Biomedical subjects

R Kiss

Publications and source records attributed to R Kiss.

At least 217 records · Page 12Linked to original sources

PubMed1992

Relationship between histopathologic typing and morphonuclear assessments of 238 thyroid lesions. Digital cell image analysis performed on Feulgen-stained nuclei from formalin-fixed, paraffin-embedded materials.

A digital cell image processor was used to compute 15 parameters on Feulgen-stained thyroid nuclei from 238 archival, i.e., formalin-fixed, paraffin-embedded thyroid lesions. The morphonuclear parameters were related to morphometric (nuclear area), densitometric (nuclear DNA content), and textural (chromatin pattern characteristics) features. With respect to development of a malignant condition, their variations were compared with the World Health Organization's International Histological Classification of thyroid tumors. The relationship between morphonuclear parameter assessments and tumor size and the presence or absence of metastasis at the time of diagnosis was also investigated: no relationship with respect to cytomorphonuclear assessments was found. Nuclear area and nuclear DNA content discriminated between simple multinodular goiters and multinodular goiters with adenomatous hyperplasia. In the same way, the mean parameter values describing the chromatin pattern of multinodular goiters were significantly distinct from those describing the chromatin pattern of adenomas and carcinomas. Furthermore, chromatin pattern descriptions made it possible to discriminate between cell nuclei from papillary carcinomas and follicular carcinomas, and further between follicular carcinomas and follicular adenomas. A marked variation was observed within individual cases of multinodular goiters, adenomas, and carcinomas, a feature suggesting that morphonuclear assessment is of limited value for the diagnosis of individual clinical cases. In contrast, these results show that morphometric, densitometric, and textural nuclear assessments are useful aids for thyroid tumor typing, adding interesting results with respect to thyroid tumor progression. Indeed, the primary findings demonstrate that nodules with adenomatous hyperplasia from multinodular goiter lesions and microvesicular adenomas more closely resemble follicular carcinomas than do simple multinodular goiters and normomacrovesicular adenomas. Such data might reflect a biologic progression from benign to malignant follicular thyroid lesions.

Adenoma↗

PubMed1992

Modification of tumor ploidy level via the choice of tissue taken as diploid reference in the digital cell image analysis of Feulgen-stained nuclei.

We studied the influence of five cell nucleus populations taken as diploid standards with respect to the normalization of a human breast carcinoma. Four normal human tissues (lymphocytes, thyroid, liver, and bladder specimens) were taken as external standards, while the normal breast cells "contaminating" the tumor were taken as the internal diploid standard. Nuclear size and nuclear DNA assessments were performed by means of a cell image processor computing the parameters on Feulgen-stained nuclei from fresh imprint smears fixed in an ethanol-formalin-acetic acid mixture. Our results demonstrate that the choice of normal tissue as the diploid standard markedly influences the ploidy level of breast carcinoma. Normalization according to the lymphocytes led to our obtaining a major hyposextaploid G0-G1 DNA peak in the breast cancer. Using thyroid and liver cells as a standard, we obtained a major pentaploid and sextaploid G0-G1 peak, respectively. Using bladder cells or the normal contaminating breast cells within the tumor, we obtained a major tetraploid G0-G1 peak. Finally, the normalization of the normal bladder cells against the liver cells led to our obtaining a near triploid bladder specimen. The reverse feature was also observed, e.g., the obtaining of biologically nonsensical hypodiploid liver cells after normalization against the normal bladder cells. Such postnormalization variations in ploidy level depend upon the mean nuclear size and the mean nuclear DNA content of the normal tissue taken as diploid standard.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

PubMed1992

Comparison of morphonuclear features in normal, benign and neoplastic thyroid tissue by digital cell image analysis.

We analyzed the morphonuclear features of thyroid cell nuclei from 10 normal tissues (10 multinodular goiters), 10 benign tissues (10 adenomas) and 10 neoplastic tissues (10 carcinomas--2 follicular, 2 medullary and 6 papillary). These morphonuclear features quantitatively described the nuclear size, DNA content and chromatin texture of 200-400 Feulgen-stained cell nuclei that were digitized by means of a cell image processor. Nuclear DNA estimations revealed that the benign thyroid tumors showed an aneuploidy level that was not different from that of the neoplastic tissues. Morphometric measurements showed a significant and positive correlation between an increase in nuclear area and the development of thyroid pathology--i.e., from normal to a neoplastic stage. We also observed a significant decrease in chromatin condensation and heterogeneity from normal to neoplastic thyroid tissue. In the specific case of thyroid tumors, such criteria were not found sufficient per se for a diagnosis of malignancy. More detailed data banks will be necessary for this purpose.

Adenocarcinoma↗

PubMed1991

Digital morphonuclear analyses of sensitive versus resistant neoplastic cells to vinca-alkaloid, alkylating, and intercalating drugs.

We tested 12 resistant cell lines in vitro in order to evaluate common morphonuclear characteristics induced by various cytotoxic drugs on cell lines of different origins. We used the MXT mouse mammary cancer and the neoplastic J82 and T24 human bladder cell lines, whose variants are either sensitive or resistant to a vinca alkaloid derivative (Navelbine, NVB), to an investigational alkylating agent (PE1001), and to Adriamycin (ADR). We tested cell population variants resistant to NVB + PE1001 + ADR. The level of chemoresistance was evaluated by a colorimetric assay assessing the 50% concentration-induced inhibition of cellular growth (IC50) brought about by each drug on the growth of each cell variant under study. We show that resistant neoplastic cell nuclei present common morphonuclear characteristics, independent of cell origin (neoplastic mouse mammary versus human bladder cells) and the drug used (vinca alkaloid, alkylating, and intercalating derivatives). Our results further indicate that the phenotype of resistant versus sensitive cells corresponds to cell nuclei populations with smaller nuclei and less nuclear DNA content and, as a consequence, a chromatin texture showing large pale areas with some hyperchromatic clumps.

Alkylating Agents↗

PubMed1991

Influence of fetal bovine serum and hormones on primary vs. long-term cultures of human breast cancers.

We investigated the influence of fetal bovine serum, complemented or otherwise with estradiol or insulin or both, on the proliferation of mammary cancer cells from long-term and primary cultures. The long-term culture corresponded to mouse MXT and MCF-7 cell lines whereas the primary culture corresponded to primitive breast cancers squashed onto histologic slides and maintained in cultures for between 12 and 48 h. Cell proliferation was evaluated by means of digital cell image analysis of Feulgen-stained nuclei. Our results show that the addition of estradiol and insulin slightly but nevertheless significantly increases the proportion of cells still living at Hour 48 of culture. Fetal bovine serum, necessary for the growth of MXT and MCF-7 mammary cells, was highly cytotoxic with respect to the primary cultures of the 20 breast cancers under study. We are now conducting new experiments using chemically defined media to study the influence of new antineoplastic compounds on primary cultures of breast cancers.

Animals↗

PubMed1991

Quantitative nuclear cell image analyses of thyroid tumors from archival material.

Sixty-three sections of Feulgen-stained thyroid cell nuclei from paraffin-embedded material, including five multinodular goiters, 10 adenomas, 36 papillary carcinomas, seven follicular carcinomas, and five medullary carcinomas were analyzed by means of the SAMBA 200 (TITN, Grenoble, France) cell image processor. This was done in order to obtain nuclear characteristics of papillary versus follicular carcinomas. The nuclear features were assessed by morphometric, densitometric, and textural parameters. Our preliminary results indicate that the cell nuclei from typical histopathologic specimens of follicular thyroid cancers belong to a larger thyroid cell nuclei population corresponding to the histopathologic family of papillary thyroid cancers. This follicular neoplastic cell nuclei population appears to be quite distinct from the typical medullary neoplastic cell nuclei population which also belongs to the papillary neoplastic cell nuclei population. It appears that there is a specific papillary cell nuclei subpopulation containing typical hypochromatic cell nuclei. We also observed a dramatic increase in nuclear size and hyperchromatism between normal (multinodular goiters) and neoplastic (carcinomas) thyroid tissues, with the benign tissues (adenomas) showing intermediate nuclear characteristics.

Adenocarcinoma↗

PubMed1991

In vitro influence of gastrin, oestradiol and gonadotropin-releasing hormone on HCT-15 and LoVo human colorectal neoplastic cell proliferation.

We set up in vitro several human colorectal neoplastic cell lines that we labelled "hormone-sensitive" (HS) in comparison to the original cell lines which appeared to be rather "hormone-insensitive" (HI). We used LoVo and HCT-15 human colorectal neoplastic cell lines and studied the influence of 17 beta-oestradiol (E2), gastrin and two gonadotropin-releasing hormone (GnRH) analogues, HRF and buserelin, on the proliferation of the HS and HI variants of the LoVo and HCT-15 cell lines. Cell proliferation was evaluated by a colorimetric assay, the MTT test. Our results show that E2, gastrin, HRF and buserelin did not induce a significant stimulatory influence on the HI variants of the LoVo and HCT-15 cells, i.e. the cells that were cultured in a hormone-free 10% FCS-supplemented medium. In sharp contrast, the colorectal cells cultured for 30 passages in an E2 and/or gastrin + 1% FCS-supplemented medium showed a marked tropic response to E2, gastrin, HRF and buserelin. However, the HS variants of the HCT-15 cells appeared less sensitive to the two GnRH analogues than did the HS variants of the LoVo cells.

Cell Count↗

PubMed1991

Morphonuclear relationship between prostatic intraepithelial neoplasia and cancers as assessed by digital cell image analysis.

Using digital cell image analysis performed on Feulgen-stained nuclei, the nuclear characteristics of prostatic neoplasia, ranging from benign (benign prostatic hyperplasia [BPH]), through dysplastic (prostatic intraepithelial neoplasia [PIN] 1-3), to carcinoma were studied. Four histopathologic groups were studied: group IA (18 samples) contained BPH, PIN 1, and PIN 2 lesions that were from 9 prostate samples free of cancer. Group IB (23 samples) was identical to group IA, contained also BPH, PIN 1, and PIN 2 lesions, but lesions that were from 7 prostate samples where malignant foci were detected elsewhere. Group II (11 samples) were PIN 3 specimens. Group III (24 samples) were carcinomas. Features of neoplastic nuclei were quantified objectively through morphometric (nuclear size), densitometric (nuclear DNA content), and textural (chromatin organization and heterogeneity) parameters. Cell kinetic parameter, i.e., cell proliferation index, was assessed from the densitometric measurement. The proliferation index was significantly higher in PIN 3 and cancers as compared to BPH, PIN 1, and PIN 2 tissues. Morphonuclear characteristics were also dramatically distinct among the four groups. Indeed, the nuclear size and the hyperchromatism of severe prostatic dysplasia were similar to those of carcinomas, these two lesion types showing mean parameter values that were higher as compared to BPH, PIN 1, and PIN 2 lesions. Finally, benign tissues related to mild or moderate dysplasia taken in histologic material in which cancer was present already share the morphonuclear characteristics of severe dysplasia, although they are nonproliferating.

Cell Nucleus↗

PubMed1991

Use of computerized cell image analysis to characterize cell nucleus populations from normal and neoplastic renal tissues.

We studied 55 renal tissue samples from 16 patients corresponding to normal (19 samples, group 1), low-grade (18 samples, group 2), and high-grade (18 samples, group 3) tumoral tissues. For this purpose, we used digital cell image analysis (the SAMBA 200 processor) to describe the morphonuclear patterns of Feulgen-stained nuclei from the 3 above-mentioned groups. Our results show that nuclear DNA ploidy is positively correlated with histopathological differentiation, which is also positively correlated with an increase in nuclear DNA heterogeneity. Morphometric and textural parameters computed on such Feulgen-stained nuclei make it possible to describe the typical morphonuclear patterns of normal, low-grade, and high-grade neoplastic renal tissues. Using multiparametric, i.e. principal-component and canonical analyses, we set up preliminary morphonuclear data banks that we used to assess the diagnosis of 6 ungraded samples. We expect that this kind of morphonuclear data banks might be helpful, on one hand, to select specific morphonuclear parameters related to patient survival, and on the other hand to establish the cytological diagnosis of deep fine-needle aspiration material, sonographically assisted, on suspicious kidneys. Such hypotheses are now under further study.

Aged↗

PubMed1991

Dissociation of plasma atrial natriuretic peptide responses to upright posture and furosemide administration in patients with normal-, low renin essential hypertension and primary aldosteronism.

Plasma levels of atrial natriuretic peptide (ANP) were measured in patients with normal renin essential hypertension (n = 12), low renin essential hypertension (n = 11) and primary aldosteronism due to aldosterone producing adenoma (APA, n = 8) and idiopathic hyperaldosteronism (IHA, n = 3) after overnight rest in the supine position and after 4 h upright posture and furosemide administration. Plasma renin activity (PRA) and aldosterone (Aldo) levels were also determined. Compared to normal renin essential hypertension (33.6 +/- 2.2 pg/ml), basal plasma ANP was significantly higher in low renin essential hypertension (66.8 +/- 6 pg/ml), IHA (54.1 +/- 6.3 pg/ml) and APA before (62.4 +/- 4.9 pg/ml) but not after adrenal surgery (22 +/- 3 pg/ml). After upright posture and furosemide administration plasma ANP was decreased (p less than 0.01) in patients with low renin and, less markedly, with normal renin essential hypertension, however not in IHA and APA. In about half of the patients with low renin essential hypertension, unchanged PRA after upright posture and furosemide administration was associated with increased plasma Aldo and decreased ANP levels. We conclude that (i) the relatively high basal plasma ANP levels in low renin essential hypertension, IHA and APA may reflect the presence of volume expansion in these patients; (ii) the hormonal responses to upright posture and furosemide administration in patients with normal and low renin essential hypertension may indicate a counterregulatory role of ANP during activation of the renin-angiotensin-aldosterone system; (iii) the high plasma ANP, which is unresponsive to upright posture and furosemide administration, in patients with APA and IHA may be a potentially interesting new finding whose pathophysiological significance remains to be established.

Adult↗

PubMed1991

Digital cell image analysis of Ewing's sarcoma.

We analyzed the lesional tissue in Ewing's sarcoma by means of a cell image processor computing 15 nuclear parameters in order to quantify the morphologic variability of the tumor cell nuclei. To this end we combined 32 cases (350-400 Feulgen-stained nuclei analyzed per case) in a data file, which was then subjected to principal component and canonical analyses. We found considerable heterogeneity within the cell nucleus population of Ewing's sarcomas. Indeed, after the arbitrary subdivision of the file into two cell classifiers (CC1 and CC2 cell types) on the basis of the first canonical function, the 32 Ewing's sarcomas showed a great deal of variability in the proportion of CC1 and CC2 cell nucleus types. The nuclei of the CC1 type had a more finely textured chromatin when compared to the CC2 type, the nuclei of which exhibited a more granular chromatin pattern. Additionally, these 32 Ewing's sarcomas were characterized by three distinct DNA histogram types. Eight tumors displayed a diploid nonproliferating DNA histogram pattern (type A), 11 a diploid proliferating (type B) and 13 an aneuploid (type C) DNA histogram profile. We found a highly significant relationship between these DNA histogram types and the CC1:CC2 cell type percentage ratio. The eight Ewing's sarcomas with a type A DNA histogram contained a significantly higher proportion of CC1 cell type nuclei as compared to the 13 tumors with a type C DNA histogram, which contained a great proportion of CC2 cell type nuclei.

Cell Nucleus↗

PubMed1991

Comparison of fine needle aspirates of breast cancers to imprint smears by means of digital cell image analysis.

Morphonuclear assessments were performed using the SAMBA 2005 cell image processor on cell nuclei in fine needle aspirates and corresponding imprint smears from 17 not-otherwise-specified (NOS) breast carcinomas to study the influence of cell sampling on the morphonuclear measurements. Fourteen parameters related to densitometric (nuclear DNA content), morphometric (nuclear area) and textural (chromatin organization and distribution) characteristics were computed for each nucleus. The results demonstrated that such morphonuclear features evolved significantly and positively with respect to conventional histopathologic grading. The method of cell sampling significantly influenced the results, but without altering the general conclusions regarding evolution of the morphonuclear features.

Biopsy, Needle↗

PubMed1990

Characterization of human colorectal mucosa, polyps, and cancers by means of computerized morphonuclear image analyses.

Fifty-eight Feulgen-stained imprint smears from freshly resected colorectal tissue were analyzed by means of a SAMBA 200 cell image processor to establish a quantitative grading of their evolution from normal to malignant mucosa on the basis of 15 morphonuclear parameters relative to morphometry (nuclear size), densitometry (DNA content), and texture (chromatin pattern). The colorectal samples belonged to six groups: normal mucosa from patients without (Group 1) or with (Group 2) colorectal cancer, adenomas (Group 3), and cancers corresponding to the three stages of the Dukes' classification (Groups 4 to 6). Results indicated that analysis of the morphonuclear parameters computed on 250 to 300 nuclei/cases objectively and quantitatively showed the adenoma-cancer sequence. This need for only a small number of nuclei to assess a highly efficient analysis created a preoperative investigative tool using cytologic smears during endoscopy. The authors also made preliminary data banks for objective and reproducible grading of unknown cases by comparisons (discriminant analyses) with their contents. This approach must be validated prospectively on a large series of cases to furnish a system for colorectal malignancy diagnosis.

Cell Nucleus↗

PubMed1990

Influence of smear preparation and fixatives on the DNA ploidy and the morphonuclear features of the MXT mammary tumor and normal tissues in the mouse.

We compared cytomorphonuclear parameters--related to DNA histogram and chromatin distribution--on MXT mouse mammary tumor and murine normal cells from fresh squash smears or from deparaffinized tissue smears fixed in several fluids. We used the SAMBA 200 cell image processor with software allowing for the discrimination of parameters computed on Feulgen-stained nuclei. The spectrophotometric results--assessed by integrated optical density values--indicate that the nuclei from deparaffinized tissue fixed in Bouin's fluid are around 50% less stained than those fixed in formalin or ethanol-formalin-acetic acid (EFA). The fresh smears of nuclei fixed in formalin contain a less well-defined and more homogeneous chromatin than after Bouin's or EFA fixation. This has led to the conclusion that morphonuclear parameter comparisons performed on tissues differently processed or from different origins present severe limitations.

Adenocarcinoma↗

PubMed1990

Characterization of the morphonuclear features and DNA ploidy of prostatic disease.

The relationship between several morphonuclear parameters related to nuclear densitometry (DNA content and ploidy), and the chromatin pattern of Feulgen-stained nuclei is confronted to the histopathological grading of 39 prostatic samples obtained from surgical adenomatous or transurethral resection. We use a SAMBA 200 cell image processor with software allowing for the setting up of preliminary data banks that enable carrying out an objective and reproducible grading of unknown cases obtained from core biopsies of fine-needle aspirations. The present approach must be validated prospectively on a large series of cases in order to create an expert system for diagnosing such fine-needle aspirations from prostate.

Analysis of Variance↗

PubMed1990

Thyrotropin-releasing hormone increases plasma atrial natriuretic peptide levels in human.

The effect of thyrotropin-releasing hormone (TRH) on plasma atrial natriuretic peptide (ANP), TSH, prolactin, cortisol and aldosterone levels in 26 patients with normal pituitary and thyroid gland function was examined. Bolus iv injection of 200 micrograms TRH produced, between 0 and 60 min, a significant gradual rise of plasma ANP concentrations from 30.4 +/- 2.3 to 54.8 +/- 6.4 pg/ml (mean +/- SE). Plasma prolactin and TSH concentrations increased four- and six-fold of basal values with peak responses at 15 and 30 min, respectively, whereas plasma cortisol and aldosterone concentrations remained unchanged after the drug treatment. The patients had no significant changes in blood pressure or pulse rate. We conclude that there may be indirect mechanism(s) which result in increased ANP levels after TRH administration.

Adult↗

PubMed1990

Influence of hormono- and/or chemotherapy on the MXT mouse mammary tumor as monitored by 31P MRS.

We describe the early in vivo modifications that occurred in the MXT mouse hormone sensitive mammary tumor following various treatments which were monitored by 31P NMR spectroscopy. The MXT mouse mammary tumor was subjected to clinically relevant low-dose chemotherapy, i.e. seven cycles of 20 mg/kg cyclophosphamide (CPA) with or without an attempt at estrogenic cell recruitment prior to the CPA treatment. NMR measurements were begun at the end of the CPA treatment in order to evaluate the remaining 'long-term' chemotherapy-induced modifications within the MXT tumors. Statistical analyses performed on the 31P NMR parameters revealed that treatment had induced significant effects on bATP/PCr, Pi/PCr and PME/PDE only, with PCr being the most discriminating index. Its presence within MXT tumors was verified by means of an analysis of perchloric extracts. The results indicate a relative decrease of PME/PDE and a better conservation of PCr within the CPA-treated group as compared to the control one. This feature appeared even prior to any macroscopic modifications, as was the case within the group which contained tumors smaller than 120 mm2, and where no significant differences appeared between the mean sizes of the MXT cancers. In contrast, within the G2 group, which contained tumors equal to or larger than 120 mm2, CPA significantly slowed down tumor growth, while the administration of estradiol (E2) prior to CPA treatment antagonized the positive CPA-induced therapeutic effect. In conclusion, the non-invasive follow-up of the chemotherapeutic treatment of a clinically relevant mammary tumor model by 31P NMR spectroscopy backed up by statistical analyses revealed metabolic changes that appeared well before any modifications in histopathology or growth.

Animals↗

PubMed1990

Computerized morphonuclear cell image analyses of malignant disease in bladder tissues.

We analyzed the relationship between several morphonuclear parameters related to nuclear size, densitometry (deoxyribonucleic acid content and ploidy) and the chromatin pattern versus the histopathological grading of 46 bladder cancer samples graded according to the World Health Organization classification. We used a SAMBA 200 cell image processor with software allowing for the discrimination of 15 different parameters on Feulgen-stained imprint smears. In addition, we set up preliminary data banks that enable objective and reproducible grading of unknown cases. This approach must be validated in a large series of cases to create an expert system for bladder malignancy diagnosis.

Cell Division↗