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I Petersen

Publications and source records attributed to I Petersen.

At least 73 records · Page 4Linked to original sources
PubMed1996

Admission levels of serum Gc-globulin: predictive value in fulminant hepatic failure.

Gc-globulin scavenges actin released from necrotic hepatocytes to the extracellular space. In 77 patients with fulminant hepatic failure (FHF) (excluding patients treated with liver transplantation), admission levels of serum Gc-globulin and degree of complexing with monomeric actin (complex ratio) were determined to evaluate their predictive values in relation to survival/nonsurvival. Gc-globulin levels were significantly reduced in 47 nonsurvivors, compared with 30 survivors (96 +/- 71 mg/L vs. 169 +/- 101 mg/L, P < .001), whereas the complex ratio in nonsurvivors did not differ significantly from that of survivors. Gc-globulin levels were significantly lower in 59 patients with non-acetaminophen-induced FHF, compared with 18 patients with acetaminophen-induced FHF (P < .01). Using a cutoff level of serum Gc-globulin of 100 mg/L, a lesser value correctly predicted nonsurvival in 79 percent of patients with non-acetaminophen-induced FHF, whereas a higher value predicted survival in 60 percent. In patients with acetaminophen-induced FHF, nonsurvival was correctly predicted in 100 percent of patients and survival in 53 percent. In comparison, the King's College Hospital (KCH) criteria correctly predicted nonsurvival and survival in 69 percent and 57 percent, respectively, of the same non-acetaminophen-induced FHF patients and in 60 percent and 38 percent, respectively, of the acetaminophen-induced FHF patients. Thus, in our study population, the predictive properties of Gc-globulin were in the same range as the KCH criteria. An advantage of Gc-globulin is that it gives an estimate of the outcome already on admission. Acute liver transplantation should be considered in FHF patients with Gc-globulin less than 100 mg/L.

Acetaminophen↗
PubMed1996

[Comparative genomic hybridization. A screening method in genetic tumor diagnosis].

Comparative genomic hybridization (CGH) is a new method of screening a tumor for genetic changes. The alterations are classified as DNA gains and losses and reveal a characteristic pattern that includes mutations at the chromosomal and subchromosomal levels. Although DNA from fresh-frozen tissue is recommended as the starting material, archival specimens can also be analyzed. Various examples are presented that illustrate the changes that occur in different tumor entities, and preneoplastic lesions, the differentiation of primary tumors from metastases, and the investigation of tumor cell lines that are resistant to cytostatic drugs. These examples emphasize that CGH can extend the possibilities for genetic diagnosis in tumor pathology.

Cell Line↗
PubMed1996

[Analysis program for quantitative detection of chromosome aberrations using comparative genomic hybridization].

Comparative genomic hybridization (CGH) is a molecular cytogenetic method for the detection of chromosomal imbalances between a tumor and a normal genome. In order to produce quantitative and reproducible results, we developed an image analysis program that allows the detection and mapping of the genetic alterations. The result is represented as a CGH sum karyogram in which the genetic changes are documented as color coded-chromosomes. The aim of our investigation is to correlate the genotype with the phenotype on the basis of CGH sum karyograms and thus to achieve a genetic characterization that will supplement the morphological tumor description.

Cell Transformation, Neoplastic↗
PubMed1996

[Allele losses in squamous cell carcinomas of the larynx].

BACKGROUND: Loss of function of tumor suppressor genes is important in the origin and progression of malignant tumors. Analysis for loss of heterozygosity (LOH) in tumors has been used to detect chromosomal regions that could harbor these genes. METHODS: We investigated 30 paired samples of tumor and normal DNA of 20 patients with laryngeal squamous cell carcinoma. Using polymerase chain reaction (PCR), we studied microsatellite polymorphisms on 3 p, 5q, 9 p, 9q, and 17 p. We separated PCR products by denaturating gel electrophoresis and then visualized them colorimetrically. RESULTS: Allelic loss was observed most frequently on 3 p (45%), followed by 9 p (15%), 17 p (6%), and 5 q (5%), while chromosome 9 q displayed no LOH. When primary tumor and lymph node metastases were investigated, the same genetic pattern was observed. No correlation was found between LOH and tumor stage. The commonly deleted region of 3 p was at the chromosomal bands 3 p24-3 p25. Our data demonstrate that chromosome 3 p allelic loss is a common event in head and neck cancers and suggest that tumor suppressor genes on chromosome 3 p contribute to the pathogenesis of these tumors. CONCLUSIONS: A longer follow-up will reveal if the assessment of LOH can be associated with prognostic significance in laryngeal carcinomas.

Aged↗
PubMed1996

[Genetic screening of head-neck carcinomas using comparative genomic hybridization (CGH)].

BACKGROUND: Comparative Genomic Hybridization (CGH) is a novel cytogenetic method that allows the comprehensive analysis of a tumor genome for DNA gains and losses. METHODS: CGH was performed on genomic DNA extracted from 14 primary head and neck squamous cell carcinomas. Equal amounts of biotin-labeled tumor DNA and digoxigenin-labeled normal reference DNA were hybridized to normal metaphase chromosomes. The tumor DNA was visualized with fluorescein (FITC) and the normal DNA with rhodamine (TRITC) and detected in a fluorescence microscope. The signal intensities of the different fluorochromes were quantitated as gray levels along the single chromosomes. The over-and underrepresented DNA segments were quantified by computation of FITC/TRITC ratio images and average ratio profiles. RESULTS: Consensus deletion regions were most frequently observed on chromosome arms 3p (14 cases), 9p (11), 13q (10), 18q (10), 5q (9), 4q (9), 4p (7), 11q (7), 6q (6), 8p (6), and 11p (6). Copy number increases were identified for chromosomes 3q (11), 16p (9), 17q (9), 19p (8), 19q (7), 22 (7), 1p (6), 8q (6), 9q (6), and 20q (6). Particularly, the 3q isochromosome formation (3p loss/3q amplification), found in 10 cases, was a basic alteration. In addition, 11 tumors showed a 11 q13 amplification. CONCLUSION: CGH analysis allows the identification of recurrent genetic alterations in head and neck squamous cell carcinomas that will be associated with specific tumor phenotypes like metastatic behavior and prognosis.

Adult↗
PubMed1996

Use of non-radioactive detection in SSCP, direct DNA sequencing and LOH analysis.

Aims-To develop a protocol that is applicable to single strand conformation polymorphism (SSCP), direct sequencing and loss of heterozygosity analysis of DNA.Methods-The protocol is based on the detection of biotinylated DNA by a Streptavidin-alkaline phosphatase conjugate. Biotinylation of DNA was achieved by using 5'-end biotinylated primers for PCR. After polyacrylamide gel electrophoresis, the DNA fragments were transferred to a nylon membrane by contact blotting. Depending on the alkaline phosphatase substrate, DNA was visualised either colorimetrically or by chemiluminescence.Results-The method was verified by the identification and characterisation of p53 mutations by SSCP analysis and direct DNA sequencing, as well as the assessment of DNA loss in human lung carcinomas by microsatellite polymorphism allelotyping.Conclusions-The protocol is simple, does not require specialised equipment and would be particularly useful for laboratories with experience in Streptavidin-biotin methodology.

Journal Article↗
PubMed1994

Mapping of multiple DNA gains and losses in primary small cell lung carcinomas by comparative genomic hybridization.

Comparative genomic hybridization was applied for a comprehensive screening of under- and overrepresentation of genetic material in 13 autoptic small cell lung cancer specimens. The most abundant genetic changes include DNA losses of chromosome arms 3p, 5q, 10q, 13q, and 17p and DNA gains of 3q, 5p, 8q, and 17q. Amplification sites in these tumors were mapped to 22 chromosome bands. The most frequently involved band was 19q13.1 (4 cases). Bands 1p32, 2p23, 7q11.2, 8q24, and 13q33-34 were involved in two cases each.

Autopsy↗
PubMed1994

p53 mutations in primary human lung tumors and their metastases.

In a total of 26 primary human lung tumors and 60 metastases derived from them, exons 5-8 of the p53 tumor suppressor gene were analyzed by single-strand conformation polymorphism and subsequent direct DNA sequencing of amplified DNA. Mutational inactivation of the p53 gene was identified in four of five squamous cell carcinomas, three of nine adenocarcinomas, and two of nine small-cell carcinomas, the overall incidence being 35%. Point mutations occurred at a similar incidence in exons 5-8, with a preference for G-->T transversions. In seven of nine cases (78%), mutations were identical in the primary tumor and all of its metastases, indicating that in lung tumors, p53 mutations usually precede metastasis and that hematogenic and lymphogenic dissemination of tumor cells to other tissues is not associated with a selection against p53 inactivation. In one case, a kidney metastasis had the same mutation as the primary squamous cell carcinoma, whereas a liver metastasis had no mutation, indicating heterogeneity of the primary lung neoplasm and selective metastasis of mutated and nonmutated tumor cells to kidney and liver, respectively. Only in one liver metastasis was a mutation identified that was neither present in the primary lung tumor nor in a kidney metastasis, suggesting that occasionally p53 mutations occur after metastatic spread.

Aged↗
PubMed1993

Mutations of the p53 tumor suppressor gene in neoplasms of the human nervous system.

A variety of neoplasms of the human nervous system were analyzed for the presence of mutations in the p53 tumor suppressor gene. DNA was extracted from frozen or formalin-fixed, paraffin-embedded material. Single-strand conformation polymorphism (SSCP) analysis for exons 5-8 was followed by direct DNA sequencing. Mutations leading to an amino acid change were found in three of 11 (27%) low-grade (World Health Organization (WHO) Grade II) astrocytomas. They were located in codon 183 (TCA-->TGA) of exon 5, codon 237 (ATG-->ATA) of exon 7, and codon 273 (CGT-->CAT) of exon 8. In one of these cases, the sequence indicated loss of the wild-type allele. Of 12 juvenile pilocytic astrocytomas (WHO Grade I), none contained a p53 mutation, suggesting a different molecular basis for this childhood neoplasm. Except for a mutation in one of seven (14%) meningeal hemangiopericytomas (codon 238; TGT-->TTT, Cys-->Phe), no mutations were observed in exons 5-8 of the p53 gene in any of the following tumors of the nervous system and its coverings: 13 schwannomas, 12 central neurocytomas, 22 meningiomas, 10 choroid plexus papillomas and carcinomas, and 30 neuroblastomas of the sympathetic nervous system. These and published data support the view that p53 mutations are frequently involved both in low-grade and progressive (anaplastic) astrocytomas, including glioblastomas multiforme. Oligodendrogliomas, medulloblastomas, meningiomas, and hemangiopericytomas rarely (< 15%) show p53 mutations in exons 5-8, whereas none of the remaining nervous system neoplasms revealed evidence of an involvement of the p53 gene in their development.

Adolescent↗
PubMed1993

Deletions on the long arm of chromosome 17 in pilocytic astrocytoma.

Pilocytic astrocytomas are the most common astrocytic tumors of childhood and differ clinically and histopathologically from those astrocytomas that affect adults. Studies of adult astrocytic tumors have revealed allelic losses on chromosomes 10, 17p, 19q and alterations in the epidermal growth factor receptor (EGFR) gene. We have previously examined pilocytic astrocytomas for allelic losses on chromosomes 10 and 19q and for amplification of the EGFR gene, but did not detect genomic alterations at these loci. In the present study we assayed 20 pilocytic astrocytomas for loss of allelic heterozygosity of chromosome 17p, including one locus in the p53 tumor suppressor gene. In addition, because pilocytic astrocytomas frequently affect patients with neurofibromatosis type 1 (NF1) and the NF1 gene has been mapped to 17q11.2, we also examined multiple loci on the long arm of chromosome 17. Allelic loss was observed on chromosome 17 in four cases (three sporadic, one NF1); all lost portions of the long arm in chromosome 17, and one tumor lost the short arm as well. One tumor showed an interstitial deletion on the long arm that included the region of the NF1 gene. These data suggest the presence of a tumor suppressor gene on 17q that is associated with pilocytic astrocytomas. A potential candidate for this gene is the NF1 tumor suppressor gene.

Adolescent↗
PubMed1993

p53 mutations in phenacetin-associated human urothelial carcinomas.

Chronic abuse of the analgesic drug phenacetin is associated with an increased risk of development of transitional cell carcinomas of the urinary tract. It is unclear whether phenacetin acts through chronic tissue damage (phenacetin nephropathy) or via a genotoxic metabolite causing promutagenic DNA lesions. In the present study, we investigated 15 urothelial carcinomas from 13 patients with evidence of phenacetin abuse. Tumors were screened for p53 mutations in exons 5-8 by single-strand conformation polymorphism (SSCP) analysis, followed by direct sequencing of PCR-amplified DNA. p53 Mutations were detected in 8/14 primary tumors (57%). All except one were missense mutations located in exon 5 (three mutations), exon 6 (one), exon 7 (two) and exon 8 (one). The type of mutation varied, with a preference for CpG sites. A frameshift mutation resulting from the insertion of a single cytosine at codons 151/152 was detected in a bladder tumor and its lung metastasis. Urothelial carcinomas located in the renal pelvis and in the ureter of the same patient exhibited two different mutations, strongly suggesting that they developed independently. Another patient had tumors in the renal pelvis and bladder, both of which contained the same p53 mutation, indicating intracavitary metastatic spread. This demonstrates that screening of p53 mutations allows the clonal origin of tumors in patients with multiple primary and metastatic lesions to be determined. None of the tumors investigated contained mutations in codons 12, 13 or 61 of H-ras or K-ras protooncogenes.

Aged↗
PubMed1993

Complementary tumor induction in neural grafts exposed to N-ethyl-N-nitrosourea and an activated myc gene.

Using a combination of transplacental carcinogen exposure and retrovirus-mediated oncogene transfer into fetal brain transplants, we have studied complementary transformation by N-ethyl-N-nitrosourea (NEU) and the v-myc oncogene in the nervous system. Previous experiments had demonstrated that both agents will not induce tumors independently whereas simultaneous expression of v-H-ras and v-gag/myc exerted a powerful transforming potential in neural grafts. In order to identify other genetic alterations that co-operate with an activated myc gene, the neurotropic carcinogen NEU was used to generate mutations of cellular genes. On embryonic day 14 (ED14), pregnant donor animals (F344 rats) received a single i.v. dose of NEU (50 mg/kg). Twenty-four hours later (ED15), the fetal brains were removed, triturated and incubated with a retroviral vector carrying the v-gag/myc oncogene. Subsequently, these primary cell suspensions were transplanted stereotactically into the caudate-putamen of syngenic adult recipients. After latency periods of 3-6 months, 5 of 10 recipients harboring ED15 fetal brain transplants developed malignant, poorly differentiated neuroectodermal tumors in the grafts. No tumor development was observed in seven recipients harboring ED16 neural grafts. Cell lines were established from three tumors and the 110 kd gag/myc fusion protein encoded by the retroviral construct was identified in the tumors by Western blotting. Several candidate genes for mutational activation by NEU including the H-ras, K-ras and neu oncogenes were analyzed for specific point mutations by polymerase chain reaction (PCR) and direct DNA sequencing of the PCR products. However, no mutations were found in any of these genes. These findings lend further support to the multistep hypothesis of neoplastic transformation in the brain. The tumors induced in this model provide an interesting tool for the identification of genes that co-operate with an activated myc gene in neurocarcinogenesis.

Animals↗
PubMed1993

[p53 mutation in phenacetin-induced urothelial carcinomas].

We investigated 16 urothelial carcinomas from 13 patients with evidence of phenacetin abuse for p53 mutations by single-strand conformation polymorphism (SSCP) analysis and direct DNA sequencing. p53 mutations were detected in 8 of 14 primary tumors (57%). Missense mutations were located in exon 5 (3 mutations), exon 6 (1), exon 7 (2) and exon 8 (1). An insertion of a single cytosine in exon 5 was detected in a bladder tumor and its lung metastasis. In one patient, urothelial carcinomas in the renal pelvis and in the ureter exhibited two different mutations, strongly suggesting that these tumors developed independently. In contrast, the tumors in the renal pelvis and bladder of another patient contained the same mutation, indicating intracavitary metastatic spread. Our data support the view that phenacetin causes urothelial carcinomas through chronic tissue damage rather than promutagenic DNA lesions.

Aged↗
PubMed1992

Evidence for a tumor suppressor gene on chromosome 19q associated with human astrocytomas, oligodendrogliomas, and mixed gliomas.

Previous studies have shown frequent allelic losses of chromosomes 9p, 10, 17p, and 22q in glial tumors. Other researchers have briefly reported that glial tumors may also show allelic losses of chromosome 19, suggesting a putative tumor suppressor gene locus on this chromosome (D. T. Ransom et al., Proc. Am. Assoc. Cancer Res., 32:302, 1991). To evaluate whether loss of chromosome 19 alleles is common in glial tumors of different types and grades, we performed Southern blot restriction fragment length polymorphism analysis for multiple chromosome 19 loci in 122 gliomas from 116 patients. Twenty-nine tumors had loss of constitutional heterozygosity of 19q, and four tumors had partial deletions of 19q. Allelic losses on 19q were restricted to grade III anaplastic astrocytomas (4/9) and grade IV glioblastomas (11/46), grade II oligodendrogliomas (2/5) and grade III anaplastic oligodendrogliomas (2/2), and grade II (5/8) and grade III (5/7) mixed oligoastrocytomas. These data demonstrate genetic similarities between astrocytomas, oligodendrogliomas, and mixed glial tumors and indicate the presence of a glial tumor suppressor gene on chromosome 19q.

Astrocytoma↗
PubMed1992

p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma.

Loss of genetic material on the short arm of chromosome 17 is observed in approximately 40% of human astrocytomas (WHO grades II and III) and in approximately 30% of cases of glioblastoma multiforme (WHO grade IV). Previous studies of glioblastoma multiforme have shown that the p53 gene, located on the short arm of chromosome 17, is frequently mutated in these glioblastomas. To explore whether lower-grade astrocytomas are also associated with corresponding mutations of the p53 gene, we have investigated a series of 22 human astrocytomas of WHO grades II and III both for loss of heterozygosity on chromosome 17p and for p53 mutations. Mutations in the conserved regions of the p53 gene were identified by single strand conformation polymorphism analysis of exons 5, 6, 7, and 8 and were verified by direct DNA sequencing of the polymerase chain reaction products. p53 mutations were observed in 3 of 8 grade II astrocytomas and 4 of 14 grade II astrocytomas. In all 22 tumors, allelic loss of the short arm of chromosome 17 was investigated by restriction fragment length polymorphism analysis. One-half of the grade II astrocytomas (4 of 8) and grade III astrocytomas (7 of 14) exhibited allelic loss on chromosome 17p. Mutations in the p53 gene were exclusively observed in tumors with allelic loss on 17p. Our results show that p53 mutations are not restricted to glioblastoma multiforme and may be important in the tumorigenesis of lower-grade astrocytomas and that p53 mutations in lower-grade astrocytomas are associated with loss of chromosome 17p. These findings are consistent with a recessive mechanism of action of p53 in WHO grade II and III astrocytoma tumorigenesis.

Alleles↗
PubMed1992

Association of epidermal growth factor receptor gene amplification with loss of chromosome 10 in human glioblastoma multiforme.

Although the loss of tumor suppressor genes and the activation of oncogenes have been established as two of the fundamental mechanisms of tumorigenesis in human cancer, little is known about the possible interactions between these two mechanisms. Loss of genetic material on chromosome 10 and amplification of the epidermal growth factor receptor (EGFR) gene are the most frequently reported genetic abnormalities in glioblastoma multiforme. In order to examine a possible correlation between these two genetic aberrations, the authors studied 106 gliomas (58 glioblastomas, 14 anaplastic astrocytomas, five astrocytomas, nine pilocytic astrocytomas, seven mixed gliomas, six oligodendrogliomas, two ependymomas, one subependymoma, one subependymal giant-cell astrocytoma, and three gangliogliomas) with Southern blot analysis for loss of heterozygosity on both arms of chromosome 10 and for amplification of the EGFR gene. Both the loss of genetic material on chromosome 10 and EGFR gene amplification were restricted to the glioblastomas. Of the 58 glioblastoma patients, 72% showed loss of chromosome 10 and 38% showed EGFR gene amplification. The remaining 28% had neither loss of chromosome 10 nor EGFR gene amplification. Without exception, the glioblastomas that exhibited EGFR gene amplification had also lost genetic material on chromosome 10 (p less than 0.001). This invariable association suggests a relationship between the two genetic events. Moreover, the presence of 15 cases of glioblastoma with loss of chromosome 10 but without EGFR gene amplification may further imply that the loss of a tumor suppressor gene (or genes) on chromosome 10 precedes EGFR gene amplification in glioblastoma tumorigenesis.

Biomarkers, Tumor↗