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A L Nielsen

Publications and source records attributed to A L Nielsen.

At least 19 recordsLinked to original sources
PubMed1997

[The prognostic significance of progesterone receptor level in endometrial cancer].

Oestrogen receptor (ER) and progesterone receptor (PR) contents were determined by biochemical (dextran charcoal-coated (DCC) assay) and immunohistochemical (ICA) methods in biopsies from 145 primary endometrial adenocarcinomas. Correlations between receptor contents and cancer specific survival were examined in a multivariate analysis including histopathological characteristics. Median patient follow-up time was 67 months with 18 cancer deaths. "High" PR levels correlated significantly (p = 0.004) with survival, independently of stage risk group (stages Ia-Ib vs Ic-IV). Patient age and histological grade were prognostic factors in a univariate setting but these parameters were eliminated in the multivariate model. The association between PR contents and cancer survival suggests that determination of PR can be of importance in the evaluation of endometrial cancer.

Adult↗
PubMed1997

Comparison of the reproducibility of the WHO classifications of 1975 and 1994 of endometrial hyperplasia.

In a blinded, randomized design, six histopathologists with an interest in gynecological pathology examined the inter- and intraobserver variation of the histopathological diagnosis of endometrial hyperplasia according to the World Health Organization (WHO) classification of 1975 and the new WHO classification of 1994. On four occasions, the pathologists assessed hematoxylin/eosin-stained slides from 128 cases originally diagnosed and coded in the Snomed system as endometrial hyperplasia. In the first and third rounds, the slides were classified according to the 1975 classification and in the second and fourth rounds according to the 1994 classification. The overall interobserver agreement in the two rounds where the 1975 classification was used was 0.47 and 0.51, and the kappa values 0.24 [95% confidence interval (CI) 0.21-0.27] and 0.30 (95% CI 0.27-0.33). The overall interobserver agreement in the two rounds using the 1994 classification was 0.45 and 0.41 and the kappa values 0.25 (95% CI 0.23-0.28) and 0.20 (95% CI 0.17-0.22). Reducing the classification to two categories with clinical significance (atypical endometrial hyperplasia versus others in the 1975 classification, and atypical endometrial hyperplasia, complex versus others in the 1994 classification) increased the overall agreement of the 1975 classification in both rounds to 0.91 and of the 1994 classification to 0.92 and 0.90. The kappa values increased to 0.54 (95% CI 0.49-0.58) and 0.49 (95% CI 0.45-0.54) in the 1975 classification and to 0.59 (95% CI 0.54-0.63) and 0.42 (95% CI 0.37-0.46) in the 1994 classification. The intraobserver overall agreement for the 1975 classification ranged from 0.80 to 0.55 and the kappa values from 0.70 (95% CI 0.58-0.81) to 0.28 (95% CI 0.17-0.39). The intraobserver overall agreement for the 1994 classification ranged from 0.71 to 0.46 and the kappa values from 0.60 (95% CI 0.51-0.70) to 0.20 (95% CI 0.09-0.30). It is concluded that there is considerable inter- and intraobserver variation using both the 1975 and the 1994 classifications of endometrial hyperplasia. We propose that there is need for a specification and for a simplification of the classification.

Double-Blind Method↗
PubMed1996

E-box sequence and context-dependent TAL1/SCL modulation of basic helix-loop-helix protein-mediated transcriptional activation.

TAL1/SCL is a basic helix-loop-helix (bHLH) oncoprotein that is expressed in several cell lines including many hematolymphoid cells, but not in T- and B-lineage cells. The TAL1 gene was originally discovered as being transcriptionally activated by chromosomal rearrangements in T-cell acute lymphoblastic leukemia (T-ALL). Here we have shown that TAL1 and the ubiquitously expressed murine bHLH transcription factor ALF1 formed heterodimers that, compared with ALF1 homodimers, had a more restricted E-box specificity and bound preferentially to the glucocorticoid-responsive E-box (Egre) motif (AACAGATGGT). Overexpression of the dominant inhibitory HLH protein Id1 in NIH3T3 cells reduced the transcriptional activity mediated by ALF1 homodimers, whereas the transcriptional activity mediated by TAL1/ALF1 heterodimers was resistant to Id overexpression. Our results show that ALF1 may serve as a dimerization partner for the bHLH oncoprotein TAL1 and form a complex with a distinctive DNA binding property. These findings support the hypothesis that the leukemic characteristics of the TAL1 oncoprotein could be mediated by activation of a set of target genes as heterodimeric complexes with ubiquitously expressed bHLH transcription factors such as ALF1 and that a principal role of TAL1 might be to neutralize an Id-mediated inactivation.

3T3 Cells↗
PubMed1996

A possible involvement of TIF1 alpha and TIF1 beta in the epigenetic control of transcription by nuclear receptors.

Nuclear receptors (NRs) are ligand-inducible transcription factors that mediate complex effects on development, differentiation and homeostasis. They regulate the transcription of their target genes through binding to cognate DNA sequences as homodimers or heterodimers. The molecular mechanisms underlying transcriptional activation by NRs are still poorly understood, although intermediary factors (mediators) appear to be involved in mediating the transactivation functions of NRs. TIF1 has been identified previously as a protein that interacts specifically with the ligand binding domain of several nuclear receptors, both in yeast and in vitro. The characteristics of these interactions have led us to suggest that TIF1 might be a mediator of the NR ligand-inducible activation function AF-2. Using a two-hybrid screening in yeast, we have now identified two TIF1-binding proteins, mHP1 alpha and mMOD1, that are mouse homologues of the Drosophila heterochromatinic protein 1. Using mHP1 alpha as a bait in a second two-hybrid screening, we have isolated cDNAs encoding proteins that are also very likely to be involved in chromatin structure and function, as well as a protein structurally and functionally related to TIF1 (renamed TIF1 alpha), which was named TIF1 beta. Here we discuss how the function of members of the TIF1 family in the control of transcription could be exerted at the level of the structure of the chromatin template.

Amino Acid Sequence↗
PubMed1996

The combination of p53 and age predict cancer specific death in advanced stage (FIGO Ic-IV) of endometrial carcinoma of endometrioid type. An immunohistochemical examination of growth fraction: Ki-67, MIB-1 and PC10; suppressor oncogene protein: p53; oncogene protein: p185 and age, hormone treatment, stage, and histologic grade.

OBJECTIVE: Early surgical stage (FIGO Ia + b) is an excellent predictor of survival in endometrial carcinoma of endometrioid type (EC), in contrast to advanced stage which only predict cancer specific death (CSD) in approximately 20-30% of the patients. The value of growth fraction, p53 and p185 as predictor of CSD in EC was studied. STUDY DESIGN: One hundred and eleven patients (45% hormone-users) with EC were entered prospectively and consecutively into an immunohistochemical study of growth fraction (Ki-67, MIB-1 and PC10), suppressor oncogene protein (p53) and oncogene protein (p185). RESULTS: All markers except p185 intercorrelated significantly, although weakly, however, marked differences were found in median values of the markers of growth fraction (GF). It was shown that immunohistochemical demonstration of p53 and p185 proteins and stage correlates independently with CSD in EC. CONCLUSION: The study indicates that the markers of GF do not give exact information about the proliferative compartment of the EC, and it is shown that p53 correlate to CSD, while stage indicate crude death.

Age Factors↗
PubMed1996

Various modes of basic helix-loop-helix protein-mediated regulation of murine leukemia virus transcription in lymphoid cell lines.

The transcriptionally regulatory regions of the lymphomagenic Akv and SL3-3 murine leukemia retroviruses (MLVs) contain two types of E-box consensus motifs, CAGATG. One type, EA/S, is located in the upstream promoter region, and the other, E(gre), is located in a tandem repeat with enhancer properties. We have examined the requirements of the individual E-boxes in MLV transcriptional regulation. In lymphoid cell lines only, the E(gre)-binding protein complexes included ALF1 or HEB and E2A basic helix-loop-helix proteins. Ectopic ALF1 and E2A proteins required intact E(gre) motifs for mediating transcriptional activation. ALF1 transactivated transcription of Akv MLV through the two E(gre) motifs equally, whereas E2A protein required the promoter-proximal E(gre) motif. In T- and B-cell lines, the E(gre) motifs were of major importance for Akv MLV transcriptional activity, while the EA/S motif had some effect. In contrast, neither E(gre) nor EA/S motifs contributed pronouncedly to Akv MLV transcription in NIH 3T3 cells lacking DNA-binding ALF1 or HEB and E2A proteins. The Id1 protein was found to repress ALF1 activity in vitro and in vivo. Moreover, ectopic Id1 repressed E(gre)-directed but not EA/S-directed MLV transcription in lymphoid cell lines. In conclusion, E(gre) motifs and interacting basic helix-loop-helix proteins are important determinants for MLV transcriptional activity in lymphocytic cell lines.

3T3 Cells↗
PubMed1995

E-box variants direct formation of distinct complexes with the basic helix-loop-helix protein ALF1.

The murine transcription factor ALF1 belongs to the class of basic helix-loop-helix proteins specific for the NCAGNTGN-version of the E-box. Binding of homodimeric ALF1 to variants of this motif was studied by a combination of binding site selection technology and DNA modification interference analysis. The results showed that substitutions at the non-conserved positions in the E-box sequence could cause profound alterations in the patterns of specific contacts at the protein-DNA interface. Thus, both the overall extent of the binding region and the backbone phosphate contact pattern differed markedly between closely related E-boxes with similar affinities for ALF1. The identity of the base at the inner N was an important determinant of contact pattern specification. The E-box variants differed in their ability to mediate ALF1 dependent transcriptional activation in vivo. We discuss the possibility that adaptability in basic helix-loop-helix protein-DNA interactions can result in complexes with different functional properties.

Amino Acid Sequence↗
PubMed1995

Progesterone receptor levels independently predict survival in endometrial adenocarcinoma.

Estrogen receptor (ER) and progesterone receptor (PR) contents were determined by biochemical (dextran charcoal-coated (DCC) assay) and immunohistochemical (ICA) methods in biopsies from 145 primary endometrial adenocarcinomas and those with eligible receptor measurements were analyzed with respect to correlations to cancer-specific survival in a multivariate analysis including histopathological characteristics. Median patient follow-up time was 67 months with 18 cancer deaths. The PR-DCC and ER-DCC values were dichotomized according to levels previously found by us to correspond to the best agreement between receptor status as determined by the DCC and ICA methods (130 fmol/mg cytosol protein for ER, 114 fmol/mg for PR). Using these thresholds, we found by multivariate analysis that "high" PR-DCC levels (> 114 fmol/mg) correlated significantly (P = 0.004) with survival, independent of stage risk group (Ia + b vs Ic-IV). Patient age and histologic grade were prognostic factors in a univariate setting, but these parameters were eliminated in the multivariate model. While the PR-ICA scores also correlated significantly and independently with survival, the predictive effect of PR-ICA positivity alone could not be statistically evaluated due to the number of cases with eligible ICA values. However, we suggest that owing to a close correlation between DCC and ICA results, PR-ICA status may provide significant prognostic information when DCC measurements are not available.

Adenocarcinoma↗
PubMed1995

Evaluation of the optimal duration of chemotherapy in phase II trials for inoperable non-small-cell lung cancer (NSCLC).

PURPOSE: To determine the optimal duration of chemotherapy in phase II trials for patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: The time from start of treatment until achievement of response according to WHO criteria was determined retrospectively in 8 phase II trials. RESULTS: Response to chemotherapy consisting of 4 complete and 39 partial remissions was registered in 43 of 333 patients. The median time from treatment start to response was 54 days. On day 84 on-study, 35 of the responding patients (81%) had achieved the response. Forty-three responses (98%) had occurred by day 168 and only one patient (2%) accomplished a response after 168 days of treatment. The responses had a median duration of 151 days (range 28-1559 days). CONCLUSIONS: The data indicate that patients with NSCLC included in phase II trials who have not yet achieved a response to chemotherapy after 168 days on study have a low likelihood (2%) of a subsequent response. Hence, treatment cessation at this point should be considered for non-responding patients. Continuation of treatment from day 84 to day 168 resulted in response in only 7 patients out of the total of 43 responses noted (16%). Thus, the toxic effects of the chemotherapy in addition to the inconvenience of hospital visits renders it questionable whether it is worthwhile to continue treatment in patients with inoperable non-small-cell lung cancer beyond day 84 in the absence of response.

Adult↗
PubMed1995

Endometrial adenocarcinoma of endometrioid subtype with squamous differentiation: an immunohistochemical study of MIB-1 (ki-67 paraffin), cathepsin D, and C-erbB-2 protein (p185).

Differences in the immunohistochemical expression of Cathepsin D, C-erbB-2 protein (p185), and growth fraction (MIB-1) in glandular and squamous epithelium in adenocarcinoma of endometrioid subtype were studied together with Cathepsin D in macrophages. The findings were correlated with conventional prognostic parameters. A search for human papilloma virus (HPV) (probes 6/11, 16/18, and 31/33/51) by in situ hybridization was also performed. Formalin-fixed and paraffin-embedded tissues from 61 adenocarcinomas with > 10% squamous epithelium were studied. MIB-1 was very low in squamous epithelium, no correlation was found between MIB-1 in squamous and glandular epithelium, and only the glandular epithelium correlated with depth of invasion and stage, indicating that glands are most important with regard to prognosis. Cathepsin D expression in macrophages was significantly increased in advanced stage and may be of prognostic value, but more studies on tissue sections are needed to evaluate the relationship between its expression in tumor cells and other cells. p185 showed no value as a prognosticator. Finally, our study found HPV infrequently in endometrial carcinomas.

Adenocarcinoma↗
PubMed1995

Oxygen status during haemodialysis. The Cord-Group.

Hypoxia during haemodialysis, mainly acetate, has been reported several times. In our study we have monitored oxygen status during 258 bicarbonate haemodialyses. A significant drop below 80 mmHg in mean oxygen tension occurred. Mean oxygen saturation reflected this drop but did not reach levels below 90%. The mean oxygen concentration was on the whole critical low, though slightly increasing during each haemodialysis session due to ultrafiltration. It is concluded that both hypoxia and hypoxaemia do occur during bicarbonate haemodialysis. To a group of patients generally having limited cardiac reserves, a poor oxygen status is a potentially serious complication to haemodialysis. Monitoring oxygen status is thus advisable.

Acetates↗
PubMed1995

Carbon monoxide in chronic uraemia related to erythropoietin treatment and smoking habits.

In 69 patients on chronic haemodialysis, blood sampled randomly during dialysis was analyzed for carboxyhaemoglobin (COHb). The median value was 1.40% (range 0.9-2.3) in non-smoking patients and (1.4-7.5) in smokers. In non-smokers treated with erythropoietin (EPO) correlation was found between COHb and the weekly EPO dose (r = 0.57, p = 0.007). In smoking patients not given EPO, the COHb correlated well with the number of cigarettes smoked (r = 0.84, p = 0.003). The COHb values did not correlate to the haemoglobin values. It is concluded that COHb levels in uraemic non-smokers are elevated because of increased endogenous CO production from the enhanced erythrocyte turnover. As even low COHb levels may negatively influence the oxygen status of the uraemic patient, the addition of exogenous CO from cigarette smoking should be avoided.

Adult↗
PubMed1995

Continuous registration of blood oxygen tension during hemodialysis.

Continuous monitoring of blood oxygen tension was carried out during 45 hemodialyses sessions. The oxygen tension curves displayed different appearances. Some curves presented with a periodicity like sinus curves (type 1), while others (type 2) fluctuated with other appearances, or displayed straight lines. Blood pressure variations during dialysis were significantly greater during dialyses displaying type 1 curves than during those displaying type 2 curves (p values < 0.02). Due to a greater descend of S-urea during dialyses with type 1 curves than during dialyses with type 2 curves (p < 0.05) it is hypothesized, that the intensity of the dialysis treatment could be of some importance to the observed fluctuations in oxygen tension.

Adult↗
PubMed1995

Peritoneal equilibration test performed in predialysis patients.

The aim of the study was to perform peritoneal equilibration test (PET) in predialysis patients, and compared to PET results in patients on chronic peritoneal dialysis (PD). Two groups of patients were enrolled in the study. Group 1: eleven uremic patients who had never been subjected to PD, and group 2: fourteen patients on maintenance PD. The PET was performed as the four hour standard PET, using a 2 liter bag (Dianeal 2.5% glucose) as test fluid. The transport of creatinine through the peritoneum did not differ significantly between the groups corresponding to the dialysate to plasma (D/P) ratios, neither did the glucose ratios differ significantly. After two hours dwell time a significant difference was found in D/P ratio of urea (p = 0.001), in group 1 the median D/P of urea was 0.90 (0.80-1.14) and 0.75 (0.52-0.84) in group 2. No significant difference was found at dwell time zero or four hours. The current study shows that the distribution of PET results is identical in a group of predialysis patients, as compared to a group of chronic PD patients, except for D/P of urea at two hours dwell time.

Adult↗
PubMed1994

[Justification of routine autopsies after postoperative death].

Over a period from September 1981 to January 1983 data were collected from 97 autopsies following postoperative death (non-cardiac surgery). The autopsy rate was 73%. In 40% of the autopsies discrepancies were found between the clinical diagnosis and the cause of death found at autopsy. In 9% of the autopsies knowledge of the lesions that caused death might have changed the management of the patient and thus possibly also the prognosis. Since clinical practice has not changed considerably despite a ten year interval we consider the findings still valid today. Taking into account the decreasing rate of autopsy we want to stress that an important possibility of quality control of diagnosis and treatment in hospitals is about to be lost.

Adult↗
PubMed1994

p53 protein and c-erbB-2 protein (p185) expression in endometrial adenocarcinoma of endometrioid type. An immunohistochemical examination on paraffin sections.

The expression of both the nuclear protein p53 tumor suppressor gene product and the transmembrane C-erbB-2 protein oncogene product (p185) correlates to risk factors and outcomes in different tumor types. Their value as prognosticators in endometrial adenocarcinoma of endometrioid type (EC) has not been determined. Paraffin sections were examined immunohistochemically to study the expression of p53 protein and p185 in 112 patients with EC. p53 protein was overaccumulated in 34% and p185 in 13% of the tumors. p53 protein correlated with mitotic count and nuclear grade. Both p53 protein and p185 correlated significantly with outcome. However, they did not correlate with each other or with architectural grade or stage (which defines a high risk group), indicating a role as adjuvant prognosticators in EC. Stage and outcome did correlate, however. Both p53 protein and p185 antibodies work well on routine, formalin-fixed, paraffin-embedded tissue and are easily used in routine diagnostic procedures.

Aged↗