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Biomedical subjects

J Mester

Publications and source records attributed to J Mester.

At least 73 records · Page 4Linked to original sources

BALB/C mouse 3T3 fibroblasts expressing human estrogen receptor: effect of estradiol on cell growth.

Mouse 3T3 fibroblasts (clone A31) were stably transfected with human estrogen receptor (hER). Among the four sublines expressing functional hER at approximately 10(4) estrogen binding sites/cell, three retained a non-transformed morphology and growth characteristics while the fourth displayed a transformed phenotype (criss-cross growth, lack of density arrest, reduced dependence on exogenous growth factors). Estradiol (E2) had no effect on the growth of the three non-transformed hER expressing sublines. In contrast, low concentrations (1 to 20 nM) of E2 strongly inhibited the proliferation of the subline with transformed phenotype and high (100 nM) concentrations were toxic in these cells.

Animals↗

Upward creep of the heart in exercise thallium 201 single photon emission tomography: clinical relevance and a simple correction method.

The upward creep of the heart during myocardial single photon emission tomography (SPET) acquisition has been reported as a frequent source of false-positive results. The aim of this study was to simplify the detection and correction of this upward creep and to estimate its clinical relevance during routine patient care. To recognize the upward heart motion a straight line was fitted to the upper and lower border of consecutively displayed tomographic projection images. In this way, vertical translation of at least 1 pixel in size could be detected easily. On the assumption of a slow but continuous upward motion a fast interpolation correction method was developed. From 100 consecutive, supine, ergometric exercise studies, 1, 2 or 3 pixels of upward creep were found in 16, 4 or 3 patients, respectively. It was found that an upward creep of at least 2 pixels (7/100 cases) led to evident, mostly antero-septal defects on quantitative bull's-eyes, whereas only upward creeps of 3 pixels or more (3/100 cases) produced false-positive diagnostic results. The simple correction method offered a sufficient compensation of image and/or bull's-eye artefacts. These clinical findings could be reproduced in a computer model. Thus, it can be stated that clinically significant upward creep of the heart during stress SPET acquisition is relatively rare; it may have been overestimated in the past, and its artificial effects can be corrected by a quick and simple algorithm.

Algorithms↗

Insulin/insulin-like growth factor I induce actin transcription in mouse fibroblasts expressing constitutively myc gene.

Quiescent benzo[alpha]pyrene-transformed BALB/c 3T3 fibroblasts (line BP-A31), continue to express 'competence' genes (such as c-myc) and do not require platelet-derived growth factor ('competence' factor) in order to resume the cell division cycle. Insulin-like growth factor I (IGF-I), as well as insulin (at high concentrations, where it interacts with IGF-I-receptors) are potent mitogens in these cells. In contrast with the original non-transformed A31 cell line, we show that insulin/IGF-I (even in the absence of de novo protein synthesis) induce actin transcription in BP-A31 cells. We have verified that 'CArG' boxes, major actin promoter elements, can act as insulin-inducible elements in BP-A31 cells. Insulin-induced actin transcription is also observed in quiescent A31 cells stably transfected with a myc expression vector, suggesting a correlation between constitutive myc expression and insulin-induced actin transcription.

Actins↗

Antimitogenic effects of dexamethasone in chemically transformed mouse fibroblasts.

Dexamethasone (a synthetic glucocorticoid) inhibited the entry into the S-phase of quiescent chemically transformed mouse fibroblasts (BP-A31) stimulated with 12-O-tetradecanoyl 13-acetate (TPA; a protein kinase-C activator) or with basic fibroblast growth factor. The basal rate of DNA synthesis was also strongly reduced by dexamethasone. In contrast, the mitogenic activity of insulin (acting via the insulin-like growth factor-I receptor) was little or not at all affected by dexamethasone. The antimitogenic activity of dexamethasone was enhanced when the steroid was included in the culture medium 24 h before the addition of mitogens. The effects of dexamethasone were glucocorticoid specific, partially reversed by the antiglucocorticoid RU 486, and prevented by cycloheximide (suggesting the involvement of glucocorticoid-induced protein synthesis in the antimitogenic activity of dexamethasone). Under the conditions of exponential growth in serum-free medium as well as in the presence of TPA, dexamethasone arrested the proliferation of sparsely seeded cells after a delay of 24-48 h. The BP-A31 cells are known to be constitutively competent and express at quiescence certain genes related to the G0/G1 transition in the original nontransformed A31 cell line. Of the transcripts corresponding to these genes, dexamethasone caused a rapid elimination of the JE mRNA, coding for a protein of the family of cytokines. The cell content of c-jun mRNA was also strongly reduced in the cells incubated at quiescence with dexamethasone (in the absence of mitogen). The presence of TPA along with dexamethasone prevented the elimination of c-jun, but not of JE mRNA. Short (30-min; together with the inducers) or long (24-h) treatment of the cells with dexamethasone did not prevent the induction of the c-fos gene expression by either TPA or basic fibroblast growth factor, indicating that dexamethasone does not interfere with mitogenic signal transduction. We conclude that in TPA-stimulated cells, the antiproliferative effect of dexamethasone is not due to interference with the expression of the c-jun gene, but may be related to the decreased level of the JE cytokine mRNA as well as to the synthesis of growth inhibitory protein(s).

Animals↗

[Isolated right ventricular infarction].

Generally, right ventricle infarction is accompanied by left ventricle infarction. Isolated right ventricle necrosis is rare. Among 1707 patients with 6-week-old myocardial infarction there were 2 cases with isolated right ventricle infarction. Diagnosis based on pathologic Q waves in right precordial chest wall leads, radionuclide and echocardiographic observations. In one case, diagnosis was supported by coronary angiography, too.

Adult↗

[Stress tolerance in patients with right ventricular infarct during the rehabilitation period].

199 patients with myocardial infarction were divided into 4 groups according to the localisation of necrosis (anterior, inferior, anterior + right ventricle, inferior + right ventricle). Exercise capacity was determined by bicycle ergometer test at the beginning of rehabilitation and 3 weeks later. Exercise capacity and ejection fraction were better in case of inferior comparing with anterior infarction. There was no significant change in exercise capacity whether inferior or anterior left ventricle necrosis was accompanied by right ventricle infarction. In chronic phase of myocardial infarction exercise capacity of patients is not influenced by right ventricle necrosis accompanied by left ventricle infarction.

Exercise Test↗

[Cardiolite (99m-Tc-isonitrile) SPECT studies in patients prior to coronary bypass surgery].

The authors studied with 99m-Tc Cardiolite (methoxy-isobutyl-isonitrile) SPECT examination the effect of coronary bypass operation on the myocardial perfusion. One week before and 3 weeks after the operation examinations were performed first with dipyridamol loading and 24 hours later in rest. The regional perfusion of the myocardium was studied on the basis of transversal section-pictures of corrected axis position. In the examinations preceding the operation the global sensitivity of the method was found to be 100%. In the demonstration of the structures of the ramus descendens 95%, of the ramus circumflexus and of the right coronary artery 100% sensitivity was reached. In postoperative examinations following the bridging of the ramus descendens anterior the improvement of the perfusion of the corresponding ventricular segment was found in 15/20 during the loading and in 7/8 cases following the bridging of the ramus circumflexus and right coronary artery. Improving perfusion was demonstrated in 17/20 and in 6/8 cases in rest. On the basis of the results the authors consider their method suitable for the study of the regional blood perfusion and for the examination of the changes taking place upon coronary bypass operations.

Aged↗

Butyrate blocks the accumulation of CDC2 mRNA in late G1 phase but inhibits both the early and late G1 progression in chemically transformed mouse fibroblasts BP-A31.

Sodium butyrate (6 mM) blocks the resumption of the cell division cycle in serum-deprived chemically transformed Balb/c-3T3 mouse fibroblasts (BP-A31). The inhibition of G1 progression by sodium butyrate is not restricted to a specific mitogenic signaling pathway and is equally effective when tetradecanoyl phorbol acetate (TPA), insulin, or fetal calf serum (FCS) is used as inducer. The inhibitor acts in early as well as late G1 phase as indicated by experiments in which inhibitor was added and withdrawn at different times after restimulation of quiescent cells by FCS. At the gene expression level, sodium butyrate does not affect the inducibility of early cell cycle-related genes (c-myc, c-jun) while blocking the induction of cdc 2 mRNA, a late G1 marker. We conclude that sodium butyrate does not interfere with the growth factor signaling pathways regulating the (early) cell cycle-related gene expression. However, the presence of sodium butyrate early in G1 phase inhibits the cascade of events leading eventually to the expression of late G1-characteristic genes such as cdc2. The antimitogenic activity of sodium butyrate may be related to its interference with an (unknown) process involved in the "mitogenic" cascade.

Animals↗

Differentiation of newborn rat preadipocytes in culture: effects of insulin and dexamethasone.

A preadipocyte cell population isolated from the inguinal tissue of 3-day-old rats converts at confluence into mature adipocytes when cultured with insulin (10(-9) M). Insulin is necessary only from Day 4 postplating. If the addition of insulin is further delayed, the proportion of cells which will undergo adipose conversion decreases. A loss of the differentiation competence is also observed when the cells are allowed to proliferate (seeding at a low density in a serum containing medium). A preexposure of the primary cells to dexamethasone during the insulin-insensitive period (Days 0-4) accelerates the subsequent "insulin-dependent" adipose conversion. In order to produce its effect, dexamethasone needs only to be present for 4 h on Day 2 postplating. The effect of dexamethasone is probably due neither to inhibition of cell proliferation nor to induction of the cell content of insulin receptors. The evolution of G3PDH enzyme activity as well as of G3PDH protein and mRNA was used as an indicator of the differentiation process. The enzyme accumulates to a low extent during culture in the absence of insulin. When insulin is present, the enzyme level is dramatically increased (maximum on Day 11). Dexamethasone pretreatment (Days 0-4, or 4 h on Day 2) accelerated the G3PDH enzyme activity increase as well as protein and mRNA accumulation. This was also true in cells maintained in insulin-free medium; however, in this case, the increase in the enzyme activity was limited to the first 8 days of culture and full differentiation did not take place. We conclude that: (1) the rat preadipocytes are committed to differentiate, requiring insulin as a sufficient physiological stimulus; (2) the differentiation program is progressively lost after greater than 4 days of culture without insulin and more rapidly if the cells are allowed to undergo divisions; and (3) dexamethasone accelerates the insulin-dependent adipose conversion but alone does not ensure the complete differentiation process.

Adipose Tissue↗

Significance of DNA content abnormalities in small rectal cancers.

Several studies have shown that the presence of DNA content abnormalities, measured by flow cytometry, may correlate with a poor prognosis in a variety of cancers. The predictive value of DNA content in patients with small rectal cancers has not been well determined. Thirty-nine patients with primary rectal adenocarcinoma smaller than 3 cm were studied in a comparison of DNA content with established prognostic variables. The following covariates were evaluated for their prognostic value: sex, age, tumor size, location, distal margin, Dukes' classification, tumor differentiation, and DNA content. DNA content was assessed by flow cytometric analysis, and each tumor was categorized as diploid or nondiploid. Of the parameters studied, Dukes' classification and tumor DNA content were found to be independent prognostic indicators. Determination of DNA content seems to provide additional useful prognostic information in patients with small rectal tumors.

Adenocarcinoma↗

Reconstruction of Fourier coefficients: a fast method to get polar amplitude and phase images of gated SPECT.

Gated SPECT (GASPECT) during radionuclide ventriculography (RNV) is a time-consuming procedure requiring extended hard- and software. Furthermore, the procedure suffers from poor count statistics. Our method tries to overcome these difficulties by exploiting the count summation effect of Fourier analysis. The sine and cosine coefficients of the first harmonic are extracted from the gated views and reconstructed. This, in fact, results in an improvement of the count statistics by a factor of four combined with a tremendous reduction of disc space requirements. Using short-axis slices, bull's-eye plots of the amplitude and phase of the left ventricle are calculated. Cardiac functions and localization and extent of any malfunction are documented three-dimensionally without superposition.

Data Interpretation, Statistical↗

[The effect of 3-dimensional data stabilization in radionuclide ventriculography on the statistical numerical error in the ejection fraction].

The suitability of a 3-dimensional filter in diminishing the statistical noise of left ventricular volume curves without any systematical error in the left ventricular ejection fraction (EF) was investigated. The EF values were compared in 50 studies on 24 patients. There was no significant systematical difference between the EFs before and after filtering. The filter diminishes the statistical uncertainty of the EF by a factor of 0.47. Therefore, the method may possibly be employed in processing the left ventricular volume curves.

Adult↗

Proliferation of the human colon carcinoma cell line HT29: autocrine growth and deregulated expression of the c-myc oncogene.

Human colon adenocarcinoma cell (line HT29) are able to proliferate in a defined (serum-free) medium containing no added growth factors; in such conditions, their doubling time is 3 to 4 days (on serum-coated dishes) or 2 to 3 days (on an autologous extracellular matrix) compared with 1 day in the presence of fetal calf serum. In the presence of suramin, a polyanion disrupting the binding of growth factors to their receptors, the incorporation of [3H]thymidine in serum-free cultures is reduced (27.0 +/- 2.9% of control after 3 days of culture), suggesting involvement of autocrine growth factors in the autonomous proliferation of the cells. The expression of the proliferation-related oncogene c-myc was examined during various stages of growth and differentiation of the HT29 cells. The cellular contents of c-myc mRNA were similar in all experimental conditions studied: exponential phase; stationary phase; nondifferentiated as well as differentiated cells (by glucose deprivation); and also in serum-free medium containing or not suramin. An approximately 2-fold increase in the level of c-myc mRNA was observed in cells cultured for 3 days in suramin-containing medium and then incubated during 3 h in the absence of suramin (with or without 10% fetal calf serum). Southern blot analysis of the genomic DNA of HT29 cells did not reveal any rearrangement within the region containing the c-myc gene and the flanking sequences (approximately five kilobases upstream and approximately three kilobases downstream). The c-myc locus was weakly amplified (four to six copies per cell). These results indicate that the c-myc gene expression in HT29 cells is deregulated and does not require growth factor stimulation. The deregulation of the c-myc gene may be related to the reduced growth factor requirement of the HT29 cell line.

Blotting, Northern↗

Mitogenic activity of phorbol esters and insulin-like growth factor 1 in chemically transformed mouse fibroblasts BP-A31: independent effects and differential sensitivity to inhibition by 3-isobutyl-1-methyl xanthine.

Mitogenic effects of agents activating either the protein kinase C (PDGF; phorbol esters) or the insulin-like growth factor 1 (IGF1)-receptor pathway were studied in quiescent chemically transformed mouse fibroblasts (BP-A31), by evaluating the rate of [3H]thymidine incorporation. Each of these pathways alone was found to be sufficient to sustain progression through the entire cell division cycle. The mitogenic activity of phorbol 12-myristate 13-acetate (PMA) but not that of insulin was blocked by staurosporine (an inhibitor of protein kinase C), in support of the notion that protein kinase C activation was required for the PMA-induced cell cycle progression. The mitogenic effects of PMA were potentiated by cycloheximide pretreatment, and they were abolished by 3-isobutyl-1-methyl xanthine (IBMX; a cyclic nucleotide phosphodiesterase inhibitor). PDGF (known to activate the phospholipase C-protein kinase C pathway) also displayed mitogenic activity in the cycloheximide-pretreated BP-A31 cells, and its effects were prevented by IBMX. In contrast, the mitogenic effects of insulin (at concentrations where it activates the IGF1 receptor) or of IGF1 neither were notably influenced by cycloheximide pretreatment nor were inhibited by IBMX (in the presence of IBMX, the onset of S-phase was delayed by several hours). The expression of the c-fos gene was absent at quiescence; its induction by growth factors was not proportional to their mitogenic potency. Thus, c-fos expression was strongly induced by PMA but only weakly by insulin. IBMX was a powerful inducer of c-fos gene expression but caused a decrease in the level of c-myc mRNA.

1-Methyl-3-isobutylxanthine↗

Hypertension screening in a Hungarian town.

In conjunction with a radiological tuberculosis project, a hypertension screening programme was carried out in 1984 on 13,772 people (74% of the eligible adult population) in the Hungarian town of Csongrád. In the younger age groups the blood pressure was found to be higher amongst men, whilst in older groups the women had higher blood pressures. By the WHO criteria, systolic hypertension was detected in one-third of the population and diastolic hypertension in one-sixth. Of the hypertensive patients detected, 34% were previously unaware of their diagnosis. The prevalence of hypertension was elevated particularly amongst obese persons and in the sub-group of physical (blue collar) workers aged over 60 years. There was a significant correlation between alcohol consumption and both systolic and diastolic blood pressures. Hypertension was found in 29.9% of heavy drinkers but in only 20.5% of moderate drinkers or total abstainers.

Adolescent↗