled independently.

Animals↗