Biomedical subjects

R Kiss

Publications and source records attributed to R Kiss.

At least 181 records · Page 10Linked to original sources

PubMed1994

[Thyroid-stimulating hormone-secreting pituitary adenoma].

A 40-year-old male patient with a 2 years history of recurring hyperthyroidism is presented with clinical hyperthyroidism and diffuse goiter. Despite thyreostatic treatment and surgical thyroid ablation the hyperthyroidism recurred. The patient had laboratory evidence of hyperthyroidism and his serum TSH was persistently and enormously elevated (T4:214 nmol/l, T3:6.9 nmol/l, TSH:218 mIU/l)> Computed tomography and magnetic resonance imaging confirmed a pituitary mass of 7 cm in a-p diameter, with supra-, parasellar and sphenoidal extension. The pituitary adenoma was partially resected by transsphenoidal surgery, which failed to result in a substantial decrease in the serum thyrotropin level. Pituitary irradiation and a long-term somatostatin analog octreotide treatment (300-600 micrograms/die) combined with bromocriptine therapy resulted in a significant, but still incomplete suppression of thyrotropin secretion (TSH level about 15 mIU/l) and persisting mild hyperthyroidism. The size of the adenoma was unchanged during the two years of highdose octreotide treatment period. According to our best knowledge this is the first reported case of a thyrotropin-secreting pituitary adenoma in Hungary.

Adult↗

PubMed1994

Computer-assisted chromatin texture characterization of Feulgen-stained nuclei in a series of 331 transitional bladder cell carcinomas.

The chromatin patterns of Feulgen-stained nuclei in a series of six specimens of normal mucosa and 331 transitional bladder carcinomas, including 293 superficial (Ta and T1) and 38 invasive (T2-T4) cases, were quantitatively described by means of eight parameters relating to densitometric, run-length distribution, and co-occurrence matrix features. The results show that the chromatin texture of the superficial lesions was markedly different from that of the invasive tumours, which exhibited a distinctly more dense and heterogeneous chromatin pattern. The data also show that the increasing level of malignancy, as revealed by the increasing clinical stage, was accompanied by an increase in the overall chromatin condensation level. Only some areas of the nucleus actually increased in density; other pale areas appeared concomitantly with these increasingly denser chromatin areas. This chromatin density increase corresponded to a marked increase in the frequency of small dense chromatin clumps; these joined together into very large dense chromatin clumps, which were distributed more and more heterogeneously in the nucleus as the clinical stage of the tumour increased.

Adult↗

PubMed1994

Influence of culture media on the morphological differentiation of the PC-3 and DU145 prostatic neoplastic cell lines.

The concept of differentiation of prostate cancer in terms of morphonuclear characteristics and population dynamics was investigated on the PC-3 and DU145 cell lines. A software based on the concept of Voronoi paving was set up in order to characterize the structure of these cell lines growing in vitro on histological slides. The morphonuclear characteristics were assessed by means of the digital cell image analyses of Feulgen-stained nuclei. The in vitro "morphonuclear" and "pseudo-tissular" differentiations of the PC-3 and DU145 cells were described in terms of the use of various culture media, i.e., media supplemented with either 10% (F10 medium) or 1% (F1 medium) fetal calf serum and with (or without) platelet-derived growth factor and dihydrotestosterone (PA10 and PA1 media). The present data reveal that the PC-3 cell line would be more hormone-sensitive than the DU145 one. Indeed, decreasing the FCS concentration in the culture medium while adding DHT and PDGF led to marked modifications to the morphonuclear characteristics of the PC-3 cells, but not to the DU145 cells. These modifications corresponded to an increase in nuclear size occurring concomitantly with chromatin decondensation. In the same way, spectacular modifications in terms of medium-induced pseudo-tissular differentiation were observed in the PC-3 cell line, but not in the DU145 one. Such modifications corresponded to an increase in clone size related to an increase in the mean distances between neighboring cell nuclei in a given clone. Thus, according to the criteria defined in this study, the PC-3 cell line would seem to maintain a higher degree of differentiation than the DU145 cell line.

Animals↗

PubMed1994

Characterization of the influence of anti-hormone and/or anti-growth factor neutralizing antibodies on cell clone architecture and the growth of human neoplastic astrocytic cell lines.

The influence of five anti-hormone and/or anti-growth factor neutralizing antibodies on the in vitro proliferation of four human astrocytic tumor cell lines (U87, U138, U373, H4) is quantitatively described by means of a new tool which makes it possible to evaluate cell growth and cell clone architecture concomitantly. This tool relies upon the combined use of the digital cell image analyses of Feulgen-stained nuclei and the Delaunay and Voronoi mathematical triangulation and paving techniques. Of the five anti-hormone and/or anti-growth factors tested here, the anti-luteinizing hormone-releasing hormone (LHRH) antibody induced the most marked perturbation in the U138 and U373 cell lines, whereas this role was played by the anti-epidermal growth factor (EGF) antibody in the U87 and H4 cell lines. The anti-gastrin (G) antibody significantly modified the growth and/or cell clone architecture of the U138, U87 and H4 cell lines, as did the anti-transforming growth factor alpha (TGFalpha) antibody. The anti-transforming growth factor beta (TGFbeta) antibody modified the growth and/or cell clone architecture of the four cell lines under study. If the five antibodies are taken into consideration, the results strongly suggest that four (the anti-G, the anti-EGF, the anti-LHRH and the anti-TGFalpha) act as inhibitory agents on some glioma cell line proliferation, while the fifth one, i.e. the anti-TGFbeta, act as a stimulator of cell proliferation, perhaps by abrogating the inhibitory effects of TGFbeta on proliferation. A comparison of cell growth data with cell clone architecture characteristics provided further evidence of some specific influence exercised by a given hormone and/or growth factor on glioma cell proliferation. Indeed, the anti-LHRH antibody caused the most pronounced perturbations in the U138 and U373 cell clone architecture; this feature was observed in the H4 cell line and, to a lesser extent in the U87 one after the anti-EGF antibody had been used.

Antibodies, Monoclonal↗

PubMed1994

Determination of DNA ploidy, nuclear size, and proliferative activity by means of the computer-assisted image analysis of Feulgen-stained nuclei in 68 soft tissue tumors of adults.

The diagnostic values of the ploidy level, the proliferative activity, and the nuclear size in a series of 68 soft tissue tumors of adults were determined by digital cell image analysis of Feulgen-stained nuclei from formalin-fixed, paraffin-embedded tissues. The DNA ploidy level was characterized by calculating the DNA index (DI) and the percentage of the diploid and polyploid cells, and by typing the DNA histogram. Proliferative activity assessments were a function of the determination of the proliferation index (PI), ie, the percentage of cells engaged in the S phase of the cell cycle (SPF value). The present series included 19 benign and 49 malignant soft tissue tumors. The results show that DNA aneuploidy, as assessed by both the DI and the DNA histogram type, cannot be used as a discriminatory parameter for distinguishing between benign and malignant soft tissue tumors. Indeed, some benign cases may be highly aneuploid, whereas some highly malignant soft tissue tumors may be definitely diploid. In contrast, the determination of the percentage of polyploid cell nuclei seems to be a useful parameter in distinguishing between benign and malignant cases. In fact, the benign soft tissue tumors showed a very significantly lower mean percentage value of polyploid cell nuclei than the malignant cases. The determination of the proliferative activity also discriminated significantly between the benign and the malignant cases, the former proliferating more slowly than the latter. Lastly, the determination of nuclear size made it possible to differentiate the primary malignant soft tissue tumors, whether recurrent or not, that were associated with metastasis from those free of metastasis.

Adult↗

PubMed1994

Computer-assisted quantitative description of chromatin pattern in soft tissue tumors of the adult.

The chromatin pattern in Feulgen-stained nuclei from soft tissue tumors was quantitatively described by means of computer-assisted microscope analysis. The morphonuclear parameters described densitometric, run length, and co-occurrence matrix features. The present series of cases, which relied upon archival (ie, formalin-fixed, paraffin-embedded), tissues, included 19 benign (9 lipomas and 10 leiomyomas) cases, and 49 malignant (31 primitive non-recurrent, 14 primitive locally recurrent, and 4 metastatic) cases. The 31 primitive nonrecurrent cases included 12 liposarcomas, 11 leiomyosarcomas, 4 rhabdomyosarcomas, and 4 malignant fibrohistiocytomas. The results show that the quantitative description of chromatin patterns in Feulgen-stained nuclei made it possible to distinguish between certain benign and malignant soft tissue tumors. However, this was true only when specific histopathologic groups were taken into consideration. Indeed, the lipomas were markedly different from the liposarcomas, whereas the leiomyomas closely resembled the leiomyosarcomas. The quantitative description of the chromatin patterns also made it possible to identify certain clinically aggressive soft tissue tumors. In this context, the authors observed that the chromatin pattern in the cell nuclei from the group of patients whose tumors had recurred less than 10 months after first surgery was significantly more heterogeneous and less condensed than in the cell nuclei from patients whose tumors had recurred more than 10 months after this surgery. In the same manner, the morphonuclear parameters under study made it possible to establish a more marked distinction between the primitive and recurrent soft tissue tumors that developed a metastasis between 3 and 48 months after the diagnosis, and those tumors free of metastasis until 38 months after the diagnosis. The former group exhibited cell nuclei with a chromatin pattern markedly more condensed and heterogeneous than in the case of the cell nuclei belonging to the latter group.

Adult↗

PubMed1994

Computer-assisted microscope analysis of morphonuclear modifications induced by anticancer antimetabolites in cell lines cultured in vitro.

An original method is proposed for the purpose of discriminating between antimetabolites exhibiting different operating mechanisms. The present work was carried out by means of the digital cell image analysis of Feulgen-stained nuclei cultured in the presence of different antimetabolites. We chose this method because it enables anticancer drug-induced effects to be studied at both morphonuclear and cell cycle levels in the same biological sample. The results show that all the antimetabolites had similar effects on the nuclear texture of the cells and on cell cycle parameters. Furthermore, the use of multivariate analyses made it possible to distinguish between different mechanisms of action among drugs belonging to the same class of antineoplastic, i.e. antimetabolite agents.

Animals↗

PubMed1994

Prognostic scoring in adult astrocytic tumors using patient age, histopathological grade, and DNA histogram type.

High-grade astrocytic tumors constitute the most serious as well as the most common group of primary brain tumors. Although several prognostic factors have been proposed, little is known about the prognostic value of deoxyribonucleic acid (DNA) ploidy in adult astrocytic tumors. In a series of 146 adult patients, aged 16 to 82 years, the individual prognostic values of six variables were studied, namely: tumor histopathological grade, treatment, patient age, extent of tumor, ploidy level, and DNA histogram type. Cox's proportional hazard model was then applied to the data to ascertain which factors might independently determine patient survival. Univariate analyses revealed that histopathological grade, age, and DNA histogram type were very powerful prognostic factors. The statistical significance of the influence of adjuvant radiotherapy and chemotherapy was at a borderline level, and the two remaining variables (tumor extent and ploidy level) had no prognostic relevance. Multivariate analyses showed that age, histopathological grade, and DNA histogram type were independent, statistically significant prognostic factors. A prognostic score was calculated from Cox's polynomial function in which those factors were introduced. The best score corresponded to a patient aged 16 years with a hypertriploid low-grade astrocytoma, while the worst score corresponded to a patient aged 82 years with a diploid high-grade astrocytoma. The worst score:best score ratio revealed a risk 71 times higher for a bad prognosis. It is concluded that patient age, histopathological grade, and DNA histogram type are very powerful prognostic factors for adult astrocytic tumors. A prognostic score including those factors could be used to characterize astrocytic tumor aggressiveness presurgically on fine-needle aspirates, and to monitor the patient's postsurgical evolution to define the appropriate therapy.

Adolescent↗

PubMed1994

The use of digital cell image analysis of Feulgen-stained nuclei to quantitatively describe morphonuclear features in a series of 174 meningiomas.

The morphonuclear characteristics of 174 meningiomas were quantitatively described by means of the digital cell image analyses of Feulgen-stained nuclei. For this purpose, archival material, i.e., formalin-fixed paraffin-embedded pronase-digested tumors, was used. The present work specifically focuses on the morphonuclear features of angioblastic meningiomas to localize them with respect to classical as opposed to malignant meningiomas. The results show that angioblastic meningiomas, i.e., hemangioblastomas, have morphonuclear characteristics that are very similar to those of classical meningiomas, i.e., meningotheliomatous, fibroblastic, transitional, angiomatous, and psammomatous types, and that are significantly distinct from those of malignant meningiomas. Malignant meningiomas, i.e., the hemangiopericytic and histologic features of malignancy types, are not only significantly different from classical meningiomas in their morphonuclear characteristics but are also very different among themselves. In conclusion, the quantitative description of chromatin features by means of digital cell image analyses confirms at the morphonuclear level the adherence of hemangioblastomas to the group of classical meningiomas, as suggested by the World Health Organization's histopathologic classification.

Cell Nucleus↗

PubMed1994

Computerized morphonuclear analyses of Feulgen-stained nuclei from 11 chemosensitive and from 11 chemoresistant neoplastic cell lines.

It has previously been demonstrated that the cell nuclei from 1 mouse mammary cancer and 2 neoplastic human bladder cell lines displayed common morphonuclear characteristics when they were made resistant to different anti-neoplastic agents. In the present work this experiment was repeated with a greater number of cell lines from different kinds of tumours. The nuclei from the sensitive and resistant cells were submitted to Feulgen staining and studied by means of computerized nuclear image analysis. This methodology made it possible to characterize the cell nuclei by means of 15 parameters including 1 geometric, 2 densitometric and 12 others quantitatively describing the chromatin pattern. The results showed that the morphonuclear feature of the cell lines significantly varied according to the extent of the resistance. The majority of the observations showed that the direction of the variations seemed to be a function of the origin of the tissue. On the basis of the experimental results reported here, we think that it would be possible to establish a model for the purpose of monitoring the effectiveness of anticancer treatment from a clinical point of view.

Animals↗

PubMed1993

In vitro characterization of radiotherapy-induced morphonuclear modifications on chemosensitive as opposed to chemoresistant neoplastic cells.

PURPOSE: We describe by means of digital cell image analysis the influence of X-ray radiation on three in vitro cultured cell lines for which we set up chemosensitive and chemoresistant variants. METHODS AND MATERIALS: The three cell lines correspond to the MXT mouse mammary and the T24 and J82 neoplastic human bladder cells. The digital cell image analysis was carried out by computing morphometric (nuclear size), densitometric (proportion of cells in the G2 cell cycle phase), and textural features (chromatin pattern characteristics) on Feulgen-stained nuclei. RESULTS: The results show that such digital cell image analyses make it possible to monitor radiotherapy-induced effects on these morphonuclear characteristics accurately. X-ray radiotherapy induces a dose-dependent increase in the proportion of cells in the G2 phase of the cell cycle along with a decrease in the overall chromatin condensation level. These two concomitant phenomena lead to a marked radiotherapy-induced increase in nuclear size. We also observed that radiotherapy-induced effects at the morphonuclear level are not only highly specific to the cell type analyzed, that is MXT mouse mammary or J82 or T24 human bladder carcinoma cells, but also to the fact that the cells are either chemosensitive or chemoresistant. CONCLUSION: The digital cell image analyses of Feulgen-stained nuclei is helpful in monitoring the irradiation-induced morphonuclear modifications.

Animals↗

PubMed1993

[Flow-cytometric study of the DNA content in adrenal cortex tumors].

Flow cytometric deoxyribonucleic acid measurements were performed on 26 adrenocortical tumours and 9 non-tumours adrenals. All but one tumours were classified both histologically and clinically as benign, however, two thirds of them had abnormal deoxyribonucleic acid stemlines. Proliferative indices of adenomatous tissues were significantly higher than those of non-tumorous adrenals (p < 0.01). When compared to tumors smaller than 5 cm in size, tumours larger than 5 cm displayed significantly higher proliferative indices (p < 0.01). Thus, flow cytometry appears to have only a limited value in distinguishing between benign and malignant adrenocortical tumours, but it may provide additional information about the prognosis of these tumours.

Adenoma↗

PubMed1993

Characterization of the differentiation of human colorectal cancer cell lines by means of Voronoi diagrams.

This paper describes differentiation in terms of population dynamics through the medium of Voronoi paving which enables (via digital cell image analysis) the structure of human LOVO and HCT-15 colorectal neoplastic cell colonies growing on histological slides to be characterized. Two other tests were also used, i.e., the colorimetric MTT assay that enables the cell growth level to be determined, and a test allowing the assessment of the proliferation index, i.e., the percentage of cells in the S phase of the cell cycle. The results show that these colorectal neoplastic cells exhibited a comparatively high level of organisation in terms of the topographical distribution of nuclei within the clones when the cells were cultivated in media containing even small amounts of fetal calf serum. On the other hand, certain chemically defined media completely overturned this "pseudo-tissular" architecture. Furthermore, the colorectal cells growing in media including fetal calf serum exhibited relatively large and dense clones, undergoing an increase in the density of these clones when hormones were added to the culture medium and, concomitantly, a decrease in their proliferation. In contrast, the cells growing in chemically defined media generally exhibited smaller clones whose cell proliferation was paradoxically greater than that of the cells referred to above. This seems to bring out the importance of the part played by the cell loss factor in this cell population dynamic.

Adenocarcinoma↗

PubMed1993

Digital cell image analysis of verapamil-induced effects in chemosensitive and chemoresistant neoplastic cell lines.

We used chemosensitive and chemoresistant variants of the neoplastic mouse MXT mammary and human J82 and T24 bladder cell lines to characterize verapamil-induced cell proliferation and morphonuclear modifications in drug-treated and untreated cells. Chemoresistance to vinorelbine (Navelbine, a Vinca alkaloid derivative), to DIAM3 (an investigational alkylating compound) and to Adriamycin (an intercalating agent) in the presence or absence of verapamil was monitored by means of the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The results showed that verapamil restored a significant level of chemosensitivity in doses such as 1 microM or 10 microM in the three chemoresistant variants. The digital cell image analysis of Feulgen-stained T24-resistant cell nuclei revealed that verapamil restored the drug-treated cell kinetics and morphonuclear features observed in the sensitive counterpart especially with respect to the effects of Adriamycin. Interestingly, verapamil induced a highly significant chromatin decondensation in resistant but not in sensitive variants. Such verapamil-induced decondensation may favour the accessibility of drugs to their DNA targets. Therefore, in addition to the well-known action of the drug on the influx of a cytotoxic compound from the cellular to the intracellular compartment, verapamil might also favour the accessibility of the nucleus, to the drug.

Analysis of Variance↗

PubMed1993

Monitoring of chemotherapy-induced morphonuclear modifications by means of digital cell-image analysis.

We illustrate the potential application of digital cell-image analysis to characterize the morphonuclear modifications induced by various drugs including VP16, a podophyllotoxin derivative, PE1001, an investigational alkylating agent, and doxorubicin, an intercalating agent. Fifteen parameters representative of morphometric (nuclear area), densitometric (nuclear DNA content), and textural (chromatin organization, condensation, and distribution) features were computed on Feulgen-stained nuclei obtained from fine-needle aspirations serially performed during treatment on the MXT mouse mammary cancer model. We observed marked differences between the control and drug-treated MXT cell nuclei. However, mathematical data processing was necessary to improve the ratio of the chemotherapy-induced morphonuclear signal to the control biological morphonuclear signal. This data processing relies upon the use of principal-component analysis followed by the canonical transformation of data. The present method can be applied to all human cancers on which fine-needle aspiration can be performed.

Animals↗

PubMed1993

Direct inhibitory effect of etomidate on corticosteroid secretion in human pathologic adrenocortical cells.

Etomidate has been shown to inhibit corticosteroid secretion in the normal adrenal gland, but its direct effect in human pathologic adrenals has not been clearly established. In the present study the effect of varying doses of etomidate (10(-11)-10(-5) M) was investigated on basal and adrenocorticotrophic hormone (ACTH)-stimulated corticosteroid secretions in isolated adrenocortical cells obtained from two patients with primary aldosteronism (adenoma and micronodular hyperplasia) and in those from a patient with Cushing's syndrome (adenoma). In cells from primary aldosteronism, increasing concentrations of etomidate (10(-11)-10(-5) M) produced a dose-dependent decrease of basal and ACTH-stimulated cortisol, aldosterone, 18-hydroxycorticosterone, and corticosterone secretions (ED50: 10(-9)-10(-8) M for each of these corticosteroids). In the same cells, the secretions of 11-deoxycortisol and deoxycorticosterone were increased in the presence of low (10(-9)-10(-7) M) but not high doses of etomidate (10(-6)-10(-5) M). In cells from Cushing's syndrome the changes in corticosteroid secretion were similar to those found in primary aldosteronism except that aldosterone and 18-hydroxycorticosterone could not be determined due to their low levels. Thus the potent inhibition of corticosteroids in human pathologic adrenocortical cells in the presence of low concentrations of etomidate may be predominantly due to inhibition of the 11 beta-hydroxylase enzyme, whereas higher doses of the drug may inhibit earlier steps of the corticosteroid biosynthetic pathway.

18-Hydroxycorticosterone↗

PubMed1993

Relationship between proliferative activity and ploidy level in a series of 530 human brain tumors, including astrocytomas, meningiomas, schwannomas, and metastases.

By identifying six DNA histogram types (diploid, hyperdiploid, triploid, hypertriploid, tetraploid, and polymorphic) in a series of 206 astrocytic tumors, we showed recently that patients with hypertriploid astrocytic tumors have a better possibility of survival than patients with other DNA histogram-type related tumors. In the present work DNA histogram type and proliferation index (S-phase fraction) are characterized in a series of 530 adult tumors from the central and peripheral nervous systems. Of these 530 tumors, there were 79 nerve sheath tumors, 181 meningiomas, 221 astrocytic tumors, and 49 metastases. Analysis was performed by means of digital cell image examination of Feulgen-stained nuclei from formalin-fixed, paraffin-embedded tumors. The data reveal that there was a majority of diploid tumors (66%) in the primary tumor group (nerve sheath tumors, meningiomas, and astrocytic tumors), while aneuploid tumors were in a marked majority (90%) in the secondary (metastatic) brain tumor group, with a predominance (47%) of the polymorphic tumor type. Independently of tumor histopathologic group, the hypertriploid-type tumors proliferated less actively than the five other types. Such a feature might partly explain the better prognosis associated with hypertriploid astrocytic tumors as compared with what occurs with respect to the other DNA histogram-type related tumors.

Astrocytoma↗

PubMed1993

Ploidy level and proliferative activity measurements in a series of 407 thyroid tumors or other pathologic conditions.

This study describes the ploidy level and proliferation rate in a series of 74 multinodular goiters (MNGs), 17 cases of Hashimoto's disease, 33 cases of Basedow's disease, 113 adenomas, 139 primary carcinomas, and 31 cervical lymph node metastases from 376 patients. Both ploidy level and proliferation rate were assessed by digital cell image analyses of Feulgen-stained nuclei from formalin-fixed, paraffin-embedded tissues. The ploidy level of each sample was assessed using both its DNA index and its DNA histogram type. The proliferation index assessments corresponded to the determination of the proportion of cells in the S-phase fraction. The data reveal that the proportion of aneuploid cases increases according to the following sequence: simple MNGs and normomacrovesicular adenomas-->MNGs with adenomatous hyperplasia and microvesicular adenomas and Hürthle cell adenomas-->papillary and Hürthle cell carcinomas-->follicular and medullary carcinomas-->anaplastic carcinomas. This suggests the preneoplastic nature of the microvesicular adenomas and even of MNGs with adenomatous hyperplasia. The ploidy levels of 99% of the 407 cases of the thyroid tumor series could be described using six DNA histogram types: diploid, hyperdiploid, triploid, hypertriploid, tetraploid, and polymorphic. It was possible to assess the proliferation rate of 279 samples. The results show that a significantly higher proportion of malignant compared with benign thyroid tumors (35.5% v 10.5%, respectively) exhibited a proliferation index higher than 5%, and that, whether benign or malignant, the hypertriploid thyroid tumors proliferated significantly less than the nonhypertriploid thyroid tumors.

Cell Division↗