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A Dalen

Publications and source records attributed to A Dalen.

At least 19 recordsLinked to original sources
PubMed2005

Immunohistochemical detection of epidermal growth factor receptor in human high-grade astrocytomas--a comparison between frozen- and paraffin sections.

The overexpression of epidermal growth factor receptor (EGFR) in human astrocytic tumours is associated with the oncogenesis of these tumours. Ongoing research on diagnostic, prognostic, and therapeutic aspects of this receptor is highly dependent on the development of reliable techniques for the detection of EGFR in tumour tissue. The aim of this study was to assess EGFR expression in human high-grade astrocytomas by means of immunohistochemistry on formalin-fixed, paraffin-embedded sections and to compare these findings with the results of our previous study on frozen sections from these tumours, in which we found about 60% EGFR positivity (10). Four anaplastic astrocytomas and 19 glioblastomas were included in this study. Two different antibodies were used, the monoclonal antibody E30 reactive against the extracellular domain of EGFR and the polyclonal antibody Ab-4 directed against its cytoplasmic domain. With E30, 3 out of 4 anaplastic astrocytomas (75%) and 12 out of 19 glioblastomas (63%) were found to express EGFR whereas Ab-4 demonstrated positive EGFR immunoreactivity in most of the tumours (18/19 glioblastomas and all the 4 anaplastic astrocytomas). In conclusion, immunohistochemistry represents a reliable and convenient technique for the detection of EGFR in tissue sections of human high-grade astrocytomas, and that EGFR immunoreactivity is comparable in frozen- and paraffin sections from these tumours.

Astrocytoma↗
PubMed2003

Anogenital human papillomavirus in non-abused preschool children.

AIM: To estimate the prevalence of human papillomavirus (HPV) in anogenital samples from children selected for non-abuse. METHODS: A letter of invitation was sent to 2731 girls and 1042 boys, all of them aged 5 or 6 y. Inclusion was based on self-selection, whereby parents who did not suspect any occurrence of sexual abuse of their child gave informed consent to participate. Several mechanisms were undertaken to exclude abused children. A complete examination was done of each child, including anogenital examination with a colposcope and microbiological sampling from the genitals and anus. Polymerase chain reaction (PCR) using primers MY09 and MY11 was used to identify HPV, and sequencing was done on each positive amplicon. RESULTS: PCR was performed on 325 adequate specimens from 211 children enrolled. Seven samples from 5 girls were HPV-positive, making 2/161 (1.2%) of the anal and 5/164 (3.0%) of the genital specimens positive. HPV was not detected in any of the boys. In four girls strong associations with HPV 6 genotypes were found, while one girl probably had a mixed infection with HPV 6 and 16. Three girls (1.8%) had clinically detectable anogenital warts. CONCLUSION: Since our results are comparable with a prevalence reported from allegedly abused children, and higher rates have been reported from the oral cavity in healthy children, we find detection of HPV unreliable as an indicator of sexual abuse in 5-6-y-old children. The rate of anogenital warts found in our study is comparable with a rate reported in abused children.

Anal Canal↗
PubMed1998

Identification of genetic determinants responsible for the rapid immunosuppressive activity and the low leukemogenic potential of a variant of Friend leukemia virus, FIS-2.

An immunosuppressive variant of Friend murine leukemia virus (F-MuLV), FIS-2, induces suppression of the primary antibody response against sheep erythrocytes (SRBC) in adult NMRI mice more efficiently than the prototype F-MuLV clone 57 (cl.57). It is, however, less potent than F-MuLV cl.57 in inducing erythroleukemia upon inoculation into newborn NMRI mice. Nucleotide sequence analysis shows a high degree of homology between the two viruses. Single point mutations are scattered over both the gag and the env encoding regions. The most notable mutations are the deletion of one direct repeat and a few single point mutations occurring in the binding sites for cellular transcriptional factors in the FIS-2 long terminal repeat region (LTR). To define the genetic determinants responsible for the pathogenic properties of FIS-2, we constructed six chimeras between FIS-2 and F-MuLV cl.57. Adult mice were infected with the chimeras, and their primary antibody responses against SRBC were investigated. The results showed that the fragment encompassing the FIS-2 env encoding region SU is responsible for the increased immunosuppressive activity in adult mice. A leukemogenicity assay was also performed by infecting newborn mice with the chimeras. Consistent with the previous studies, it showed that the deletion of one direct repeat in the FIS-2 LTR is responsible for the long latent period of erythroleukemia induced by FIS-2 in newborn-inoculated mice. However, studies of cell type-specific transcriptional activities of FIS-2 and F-MuLV cl.57 LTRs using LTR-chloramphenicol acetyltransferase constructs showed that the deletion of one direct repeat does not reduce the transcriptional activity of the FIS-2 LTR. The activity is either comparable to or higher than the transcriptional activity of the F-MuLV cl.57 LTR in the different cell lines that we used, even in an erythroleukemia cell line. It seems that the high transcriptional strength of the FIS-2 LTR is not sufficient to give FIS-2 a high leukemogenic effect. This suggestion is inconsistent with the previous suggestion that the transcriptional strength of an LTR in a given cell type is correlated with the leukemogenic potential in the corresponding tissue. In other words, these data indicate that the direct repeats in the F-MuLV LTR may play other roles besides transcriptional enhancer in the leukemogenesis of F-MuLV.

Animals↗
PubMed1996

Papillomatosis of the esophagus.

Esophageal papillomas are rare. Both local irritation as by gastroesophageal reflux and infections with human papillomavirus (HPV) have been implicated as etiological factors. We here describe a 28-year-old female patient with massive esophageal papillomatosis. The clinical course has been mild, with signs of regression after a 3 1/2-year observation period. An extensive evaluation showed no predisposing diseases, and test results for HPV using sensitive methods were negative despite histological features suggesting virus infection and concomitant pharyngeal papillomas that are known to be caused by HPV. This case underlines the incomplete understanding of the etiology of this disease.

Adult↗
PubMed1995

[Virus as an etiological factor of cancer in human beings].

Human oncogenic viruses are heterogenous as a group but share the property of causing persistent and often lifelong infections. Immortalization of host cells is seen in some but not all infections. Chromosomal instability of the infected cells is probably important. Epidemiological data indicate that viral oncogenesis in humans is a multifactorial process where host factors such as age, race, sex and immune-competence, and exogenous factors such as coinfections and cocarcinogens, are important determinants.

Carcinoma↗
PubMed1995

Detection of cytomegalovirus using 'boosted' nested PCR.

As a part of a study of an outbreak of CMV infections in a neonatal care intensive care unit, a modified nested PCR was developed for detection of CMV DNA in clinical specimens. Standard nested PCR involves a critical step; passage of PCR products from the first reaction round to the second round. We have adapted a 'boosted' nested PCR which implies amplification in one single step, thus reducing the contamination problems. Nasopharyngeal aspirates and urine samples from patients with perinatal CMV infections, breast milk from some of their mothers, amniotic fluids, urine samples and lymphocytes from seropositive healthy adults were examined by PCR and culture. In the total of 614 of clinical specimens, the PCR test yielded positive results in 51 samples from 14 patients, whereas CMV was isolated in 25 samples from 11 cases only. All samples from healthy individuals were negative. CMV DNA was detected in all culture-positive samples, but all samples from healthy adults were negative. 29/68 culture negative specimens were positive by PCR. No cross-reactivity to other herpes viruses or to human DNA was observed. Our findings show a high sensitivity and a high specificity of the 'boosted' nested PCR. We conclude that the described PCR method can be used for the rapid detection of CMV in clinical specimens with a greatly reduced risk of contamination, and it has proved to be a very useful tool in diagnostic work.

Adult↗
PubMed1995

An immunosuppressive murine leukaemia virus induces a Th1-->Th2 switch and abrogates the IgM antibody response to sheep erythrocytes by suppressing the production of IL-2.

Many retroviruses have tropism for cells in the immune system and have a propensity to induce immunosuppression in the host. Some of the effects of retroviruses on immune cell function are thought to be mediated through cytokines. Friend ImmunoSuppressive virus-2 (FIS-2) is a low oncogenic murine leukaemia virus (MuLV) that induces lymphadenopathy and immunosuppression in NMRI mice. The role of T cell cytokines during the generation of a primary antibody response in healthy and FIS-2-infected mice was studied following the antibody response to sheep erythrocytes by an in vitro immunization (IVI) technique. In cultures from FIS-2-infected mice, the antibody response was reduced compared with cultures from uninfected mice and the production of the Th2 cytokines IL-4 and IL-6 was elevated, whereas the Th1 cytokines IL-2, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were reduced. The suppressed anti-sheep erythrocyte antibody response in cultures from mice infected with FIS-2 seemed to be caused by an insufficient production of IL-2, since addition of recombinant IL-2 stimulated the antibody response. This effect was also observed in cultures depleted of T cells, indicating a direct effect of IL-2 on B cells. A switch to a Th2 cell response and suppression of IL-2 production might play a central role in the immune cell dysfunction induced by FIS-2.

Animals↗
PubMed1994

Molecular cloning and characterization of an immunosuppressive and weakly oncogenic variant of Friend murine leukemia virus, FIS-2.

The FIS variant is a weakly leukemogenic, relatively strong immunosuppressive murine retrovirus which was isolated from the T helper cells of adult NMRI mice infected with Friend murine leukemia virus (F-MuLV) complex (FV). Unlike FV, it does not induce acute erythroleukemia but retains the immunosuppressive property of FV and induces suppression of the primary antibody response rapidly and persistently in adult mice. A previous study showed that the FIS variant contains two viral components, a replication-competent virus and a defective virus. In this study, we have biologically purified the FIS variant by end point dilution and we show that the replication-competent virus FIS-2 alone can induce immunosuppression as the parental FIS variant. Most newborn mice infected with FIS-2 developed erythroleukemia, but with an increased latency period compared with that of F-MuLV clone 57. In contrast, FIS-2 induced suppression of the primary antibody response and disease more rapidly than F-MuLV clone 57 in immunocompetent, adult mice. FIS-2 was further molecularly cloned and characterized. Restriction mapping and nucleotide sequence analysis of FIS-2 showed a high degree of homology between FIS-2 and F-MuLV clone 57, suggesting that FIS-2 is a variant of F-MuLV. The striking difference is the deletion of one of the tandem repeats in the FIS-2 long terminal repeat and the single point mutation in the binding sites for core-binding protein and FVa compared with the long terminal repeat of F-MuLV clone 57. Two single point mutations led to the appearance of two extra potential N glycosylation sites in the FIS-2 gag-encoded glycoprotein. Together, the results suggest that FIS-2 represents an interesting murine model to study retrovirus-induced immunosuppression on the basis of its unique combined property of low leukemogenicity and relatively strong and persistent immunosuppressive activity in adult mice.

3T3 Cells↗
PubMed1993

Multiple derangements of cytokine homeostasis in mice infected with immunosuppressive retrovirus.

Altered production of various lymphokines is considered an important factor in retrovirus-induced immunosuppression. We have measured the production of interleukin 2 (IL-2), interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-beta 1), and tumor necrosis factor alpha (TNF-alpha) in splenocytes of retrovirus-infected NMRI mice. In Con A-stimulated splenocytes from mice infected with the acute transforming retrovirus Friend leukemia complex (FLC), TNF-alpha and IL-6 production was significantly suppressed. We compared cytokine production in infection with Friend-derived murine immunosuppressive virus (Fd-MIV), a low oncogenic retrovirus that induces a immunosuppression of a magnitude similar to that of FLC. In Fd-MIV infection, the ability of lymphoid cells to produce both IL-2 and TNF-alpha was suppressed. The suppression of these cytokines coincided with the suppression of the primary antibody response. In contrast to FLC infection, the production of IL-6 was elevated. Furthermore, increased production of TGF-beta was found in unstimulated splenocytes from Fd-MIV-infected mice. Infection with immunosuppressive retroviruses induces a complex derangement of T-cell cytokine homeostasis and the relative contributions of the various factors to the immunosuppressed state are difficult to assess at present.

Animals↗
PubMed1993

C-erbB-2/HER-2 protein in human intracranial tumours.

Normal and neoplastic human intracranial tissues were examined by immunohistochemistry for c-erbB-2/HER-2 protein expression. Positive staining was observed in 1/41 gliomas, 1/2 medulloblastomas, 1/1 germinoma, 11/16 meningiomas, 1/3 anaplastic meningiomas and 11/19 metastatic brain carcinomas. No positive staining was observed in normal intracranial tissues. Thus, the expression of the c-erbB-2/HER-2 protein is limited to intracranial tumour tissues, principally meningiomas and metastatic carcinomas to the brain.

Adult↗
PubMed1992

Relationships between Ki-67 labelling index, amplification of the epidermal growth factor receptor gene, and prognosis in human glioblastomas.

The aim of this study was to determine possible relationships between Ki-67 labelling index (Ki-67 LI), amplification of the epidermal growth factor receptor (EGFR) gene, and prognosis in human glioblastomas. Ki-67 LI was determined on cryosections of biopsy specimens of 20 human glioblastomas with a mouse anti-human Ki-67 monoclonal antibody. Amplification of the EGFR gene was determined by slot blot and Southern blot analyses of DNA extracted from the tumour biopsies. The Ki-67 LI was higher in the glioblastoma group with EGFR gene amplification (8 tumours, median value of Ki-67 LI 4.2, range 0.4-24.6) than in those without EGFR gene amplification (12 tumours, median value of Ki-67 LI 0.8, range 0.2-11.8) (0.05 p less than 0.1). The glioblastoma patients with Ki-67 LI greater than 1.5 (10 tumours) had a statistically significant shorter survival than those with Ki-67 LI less than 1.5 (10 tumours) (p less than 0.05). The glioblastoma patients with EGFR gene amplification lived shorter time than those without EGFR gene amplification (p greater than 0.05).

Actuarial Analysis↗
PubMed1992

Expression of the epidermal growth factor receptor gene in human brain metastases.

Biopsy specimens of human brain metastases were examined for amplification and expression of the proto-oncogene c-erbB1 (located on chromosome 7) encoding the epidermal growth factor receptor (EGFR). Moreover, the tumour DNA was also examined for amplification of other cancer-related genes on this chromosome: the proto-oncogene c-met, the gene for platelet-derived growth factor A-chain, and the gene for plasminogen activator inhibitory type 1. All 18 brain metastases demonstrated positive binding of biotinylated EGF on cryosections. Three out of 18 metastases had amplification of the EGFR gene; the other chromosome-7 genes tested were not amplified. Thus, an increased EGFR gene expression seems to be a general finding in a wide range of carcinomas metastatic to the brain, whereas we found only occasional selective EGFR gene amplifications in single cases.

Adult↗
PubMed1992

Expression of epidermal growth factor receptor in human meningiomas and meningeal tissue.

The aim of this study was to examine meningeal tissue under normal, reactive, and neoplastic conditions for expression of epidermal growth factor receptor (EGFR) using an improved histochemical method, namely biotinylated epidermal growth factor. EGFR was found in all the examined meningiomas (12 benign and three anaplastic) and in neonatal rat meninges, whereas normal and injured adult human and rat meninges did not exhibit detectable EGFR. These observations indicate that EGFR is involved in the development of meningeal tissue. Further, EGFR is abnormally expressed in meningeal tumours, indicating a role of EGFR in the neoplastic process of these tumours. The regular expression of EGFR in human meningiomas suggests EGFR as a tumour marker for this tumour type.

Adult↗
PubMed1991

Epidermal growth factor receptor expression in human gliomas.

The expression of epidermal growth factor receptor (EGFR) was determined in cryosections of 42 human gliomas using biotinylated epidermal growth factor (B-EGF) and two monoclonal antibodies (mAb) against EGFR. All gliomas were found to express EGFR when examined with B-EGF, whereas 33 expressed EGFR when examined with the two mAbs. The highly malignant gliomas (glioblastomas and anaplastic astrocytomas) had a more heterogeneous staining strongly with B-EGF than did the low-grade gliomas (astrocytomas, oligodendrogliomas, mixed gliomas, and ependymomas). This indicates that high-grade gliomas contain more tumour cells rich in EGFR than do the low-grade gliomas. Reactive astrocytes, ependymal cells, and many types of nerve cells (cerebral cortical pyramidal cells, pyramidal and granular hippocampal cells, Purkinje cells, cerebellar granular cells and neurons in the molecular layer of the cerebellum) expressed EGFR, whereas small neurons and normal glial cells were not found to express EGFR.

Adult↗
PubMed1990

Polysomy of chromosome 7 is associated with amplification and overexpression of the EGF-receptor gene in a human carcinoma cell line derived from a brain metastasis.

Overexpression of the EGF-receptor gene is associated with the malignant nature of some tumors. We have recently reported the establishment of a human carcinoma cell line (T-CAR1), derived from a brain metastasis, that had 7 million EGF receptors per cell and was growth inhibited by EGF. The present study was carried out in order to further characterize the EGF-receptor protein in T-CAR1 cells, and to see if the overexpression of the EGF-receptor gene in these cells was associated with abnormalities at the genomic level. We have compared the T-CAR1 cells with the human glioblastoma cell line T-MG1, which has 135,000 EGF-receptors and is growth stimulated by EGF. The MW of the EGF receptors in T-CAR1 cells and T-MG1 cells was estimated to be 170 kDa, equal to the normal EGF-receptor. However, in T-CAR1 cells an additional protein reacted with the monoclonal antibody directed against the internal domain of the EGF receptor. The levels of EGF receptor-related RNAs in T-CAR1 cells and T-MG1 cells reflected the number of EGF receptors in these cell lines. The EGF-receptor gene was amplified ten-fold in T-CAR1 cells, while it was not amplified in T-MG1 cells. No restriction fragment length polymorphism of DNA digested with various restriction enzymes was seen in either of the cell lines. Chromosomal analysis of T-CAR1 cells showed polysomy of chromosome 7 and marker chromosomes derived partly from chromosome 7. Thus, in the T-CAR1 cell line it was an association between polysomy of chromosome 7 and EGF-receptor gene amplification.

Aneuploidy↗