Search PubMed⌕ Search

Biomedical subjects

H Christiansen

Publications and source records attributed to H Christiansen.

At least 55 records · Page 3Linked to original sources

Comparison of DNA aneuploidy, chromosome 1 abnormalities, MYCN amplification and CD44 expression as prognostic factors in neuroblastoma.

A comparison of the prognostic impact of five molecular variables in a large series was made, including tests of their nonrandom association and multivariate analysis. Molecular data were available for 377 patients and MYCN amplification, cytogenetic chromosome 1p deletion, loss of chromosome 1p heterozygosity, DNA ploidy and CD44 expression were investigated. Their interdependence and influence on event-free survival was tested uni- and multivariately using Pearson's chi 2-test, Kaplan-Meier estimates, log rank tests and the Cox's regression model. MYCN amplification was present in 18% (58/322) of cases and predicted poorer prognosis in localised (P < 0.001), metastatic (P = 0.002) and even 4S (P = 0.040) disease. CD44 expression was found in 86% (127/148) of cases, and was a marker for favourable outcome in patients with neuroblastoma stages 1-3 (P = 0.003) and 4 (P = 0.017). Chromosome 1p deletion was cytogenetically detected in 51% (28/55), and indicated reduced event-free survival in localised neuroblastoma (P = 0.020). DNA ploidy and loss of heterozygosity on chromosome 1p were of less prognostic value. Most factors of prognostic significance were associated with each other. By multivariate analysis, MYCN was selected as the only relevant factor. Risk estimation of high discriminating power is, therefore, possible for patients with localised and metastatic neuroblastoma using stage and MYCN.

Aneuploidy↗

Differentiation and prognosis of neuroblastoma in correlation to the expression of CD44s.

Cell-cell and cell-extracellular matrix interactions mediated by cell adhesion molecules (for example CD44) play an important role in the cascade of metastasis and the progression of human malignant tumours. The most important aim of this review was, on the basis of our results and the literature, to show the correlation between the expression of CD44s and differentiation and prognosis of neuroblastoma. Surprisingly and in contrast to most other malignant tumours, neuroblastomas exhibited an inverse correlation between CD44s expression and tumour progression. It can be stated that CD44s is a prognostic marker in neuroblastoma which correlates significantly with the grade of tumour cell differentiation, but not with clinical stage. Moreover, there exists a statistically significant correlation between MYCN oncogene amplification and the lack of CD44s expression.

Antigens, Neoplasm↗

Porcine VEG proteins and tear prealbumins.

Small soluble proteins, belonging to the lipocalin family are secreted in large amounts by tongue von Ebner's glands and lachrymal glands. In humans, the lingual protein, called VEG, and the lachrymal protein, called tear prealbumin, have shown identical cDNA sequences. In the pig, we have purified homodimeric proteins with subunits of 17 kDa, both from von Ebner's glands and from lachrymal glands. In both cases, the proteins can be resolved into two isoforms on a chromatofocusing column. Partial aminoacid sequences and full cDNA sequences have been obtained for the more abundant forms purified from both tissues. The two proteins appear to be identical, as in humans. The reason why the same protein is expressed in different tissues, as well as its physiological function, still remain to be clarified.

Amino Acid Sequence↗

Applied Sciences: Absence of CD44-standard in human neuroblastoma correlates with histological dedifferentiation, N-myc amplification and reduced survival probability.

Expression of CD44 was examined by immunohistochemistry in 205 primary neuroblastomas together with histological grading according to the Shimada classification at the time of diagnosis. In addition, Southern blot analysis to determine N-myc gene amplification was carried out in the same tissue. When compared with clinical data such as stage, age and event-free survival probability it was found that CD44 expression characterizes well differentiated tumours and thus correlates with prognosis (event-free survival probability in CD44 positive patients 0.6 (n = 129) vs. 0.0 (n = 21) in CD44 negative patients). In tumours with N-myc = 1, CD44 positivity was found in 91% of patients as compared to 57% of patients with N-myc > 1 in tumours. All tumours of 13 patients with metastatic stage 4s (with good prognosis) showed CD44s expression. Thus, detection of CD44s expression might serve as a prognostic indicator which can be rapidly detected at diagnosis.

Journal Article↗

[Patient-related color preference and color design in the hospital].

Colour-physiological studies involving volunteers and colour-psychological interviewing of patients with varied diagnoses revealed that, currently, no compelling scientific reasons can be given for coloration in the hospital. Interviewing 68 patients from a number of clinics on the coloration of sick-rooms yielded the following preferred colours, irrespective of the patients' classing into groups by various criteria: Light colours were consistently preferred for all objects such as ceiling, walls, floor, curtains, furniture, and bed linen. It should be emphasized that even white was a desirable colour for ceilings and bed linen. Beige was found to rank first for walls, floors, curtains, and furniture, whereas the colours of wood and grey shared the second rank for floors and furniture. Green and pink ranked second for bed linen. White and green ranked second for walls and curtains, respectively. In view of the heterogeneity, the findings may not be converted into an absolute just as the recommendations by other workers. Still, the patients' wish should be given priority over decreed recommendations by experts when basic considerations of illumination (reflectance!) are allowed for in the particular overall colour design project.

Color↗

Loss of the putative tumor suppressor-gene locus 1p36 as investigated by a PCR-assay and N-myc amplification in 48 neuroblastomas: results of the German Neuroblastoma Study Group.

48 primary neuroblastomas have been examined for an amplified N-myc and loss of the putative tumor suppressor-gene locus 1p36 by loss of heterozygosity studies (LOH 1p36). In 25% of these tumors N-myc amplification and/or a LOH 1p36 was detected, and these patients had a bad prognostic clinical outcome. 75% of the tumors neither had an amplified N-myc nor a LOH 1p36, and these patients had a much better prognosis. Thus, tumor genetic changes can subdivide two types of neuroblastoma with profound different clinical behavior. Detection of these genetic changes at diagnosis could help in front-line risk adapted therapy stratifications in neuroblastoma.

Base Sequence↗

Clinical impact of chromosome 1 aberrations in neuroblastoma: a metaphase and interphase cytogenetic study.

Neuroblastoma tumors are characterized by aberrations of chromosome 1. Rapid detection of these chromosomal aberrations at diagnosis could give important clues to outcome and therapy. We attempted to detect numerical and structural aberrations of chromosome 1 not only by classical metaphase cytogenetics but also by interphase cytogenetics in order to overcome difficulties of karyotyping due to diminished metaphase quality and quantity in primary neuroblastoma samples. Karyotypic changes of chromosome 1 in 53 primary neuroblastomas were evaluated. In addition, we successfully performed interphase cytogenetics using single and double in situ hybridization procedures with chromosome 1-specific repetitive DNA probes on nuclei preparations obtained from 46 and 20 tumors, respectively. Polysomies of structurally normal chromosomes 1 were predominantly seen in tumors with good prognosis, whereas deletions of 1p material were nearly exclusively confined to progressive tumors. Numerical and structural chromosome 1 aberrations as studied by metaphase and interphase cytogenetics are thus valuable prognostic markers in neuroblastoma.

Chromosome Deletion↗

Translocation (5;22) in an Askin's tumor.

A boy with a brain metastasis of an Askin's tumor was investigated. Cytogenetic studies revealed a near-diploid karyotype with monosomies of chromosomes 5 and 22 in the presence of a derivative chromosome der(5)t(5;22)(q35;q11). In particular, no involvement of chromosome 11 was seen.

Brain Neoplasms↗

Possible role for salivary gland protein in taste reception indicated by homology to lipophilic-ligand carrier proteins.

Sensory transduction in taste and olfaction, the principal chemical senses, seems to be mediated by membrane-associated proteins on the apical surfaces of the respective receptor cells. The recent isolation and characterization of soluble 'odorant-binding proteins' secreted from the nasal glands of rat, cow and frog, led to the hypothesis that these proteins function as necessary cofactors in olfactory transduction by concentrating and delivering odorants to the receptors. The primary reception of taste stimuli occurs in specialized neuroepithelial receptor cells bundled in taste buds that are clustered in various types of papillae in the lingual epithelium of the tongue. Small tubulo-alveolar salivary glands, the von Ebner's glands, are located beneath the circumvallate and the foliate papillae. Their ducts open exclusively into the trough at the base of the papillae. Taste buds located in the medial and lateral walls of the papillae open with their taste pores into the trough and consequently are in direct contact with the secretions of von Ebner's glands. Here we report the molecular cloning and characterization of a protein of relative molecular mass 18,000 that is highly expressed in von Ebner's glands. Like the odorant-binding proteins, this protein shows similarity to members of a protein superfamily of hydrophobic molecule transporters, indicating that pre-receptor events could also be necessary for the concentration and delivery of sapid molecules in the gustatory system, and emphasizing the close relationship of taste and olfaction.

Amino Acid Sequence↗

Neuroblastoma: inverse relationship between expression of N-myc and NGF-r.

12 primary neuroblastomas (NB) of different maturation stages, 2 ganglioneuromas (GN), and 2 neuroblastoma cell lines were analysed for RNA expression of the protooncogene N-myc and the gene encoding the nerve growth factor receptor (NGF-r) by Northern-blots, RNA-dot-blots and for receptor presence by immunohistological procedures. In 4 tumors with strongly elevated RNA expression of N-myc the NGF-r RNA expression was weak or absent. In all 8 tumors with highly increased NGF-r transcription no N-myc expression was detectable. These results, indicating an inverse relationship between N-myc and NGF-r expression, could help in establishing markers for differentiation, and thus prognosis, in neuroblastoma.

Blotting, Southern↗

[Tumor cytogenetics and prognosis in neuroblastoma].

In 40 children with neuroblastoma of different clinical stages the tumorkaryotype was determined at onset (n = 30) or at relapse (n = 10) of disease after short-term culture of tumor tissues or bone marrow aspirates. None of the 10 stage I, II, and IVs tumors revealed a chromosome 1p aberration, in contrast to stage III and IV tumors where this abnormality was encountered in 25 (=83%) of 30 patients. Amplification of the proto-oncogene N-myc in the tumor-DNA could not be detected in stage I, II and IVs, was however present in 53% of stage III and IV tumors. Cytogenetic phenomena of gene amplification such as Double minutes (DMs) and Homogeneously Staining Regions (HSRs) correlated with N-myc amplification. About 50% of stage III and IV tumors had chromosome numbers in the neardiploid range whereas prognostically favourable tumors were characterized by hyperploid chromosomal numbers mainly in the triploid range. Life-table analysis according to Kaplan-Meier showed a probability of surviving in about 80% of patients with a normal morphology of chromosome 1 in their tumor cells, compared to about 60% in the absence of N-myc oncogene amplification and of about 50%, if aneuploidy is detected. Thus, we think, the presence or absence of chromosome 1p aberration in the tumorkaryotype is the most sensitive discriminator for outcome in children with neuroblastoma.

Aneuploidy↗

N-myc amplification at chromosome band 1p32 in neuroblastoma cells as investigated by in situ hybridization.

Chromosome deletion at the short arm of one chromosome 1 (1p32)--the most common aberration in neuroblastoma cells--was found to be combined with the generation of a homogeneously staining region at this specific site in a newly established neuroblastoma cell line (GI-LI-N) from a stage IV neuroblastoma. By in situ hybridization this homogeneously staining region was shown to contain multiple copies of the proto-oncogene N-myc. This 30-fold oncogene amplification was confirmed by Southern-blot and DNA-dot-blot analyses. In two additional cell lines from children with stage IV neuroblastoma (GI-ME-N and GI-CA-N) N-myc amplification was not detected. Chromosome 1, however, was involved in a structural rearrangement in one cell line (GI-ME-N).

Child, Preschool↗

Identical chromosome 1p breakpoint abnormality in both the tumor and the constitutional karyotype of a patient with neuroblastoma.

A 4-year-old boy with a stage III abdominal neuroblastoma was studied. Direct chromosome preparation revealed a t(1;?)(p36;?) in three tumor metaphases (one with a chromosome number of 64). After partial resection of the tumor and further tumor shrinkage by intensive combination chemotherapy, the residual tumor mass was removed by a "second-look" operation, and the patient received postoperative radiotherapy to the tumor area. Chromosome analysis from the peripheral blood taken at that time showed tetraploidy in 14% and hypodiploidy in 66% of 50 available metaphases. Structural abnormalities, mainly involving the distal short arm of chromosome 1, could be identified in seven metaphases. A t(1;?)(p36;?) in a diploid blood cell looked identical to the translocation found in the hyperdiploid tumor metaphase. A del(1)(p36) was also found in a blood cell. It is suggested that an association exists between a chromosome fragility at 1p36, in this case postoperatively induced in vivo by chemoradiotherapy, and the development of neuroblastoma.

Abdominal Neoplasms↗

Tumour karyotype discriminates between good and bad prognostic outcome in neuroblastoma.

In 28 patients with neuroblastoma of different stages the karyotype was determined in the primary tumour and/or in the metastases by direct chromosome preparation or short term cell culture. In addition, DNA analysis for the proto-oncogene N-myc was performed for comparison in 10 cases. Abnormalities (deletions, translocations, derivations) of the short arm of chromosome 1 with the most frequent breakpoint at 1p32 (besides rarer aberrations in other chromosomes) were found in the tumour karyotype of 15 of 18 (83%) patients with metastatic disease (stage IV) and in 2 of 3 patients with stage III, but in none of the 7 patients with stages I, II, IV-S who are all alive with no evidence of disease. These 7 surviving patients with good prognosis had a hyperploid tumour karyotype, mainly in the triploid range. Eleven of the 18 (61%) patients with stage IV and 1 of 3 patients with stage III also contained double minutes (DMs) and/or homogeneously staining regions (HSRs) in their tumour karyotypes. N-myc amplification (30 to 60 copies) in the tumour DNA was detected in 2 of 6 (33%) examined cases with stage IV, in 1 out of 2 examined cases with stage III, and correlated with the presence of DMs/HSRs. Life table analysis showed a 90% probability of surviving in patients lacking the 1p abnormality as compared to less than 10% in patients with an aberrant 1p chromosome in the tumour cells. We conclude that tumour karyotype, in particular the structure of the short arm of chromosome 1, is the most important factor in determining the different outcome in children with neuroblastoma.

Chromosome Aberrations↗