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Biomedical subjects

A Gabriel

Publications and source records attributed to A Gabriel.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Assessment of usefulness of PCNA and protein p53 in subjects with laryngeal cancer with local recurrence].

The authors estimated PCNA and P53 in subjects with laryngeal cancer in whom local or nodal recurrences were observed. The study included 54 patients from Upper Silesia in age 37-79 years (mean 57 +/- 8.8). The mean value of the PCNA index in subjects with local recurrence (LR) was 24.2% +/- 12.1 while in subjects without LR 22.1% +/- 9.4 (p > 0.05). Additionally, 21 subjects were separated from the investigated group in whom no lymph node metastases were found during laryngectomy. Among these subjects in 16 LR was observed (PCNA index was 30.9% +/- 12.5) while in remaining 5 subjects, in whom LR did not develop, PCNA index was 21.7% +/- 11.2. Analysis of the P53 index in subjects with LR revealed significantly higher values (19.2% +/- 9.1) in comparison to cases without LR (13.2% +/- 6.3). Our study revealed usefulness of the P53 and PCNA as markers which could support the histological diagnostic process describing biology of the cancer cells. The demonstrated increase of PCNA and P53 index in patients with LR might be useful in prediction of LR.

Adult↗
PubMed2000

[Precancerous states of the larynx: analysis of mono- and polyclonality of the cells with high proliferative index (p53, PCNA)].

The aim of the study was analysis of relationship between proliferation index (PCNA) and protein p53 content in dysplastic laryngeal epithelium and the degree of dysplasia, age of patients and smoking. The study population consisted of 45 patients (mean age 57.7 +/- 6.2) with chronic laryngitis. It was revealed epithelial dysplasia varying in intensity in 36 patients and epithelial hyperplasia without dysplasia (acanthosis) in 9 patients--control group. Mean value of p53 protein index was 8.91 +/- 7.43% in dysplastic epithelium and 3.67 +/- 3.4 in hyperplastic epithelium without dysplasia. The difference was statistically significant (p = 0.007). P53 content significantly differed between groups with grade I and grade II dysplasia (p = 0.03) and between groups with grade I and grade III dysplasia (p = 0.03). The difference was found between groups with grade II and III dysplasia and group with hyperplasia without dysplasia. The analysis of the correlation between degree of dysplasia and value of PCNA index showed absence of differences. There was no relationship between smoking, age of patients and Value of p53 and PCNA index.

Aged↗
PubMed2000

[The prospective analysis of laryngeal cancer growth dynamics in compliance with evaluation of DNA content and ploidy in cytologic material].

The aim of this study was evaluation of DNA ploidy in the cytological samples from patients with laryngeal cancer and comparison a type of DNA ploidy with histological grading (G) and staging of neoplasmatic process. The examinations were performed on 47 patients operated due to laryngeal cancer (3 women, 44 men, mean age 58). Cytological material was collected from squamous carcinoma tissue by imprinting method. Slides were staining by Feulgen method in order to quantitative analysis of DNA by static cytophotometry. In studied material, aneuploid, polyploid and hypoploid tumors were found in 22 patients and diploid tumors were found in 25 cases. Analysis of DNA ploidy type distribution in correlation to G feature showed:--diploid type were dominated in G1 and G2 tumors,--aneuploid and polyploid type were dominated in G3 tumors. Hypoploid and polyploid tumors were appeared in patients with metastases to cervical lymph nodes more frequently than in patients without metastases. Analysis of DNA ploidy complete traditional histopathological diagnosis of laryngeal cancer and may be useful in predicting metastases to cervical lymph nodes.

Cytological Techniques↗
PubMed2000

[Assessment of utility of nm 23 antigen as a metastatic potential marker in laryngeal cancers: preliminary study].

The aim of the study was the analysis of the utility of nm 23 protein in prediction of cervical lymph node metastases in patients with laryngeal cancer. A preliminary study was performed in 35 patients with laryngeal cancer with cervical lymph node metastases, which were confirmed by histopathologist. The control group consisted of 30 patients with laryngeal cancer without cervical lymph node metastases. In statistical analysis T and N were taken into account. In the investigated group with metastases the presence of positive immunostaining was found in 11% of cases while in the control group in 20%. The analysis of the presence of nm 23 protein revealed a weak usefulness of this marker as a factor which predicts the presence of the cervical metastases.

Antigens, Neoplasm↗
PubMed2000

[Assessment of usefulness of PCNA and oncoprotein p53 staining in prediction of the recurrences in subjects operated on for laryngeal carcinoma].

The authors estimated PCNA and P53 in subjects with laryngeal cancer with local or nodal recurrences. The study concerned 54 patients from Upper Silesia aged 37-79 (mean 57 +/- 8.8). The mean value of the PCNA index in subjects with local recurrence (LR) was 24.2% +/- 12.1 while in subjects without LR 22.1% +/- 9.4 (p > 0.05). Additionally, 21 subjects in whom no lymph node metastases were found during laryngectomy were separated from the investigated group. In 16 of them local recurrences were observed and the mean value of PCNA index was 30.9% +/- 12.5. In remaining 5 subjects in whom local recurrences were not developed the mean value of PCNA index was 21.7% +/- 11.2. The analysis of the P53 index in subjects with LR revealed significantly higher values (19.2% +/- 9.1) in comparison with cases without LR (13.2% +/- 6.3). The assessment of the mean values of PCNA and P53 index depending on T, N or stage as well as nodal recurrence did not reveal any statistical significance. Our study revealed usefulness of the P53 and PCNA as markers which could support the histological diagnostic process describing biology of the cancer cells. The demonstrated increase of PCNA and P53 index in patients with LR might be useful in prediction of LR.

Adult↗
PubMed1999

Absence of Brca2 causes genome instability by chromosome breakage and loss associated with centrosome amplification.

Women heterozygous for mutations in the breast-cancer susceptibility genes BRCA1 and BRCA2 have a highly elevated risk of developing breast cancer [1]. BRCA1 and BRCA2 encode large proteins with no sequence similarity to one another. Although involvement in DNA repair and transcription has been suggested, it is still not understood how loss of function of these genes leads to breast cancer [2]. Embryonic fibroblasts (MEFs) derived from mice homozygous for a hypomorphic mutation (Brca2(Tr2014)) within the 3' region of exon 11 in Brca2 [3], or a similar mutation (Brca2(Tr)) [4], proliferate poorly in culture and overexpress the tumour suppressor p53 and the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). These MEFs have intact p53-dependent DNA damage G(1)-S [3] [4] and G(2)-M checkpoints [4], but are impaired in DNA double-strand break repair [3] and develop chromosome aberrations [4]. Here, we report that Brca2(Tr2014/Tr2014) MEFs frequently develop micronuclei. These abnormal DNA-containing bodies were formed through both loss of acentric chromosome fragments and by chromosome missegregation, which resulted in aneuploidy. Absence of Brca2 also led to centrosome amplification, which we found associated with the formation of micronuclei. These data suggest a potential mechanism whereby loss of BRCA2 may, within subclones, drive the loss of cell-cycle regulation genes, enabling proliferation and tumourigenesis.

Aneuploidy↗
PubMed1999

Fidelity of retrotransposon replication.

Ty1, the genetically tractable retrotransposable element found in the yeast Saccharomyces cerevisiae, closely resembles vertebrate retroviruses both in structure and in mechanism of replication. By direct sequence analysis, we examined the rate and spectrum of new mutations appearing during a single cycle of Ty1 replication. The rate of new mutations was comparable to those seen for replicating retroviruses. All observed changes were base substitutions, and their location suggested that template ends may be hot spots for generating these mutations. To test this, we developed methods to examine, at the nucleotide level, the end structure of the expected Ty1 replication intermediates. Our results demonstrate that Ty1 reverse transcriptase can add terminal non-templated bases in vivo during each step in replication. Furthermore, Ty1 RNAse H creates multiple template ends by imprecisely cleaving RNA. This expands the range of sites of subsequent non-templated base addition. Finally, on reaching template ends, Ty1 reverse transcriptase can strand transfer to inappropriate templates. Taken together, these mutagenic mechanisms may influence the evolution of particular regions of the Ty1 genome and serve as a mechanism to regulate the overall level of Ty1 transposition in its host cell.

Animals↗
PubMed1999

Recurrent DNA copy number losses associated with metastasis of larynx carcinoma.

Squamous cell carcinomas of the head and neck show frequent and complex chromosome aberrations, but little is known about the changes that occur during the metastatic process. To compare the accumulation of changes in primary and metastatic tumors we analyzed 19 pairs of primary larynx cancer tumors and their metastases. The most frequent changes were found at 3p, 3q, 5p, 9, and 13. Losses at 13, 8p, and 9q were more frequent in metastases than in primary tumors.

Adult↗
PubMed1999

Upper posterior mediastinal tumor supplied by an atrial branch of the left circumflex artery.

We report a case of a 39-year-old woman with an upper posterior mediastinal tumor. The tumor was demonstrated by echocardiography and further defined by computerized tomography and magnetic resonance imaging. The tumor was fed by a large atrial branch of the left circumflex artery. Because of its location (adjacent to large vessels), it could not be resected by surgery.

Adult↗
PubMed1999

Clinical application of proliferating cell nuclear antigen, oncoprotein p53 and tumor front grading analysis in patients operated on for laryngeal cancer.

The authors assessed proliferating cell nuclear antigen (PCNA), p-53 oncoprotein and morphologic tumor front grading (TFG) in patients with advanced squamous cell carcinoma (SCC), of the larynx and a poor prognosis and tried to find a correlation with tumor stage, the Broders grading system, local and neck lymph node metastases, as well as nodal and local recurrences. In addition, utility of the parameters investigated was evaluated in developing a prognostic factor model, using uni- and multivariate Cox regression analysis. Included in this study were 54 patients (mean age 57 years +/- 8.6). PCNA-positive staining was found in all but one patient with advanced disease, while p-53 stained positively in only 24 subjects (44.4%). The PCNA index ranged from 4.6 to 59.0% (mean, 23.4 +/- 11. 0) and the p-53 index varied from 4.0 to 42.0% (mean, 17.2 +/- 8.6). The TFG score ranged from 9 to 23 points (mean, 15.1 +/- 3.2). PCNA, p-53 and TFG were found to be the markers that provided significant additional information about the biological behavior of tumor cells. The high variability of the results (PCNA, p-53) and high percentage of negatively stained cells (p-53) reduced their application in clinical use. PCNA correlated with tumor grade, G (r = 0.38; P < 0. 01), but negatively with nodal (N) disease(r = -0.37; P < 0.01). The mean values of PCNA and p-53 index were higher in the subgroup with local recurrences. Our present attempt to develop a useful prognostic factor model failed.

Adult↗
PubMed1999

Immunohistochemical analysis of lymphocytic infiltration in the tumor microenvironment in patients operated on for laryngeal cancer.

The aim of this study was to evaluate semiquantitative and qualitative analysis of lymphocytic infiltrations in a neoplasm microenvironment in patients with laryngeal cancers and the correlation analysis between the intensitivity degree and composition of lymphocytic infiltration in foreseeing a survival time and probability of the appearance of lymph node metastases. Postoperative specimens from 43 patients (Upper Silesia region) operated on for laryngeal cancer in the 2nd ENT Department, Silesian Medical University in Zabrze between 1985 and 1995 all had unfavorable courses due to tumor recurrences. The patients' ages ranged from 39 to 79 years (mean 57 years). Tissue specimens were subjected to routine processing. The degree of pathological changes was ascertained and immunohistochemical preparations of laryngeal tissue were prepared according to generally accepted methods. The following primary monoclonal antibodies were used: CD 3, CD 20, CD 43, CD 45 RO, CD 56. The distribution analysis of the intensity of the phenotype CD 43 evaluated the lymphocytic infiltration in relation to differentiation of the whole study group. The intensity of CD 43 cell infiltration increased in the group of patients with lymph node metastases. In patients with stage IV disease, a relationship was found between survival time and intensity of cell infiltrations with CD 43 and CD 45 RO lymphocytes. The influence of these two lymphocyte phenotypes in the patient subgroups - one after total laryngectomy with confirmed lymph node metastases and the other group without lymph node metastases - showed their prognostic value. Our analysis of lymphocytic infiltration, mostly of CD 43 cells, in the neoplasm microenvironment indicated a prognostic value for determining a shorter survival time and the possibility of lymph node metastases in patients with recurrences of cancer.

Adult↗
PubMed1999

Down-regulation of endothelin receptors by transforming growth factor beta1 in hepatic stellate cells.

BACKGROUND/AIMS: Hepatic endothelin-1 (ET-1) receptor density as well as the levels of both ET-1 and transforming growth factor beta1 (TGF-beta1) increase in liver cirrhosis. Considering their potent contractile (ET-1) and fibrogenic (TGF-beta1) actions on myofibroblastic stellate cells found in the fibrotic/cirrhotic liver, we aimed to investigate the effects of TGF-beta1 on ET-1 receptors and ET-1 synthesis in these cells. METHODS: Stellate cells isolated from rat liver by enzymatic digestion were cultured and subjected to TGF-beta1 treatment. Cellular ET-1 receptors and ET-1 released in the medium were determined. RESULTS: TGF-beta1 treatment produced time- and dose-dependent decrease in ET-1 binding sites, but did not affect the affinity of the receptors for ET-1. TGF-beta1 also stimulated the release of ET-1 from stellate cells. The extent of TGF-beta1-induced inhibition of [125I]ET-1 binding was much greater for ETB subtype (73+/-18% inhibition), which comprised a major portion (78+/-12%) of the total ET-1 receptors, than for ETA subtype (35+/-11% inhibition). The mRNA expression of the ET-1 receptors also was reduced by TGF-beta1 treatment. TGF-beta1-induced reduction in ET-1 receptor density was coupled to the inhibition of ET-1-stimulated release of [3Hlarachidonic acid from the prelabeled cells. The effects of TGF-beta1 were inhibited by a TGF-beta1 neutralizing monoclonal antibody. CONCLUSIONS: These results suggest that the TGF-beta1-induced decrease in ET-1 receptor density may be an important mechanism in limiting the pathologic actions of ET-1 on stellate cells in chronic liver disease.

Animals↗
PubMed1999

Patching broken chromosomes with extranuclear cellular DNA.

Chromosomal double-strand breaks (DSBs) can be repaired by either homology-dependent or homology-independent pathways. Using a novel intron-based genetic assay to identify rare homology-independent DNA rearrangements associated with repair of a chromosomal DSB in S. cerevisiae, we observed that approximately 20% of rearrangements involved endogenous DNA insertions at the break site. We have analyzed 37 inserts and find they fall into two distinct classes: Ty1 cDNA intermediates varying in length from 140 bp to 3.4 kb and short mitochondrial DNA fragments ranging in size from 33 bp to 219 bp. Several inserts consist of multiple noncontiguous mitochondrial DNA segments. These results demonstrate an ongoing mechanism for genome evolution through acquisition of organellar and mobile DNAs at DSB sites.

Base Sequence↗
PubMed1999

Detection of tryptase in bovine mast cells: comparison of enzyme- and immuno-histochemistry.

Mast cell (MC) phenotypes may vary with respect to tissue site, sensitivity to degranulating agents, dependency on T lymphocytes and, above all, the composition of their granules. Proteinases (either trypsin-like or chymotrypsin-like) are granule constituents which provide an important means of distinguishing subtypes of MCs in man and rodents. The purpose of this study was to compare the distribution of MC trypsin-like protease (tryptase) in a variety of bovine tissues with the aim of examining MC heterogeneity. Tryptase was found in MCs regardless of their location within tissues. With respect to tryptase content, bovine MC distribution resembled more that of human and canine tissues than that of mice and rats. Comparison of the results yielded by enzyme- and immuno-histochemical staining suggested that a tryptase-negative, dual-specific chymase-positive MC subset occurred, at least in duodenal lamina propria, around bronchioles and within alveolar septa. The study also suggested that monoclonal antibodies raised against human tryptase can be used for quantitation of bovine tryptase in biological fluids; this offers a promising tool for evaluating the role of MC activation in disease.

Animals↗
PubMed1998

Superoxide-induced changes in endothelin (ET) receptors in hepatic stellate cells.

BACKGROUND/AIMS: Reactive oxygen species are mediators of various pathophysiologic events, including postischemic reperfusion injury and inflammation. Generation of reactive oxygen species and consequent organ injury are associated with increased levels of a powerful vasoconstrictor peptide endothelin-1. Current evidence suggests that actions of endothelin-1 on the contractile and fibrogenic transdifferentiated stellate cells may play a critical role in hepatic pathophysiology. The aim of this investigation was to determine whether reactive oxygen species modulate the synthesis of endothelin-1 and its receptors in stellate cells. METHODS: Primary cultures of transdifferentiated stellate cells were exposed to reactive oxygen species-generating system, hypoxanthine/xanthine oxidase, before determination of endothelin-1 and its receptors. RESULTS: The treatment caused an initial decrease in ET-1 receptor density (about 30% at 30 min), followed by a significant increase over the basal level at 6 h. The increase in the receptors, which occurred specifically in the ET(B) subtype, progressed thereafter up to 24 h and was accompanied by an augmented functional response, as indicated by an enhanced endothelin-1-induced release of [3H]arachidonic acid from the prelabeled cells. Furthermore, treatment of cells for 24 h but not 30 min caused increased expression of ET(B) mRNA as determined by semi-quantitative polymerase chain reaction. The release of endothelin-1 in the culture medium was also enhanced by hypoxanthine/xanthine oxidase treatment. These effects of hypoxanthine/xanthine oxidase were inhibited by superoxide dismutase and dimethyl sulfoxide. ET-1-induced [3H]arachidonic acid release was also inhibited by the ET(B) receptor antagonist BQ788, but not by the ET(A) receptor antagonist BQ123. CONCLUSIONS: These findings indicate that interactions between ET-1 and stellate cells during episodes of the generation of reactive oxygen species can be an important mechanism in the pathophysiology of hepatic disorders.

Adipocytes↗