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M Petein

Publications and source records attributed to M Petein.

At least 55 records · Page 3Linked to original sources
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

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↗
PubMed1992

New relationships between prostatic intraepithelial neoplasia and prostatic carcinoma.

Our group has been studying the progressive molecular changes in prostatic epithelium which precede the invasive phenotype. Initial studies revealed similar alterations in cytoskeletal proteins between high grade prostatic intraepithelial neoplasia (PIN) lesions and invasive carcinoma. Specifically we observed an increased expression of certain cytokeratins and decreased expression of vimentin. We also noted a change in glycosylation as detected by Ulex europaeus staining. Using the latter technique we were able to microdissect and isolate nuclei from areas of low and high grade PIN lesions as well as from invasive carcinoma for morphometric analysis. Similarities in nuclear size, chromatin heterogeneity, and nuclear DNA content between low and high grade PIN and invasive carcinoma in carcinomatous specimens were noted. In contrast, these parameters were significantly different in low grade PIN lesions obtained from benign prostatic transurethral resection (TURP) specimens. In addition, DNA histograms revealed similar proliferative indices between high grade PIN and invasive carcinoma, which differed significantly from low grade PIN. Parameters thought to be relative to the invasive phenotype were also examined, such as the members of the metalloproteinase family; although normal luminal cells fail to express detectable levels of these enzymes, invasive carcinoma and even low grade PIN lesions express both the 72 kDa and 92 kDa type IV collagenase. Taken together, these data indicate that the dysplastic cells of PIN lesions and carcinomas are similar in nuclear and genomic features as well as protease expression. Our current working hypothesis is that these cells are already armed with the necessary proteases to invade the basal lamina but in an inactive form. Tumor progression requires an additional event of protease activation.

Carcinoma↗
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↗
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

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↗
PubMed1987

Hemodynamic and regional blood flow response to piroximone (MDL 19,205) in dogs with congestive heart failure: a comparison with dobutamine.

This study compares the effects of piroximone (MDL 19,205), a new inotropic agent, with dobutamine in dogs with congestive heart failure. With dobutamine, (15 micrograms/kg/min) left ventricular (LV) dp/dt increased from 2220 +/- 215 (mean +/- S.E.M.) to 2815 +/- 280 mm Hg/sec and cardiac index increased from 2.9 +/- 0.2 to 3.7 +/- 0.4 liters/min/m2, whereas LV filling pressure was essentially unchanged (18.7 +/- 2.6-16.3 +/- 2.4 mm Hg). The hemodynamic effects of piroximone (50 micrograms/kg/min) were more pronounced. LV dp/dt increased from 2615 +/- 260 to 3760 +/- 410 mm Hg/sec and cardiac index from 3.0 +/- 0.1 to 4.4 +/- 0.6 liters/min/m2, whereas LV filling pressure decreased from 15.6 +/- 2.4 to 6.4 +/- 1.8 mm Hg (all P less than .05). Systemic vascular resistance index decreased from 2730 +/- 225 to 1905 +/- 256 dynes sec cm-5 m-2. Regional blood flow to the myocardium increased 48% with dobutamine and 24% with piroximone, whereas skeletal muscle flow increased 59% with dobutamine and 36% with piroximone. Renal blood flow remained unchanged with either drug. We conclude that piroximone is an inotropic agent with vasodilator properties that has an interesting hemodynamic profile somewhat similar to that of dobutamine but with the advantage of being orally active; therefore piroximone could be useful in the treatment of heart failure.

Animals↗
PubMed1986

31P NMR measurement of ATP synthesis rate in perfused intact rat hearts.

Using 31P NMR and the saturation-transfer method, the unidirectional rate of ATP synthesis was measured in isolated, Langendorff-perfused, isovolumic rat hearts operating at a rate pressure product of 25.6 +/- 2.5 (SE) X 10(3) mmHg X min-1 and consuming O2 at a rate of 35 +/- 2 mumol O2 X min-1 X (g dry wt)-1, at 37 degrees C. This rate was 7.2 +/- 0.9 mumol X s-1 X (g dry wt)-1 and was related to the rate of oxygen atom consumption by a ratio of 6.3 +/- 0.9. These data show that in the intact heart the unidirectional rate of ATP synthesis exceeds the net rate of ATP synthesis and consumption by approximately a factor of 2.

Adenosine Triphosphate↗
PubMed1986

Measurement of an individual rate constant in the presence of multiple exchanges: application to myocardial creatine kinase reaction.

Forward [creatine phosphate (CP)----adenosine 5'-triphosphate (ATP)] and reverse (ATP----CP) fluxes of myocardial creatine kinase (CK) measured by using 31P nuclear magnetic resonance (NMR) and conventional saturation transfer (CST) methods are unequal; this is a paradoxical result because during steady state fluxes into and out of the CP pool must be the same. These measurements, however, treat the CK reaction as a two-site exchange problem and ignore the presence of the ATP gamma in equilibrium Pi exchange involving the ATPases. We have applied a method [Uğurbil, K. (1985) J. Magn. Reson. 64, 207] based on the saturation of multiple resonances, by which a single unidirectional rate constant can be measured unequivocally in the presence of multiple exchanges, to the measurement of CK fluxes in isovolumic rat hearts perfused under three different conditions; two of the three perfusion conditions showed a large discrepancy in the CK fluxes determined by CST, and one did not. In contrast, when the effect of the ATP gamma in equilibrium Pi exchange on the CK rate measurements was eliminated, multiple saturation transfer (MST) measurements on the same hearts yielded equal forward and reverse fluxes in all cases. The rate constant for the ATP gamma----CP conversion measured by MST was larger than the value obtained by the conventional methodology whereas both methods gave the same rate constant in the CP----ATP direction. These results demonstrate that the cause of the paradoxical data obtained by CST measurements of CK kinetics is the ATP gamma in equilibrium Pi exchange and that CK rates when determined rigorously are consistent with the CK reaction being in equilibrium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1986

Persistent hemodynamic effects without long-term clinical benefits in response to oral piroximone (MDL 19,205) in patients with congestive heart failure.

Piroximone (MDL 19,205), a new phosphodiesterase inhibitor with positive inotropic and vasodilating properties, was administered orally to 12 patients with severe congestive heart failure (NYHA class III to IV). After a mean dose of 1.7 +/- 0.4 (SD) mg/kg, cardiac index increased from 2.0 +/- 0.5 to 3.0 +/- 0.6 liters/min/m2 while pulmonary wedge pressure decreased from 23 +/- 6 to 15.6 +/- 7 mm Hg and systemic vascular resistance from 1520 +/- 370 to 1000 +/- 320 dyne-sec-cm-5. Mean arterial pressure was slightly reduced from 80 +/- 13 to 75 +/- 11 mm Hg and forearm blood flow increased by 79% (all p less than .01). Eleven patients were selected for long-term treatment. Two patients received a heart transplant soon after the treatment was started. The remaining nine patients were followed for a mean of 5.6 months (range 2 to 10). Severe congestive heart failure recurred in eight of these nine patients, resulting in the death of three patients within 4 months. The remaining six patients underwent repeat hemodynamic evaluation 2 months after the initiation of the treatment. A short-term hemodynamic response to the drug in this group demonstrated that piroximone retains its circulatory effect during continuous therapy. Nevertheless, three more patients of this group died within 8 months and two required heart transplants. Of the nine patients receiving long-term treatment, only one had sustained subjective improvement and increased exercise capacity. Therefore long-term therapy with piroximone did not appear to benefit patients with severe congestive heart failure. A drug-related deterioration of their clinical status cannot be excluded.

Administration, Oral↗
PubMed1984

High resolution proton NMR studies of perfused rat hearts.

High resolution 1H NMR spectra of perfused rat hearts have been obtained under normoxic, ischemic and hypoxic conditions. Several myocardial metabolites including taurine, carnitine, lactate and tissue glycerides are detected in the 1H NMR spectra. Changes in oxygen availability induce perturbations in the levels of some metabolites, in particular, lactate. Experiments with fasted rats and with substrate-free perfusion suggest that the glycerides detected in 1H spectra are metabolically mobilizable but have a slow rate of turnover. These results demonstrate that utility of 1H NMR in monitoring myocardial metabolism.

Animals↗
PubMed1984

Hemodynamic effects of a new inotropic agent, piroximone (MDL 19205), in patients with chronic heart failure.

The hemodynamic and neurohumoral effects of cummulative intravenous doses of piroximone (MDL 19205), a noncatecholamine, nonglycoside, imidazole derivative with positive inotropic and vasodilating properties, were studied in eight patients with severe congestive heart failure. A dose of 1.25 mg/kg in seven patients and 1.75 mg/kg in one patient increased cardiac index by 75% from 1.96 to 3.41 liters/min per m2 and decreased systemic vascular resistance (-41%), right atrial (-66%) and pulmonary wedge pressure (-35%) (all p less than 0.005). Mean arterial pressure was slightly reduced from 78 to 71 mm Hg (p less than 0.05) and forearm blood flow increased by 42%. Plasma norepinephrine decreased from 830 to 542 pg/ml (p less than 0.05) and plasma renin activity tended to increase. In four patients, dobutamine (15 micrograms/kg per min) produced a comparable increase in cardiac index (+100%), but less decrease in pulmonary wedge pressure (-21 versus -41%, p less than 0.05 versus piroximone) and, unlike piroximone, significantly increased heart rate (+22%, p less than 0.05 versus piroximone) and heart rate-blood pressure product (+30%, p less than 0.01 versus piroximone). In four other patients, a single intravenous dose of piroximone (1 mg/kg) resulted in a 35% increase in the first derivative of left ventricular pressure (dP/dt) from 796 to 1,068 mm Hg/s (p less than 0.01). Thus, piroximone is a potent inotropic agent with an acute hemodynamic profile that may be more favorable than that of dobutamine. Because the drug is orally absorbed, clinical trials of chronic efficacy are indicated.

Adult↗
PubMed1984

Early changes in sodium and water balances in patients with acute myocardial infarction: relationship to haemodynamics and creatine kinase.

The changes in sodium and water balances during the first 4 days after an uncomplicated transmural myocardial infarction (MI) were determined in forty patients. The sodium balance was positive 4 days after MI in 80% of the patients but negative in 20%. Neither in anterior (n = 23) nor in inferior (n = 17) MI were rank correlations found between the haemodynamic parameters (cardiac index, mean arterial pressure, mean right atrial or pulmonary capillary pressures, right or left ventricular work indices) and sodium balance. However, the sodium balances correlated with the total creatine kinase (CK) release in anterior MI after 1 day (r = 0.60; P less than 0.002) and after 4 days (r = 0.65; P less than 0.001) but not in inferior MI. Furthermore, in anterior and inferior MI matched for their CK release, the sodium handling was different both after 1 day (-70 in anterior v. +44 mmol (24 h)-1 in inferior MI; P less than 0.001) and after 4 days (-36 v. +147 mmol (72 h)-1; P less than 0.01), a difference unexplained by differences in medical management or in sodium intake. Finally, sodium balance correlated with the changes in left ventricular stroke work index (LVSWI) observed during this period (r = 0.48, P less than 0.001), LVSWI being more stable when sodium balance was more positive. In conclusion, sodium balance after uncomplicated acute MI is related to MI location, to the size of anterior MI, and cannot be predicted from initial haemodynamics. Finally, the relation between LVSWI stability and positive sodium balance suggests that arbitrary sodium restrictions or diuretics might be deleterious to the haemodynamics after uncomplicated myocardial infarction.

Adult↗
PubMed1983

Effects of chronic volume overload on left ventricular response to tachycardia.

The aim of the study was to determine the effects of chronic volume overload on the inotropic response of the left ventricle to a change in frequency of stimulation. Ten normal dogs (normal) and eight dogs with a chronic left ventricular (LV) volume overload (aortocaval fistula) were studied by cardiac catheterization after sedation with morphine (1 mg/kg). In normal dogs, increasing heart rate from 122 to 172 beats/min produced insignificant changes in peak +dP/dt (+2%; NS) or (dP/dt)/DP40 (+6%; NS). In volume overload, these indexes increased by 16% (P less than 0.01) and 31% (P less than 0.01), respectively, when heart rate increased from 135 to 173 beats/min. Conversely, the poststimulation potentiation appeared greater in normal than in volume overload; (dP/dt)/DP40 increased by 40% in normal vs. 1% in volume overload (P less than 0.01). These differences between normal and volume overload persisted after propranolol (1 mg/kg) and atropine (0.25 mg) administration. In both groups, AR-L115 BS, a nonsympathomimetic positive inotrope with caffeinelike properties, reduced the inotropic response to tachycardia, thereby normalizing the peak +dP/dt changes in volume overload. We conclude that the positive inotropic effects of tachycardia are enhanced in LV volume overload. Changes in LV compliance or alterations in the cellular mechanisms responsible for the force-frequency phenomenon might explain these findings.

Animals↗