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Biomedical subjects

E Lengyel

Publications and source records attributed to E Lengyel.

At least 19 recordsLinked to original sources
PubMed1995

Involvement of a mitogen-activated protein kinase signaling pathway in the regulation of urokinase promoter activity by c-Ha-ras.

The expression of the urokinase-type plasminogen activator, which plays a crucial role in tissue remodeling by controlling the synthesis of the broadly acting plasmin serine protease, is regulated by several tyrosine kinases. Since the actions of these tyrosine kinases is dependent on the activation of ras proteins, we undertook a study to identify signaling events downstream of ras responsible for the stimulation of urokinase promoter activity. Transient expression of an activated c-Ha-ras in OVCAR-3 cells, which do not harbor the mutated oncogene, led to a dose-dependent trans-activation of the urokinase promoter. A sequence residing between -2109 and -1964 was critical for the stimulation of the urokinase promoter by c-Ha-ras. Mutation of an AP-1 and a PEA3 site at -1967 and -1973, respectively, or the co-expression of a transactivation domain-lacking c-jun substantially impaired the ability of c-Ha-ras to stimulate urokinase promoter activity. The induction of the urokinase promoter by ras was completely blocked by expression of a dominant negative c-raf expression vector and substantially reduced in cells made to co-express a catalytically inactive mitogen-activated protein kinase kinase. Further, the expression of an ERK1/ERK2-inactivating phosphatase (CL100) abrogated the stimulation of the urokinase promoter by c-Ha-ras. These data argue for a role of a mitogen-activated protein kinase-dependent signaling pathway in the regulation of urokinase promoter activity by ras.

Adenocarcinoma↗
PubMed1995

Stimulation of urokinase expression by TNF-alpha requires the activation of binding sites for the AP-1 and PEA3 transcription factors.

The urokinase-type plasminogen activator plays a central role in tissue remodeling by controlling the synthesis of the extracellular matrix-degrading plasmin. Urokinase expression is transcriptionally regulated by a variety of cytokines including TNF-alpha. The present study was undertaken to identify key transcription factor binding sites in the urokinase promoter necessary for the TNF-alpha-dependent induction of urokinase expression. TNF-alpha treatment of a squamous cell carcinoma cell line, UM-SCC-1, which produces no detectable TNF-alpha, led to a dose-dependent increase in urokinase secretion, thus reflecting a more abundant mRNA. Transient transfections of UM-SCC-1 cells with a CAT reporter driven by 5' deletion fragments of the urokinase promoter indicated that a sequence spanning -2109 to -1870, which contained binding sites for AP-1 and PEA3 was required for the stimulation by TNF-alpha. Mutation of an AP-1 binding site at -1967 and a PEA3 motif at -1973 completely abrogated the inductive effect of TNF-alpha on urokinase promoter activity. Mobility shift assays indicated the presence of a jun-containing factor(s) which bound specifically to the AP-1 sequence present in the urokinase promoter. The amount and/or activity of this factor(s) was greatly enhanced by TNF-alpha treatment. UM-SCC-1 cells transiently transfected with a CAT reporter driven by 3 tandem AP-1 binding sites demonstrated increased CAT activity following TNF-alpha treatment. Thus, the induction of urokinase expression by TNF-alpha is likely to involve the altered expression and/or activity of transcription factors which bind to the AP-1 and PEA3 target sequences in the urokinase promoter.

Base Sequence↗
PubMed1995

Induction of M(r) 92,000 type IV collagenase expression in a squamous cell carcinoma cell line by fibroblasts.

A previous investigation (Matsumoto et al., J. Oral Pathol. Med., 18: 498-501, 1989) has shown that the in vitro invasion of a collagen gel by squamous cell carcinoma can be substantially augmented in the presence of fibroblasts. Therefore, we undertook a study to determine if the production of collagenase(s) by a squamous cell carcinoma cell line, UM-SCC-1, was up-regulated by fibroblasts. Cocultivation of UM-SCC-1 cells with MDA-TU-138 fibroblasts, both established from the oral cavity, resulted in a dose-dependent increase in the activity of a M(r) 92,000 gelatinase as shown by zymography. Augmented M(r) 92,000 gelatinase activity was a consequence of the stimulation of the UM-SCC-1 cells by a soluble, fibroblast-derived factor since this effect could be reproduced with fibroblast-conditioned medium but not with glutaraldehyde-fixed fibroblasts. The increased M(r) 92,000 gelatinolytic activity could be accounted for by an increase in M(r) 92,000 type IV collagenase (MMP-9) protein, as demonstrated by Western blotting for this metalloproteinase. Trypsin treatment of the fibroblast-conditioned medium abolished its ability to increase MMP-9 secretion by UM-SCC-1 cells. Furthermore, fractionation of the fibroblast-conditioned medium revealed a M(r) 3,000-10,000 soluble factor(s) which was responsible for the augmented production of MMP-9 by UM-SCC-1 cells. To determine if the increased production of MMP-9, in response to the fibroblasts, was a consequence of increased promoter activity, UM-SCC-1 cells were transiently transfected with a chloramphenicol acetyltransferase reporter driven by the MMP-9 promoter and plated on plastic or on a monolayer of MDA-TU-138 fibroblasts. A 4-5-fold stimulation of MMP-9 promoter activity was observed with UM-SCC-1 cells plated with the MDA-TU-138 fibroblasts, when compared with similarly transfected cells recultured on plastic. In conclusion, we have demonstrated that MMP-9 expression in a squamous cell carcinoma cell line is augmented by a fibroblast-derived protein(s). This finding indicates a role for stromal cells in the regulation of MMP-9 expression in squamous cell carcinoma. The ability of fibroblasts to regulate MMP-9 expression in tumor cells in vitro may explain the observation that the amount of M(r) 92,000 type IV collagenase mRNA in tumor cells is highest at the tumor:stromal interface of resected squamous cell carcinoma.

Carcinoma, Squamous Cell↗
PubMed1994

Coronary arteriopathy after lymphatic blockade: an experimental study in dogs.

The effects of lymph stasis on the histological and biochemical properties of the coronary arterial wall and on the coronary circulation were studied in 72 dogs. Cardiac lymph stasis was produced in 52 dogs by cardiac lymphatic blockade whereas in 20 dogs only a sham operation was performed. Blockade of cardiac lymph drainage promoted characteristic injury to the coronary arteries including subendothelial edema with plasma inbibition, interstitial and intracellular edema in the tunica media with degeneration in the smooth muscle layer, swelling of the adventitial space with dilated lymph vessels and, later, fibrosis. The biochemical properties of the coronary arterial wall also were adversely affected by cardiac lymph stasis. Thus, the collagen and hexosamine content of the coronary arteries increased and the metabolism of the coronary wall shifted in an anaerobic direction. Whereas coronary blood flow was slightly decreased with lymph blockade, the coronary circulatory reserve capacity and the adaptability of the coronary vascular system was markedly reduced. The histological changes were most apparent in the smaller coronary arteries. The coronary microvasculature was also pathologically altered with the development of numerous coronary arteriovenous microshunts. These findings in conjunction with other experimental and clinical information suggest that impaired cardiac lymph drainage contributes to the pathogenesis and progression of coronary artery disease.

Animals↗
PubMed1993

Keratin expression reveals mosaic differentiation in vaginal epithelium.

OBJECTIVE: Analyzing the expression of keratins has proved to be valuable for identifying of pathways of epithelial differentiation. In stratified epithelia K10 and K13 are representative for either the keratinizing (epidermal-type) or the nonkeratinizing pathway. STUDY DESIGN: We have investigated keratin expression in "normal" vaginal epithelium from 30 women, applying two-color immunofluorescence with monoclonal antibodies to K10 and K13 on cryostat sections and cell smears. RESULTS: A differential expression pattern of vaginal cells dependent on their localization within the epithelium was found. In cells of the first suprabasal layers differentiation began and became identifiable by a weak expression of K13. The adjacent layers displayed cells that concurrently expressed K10 and K13. In contrast, cells within the superficial strata expressed exclusively either one of the two keratins. CONCLUSION: Thus vaginal epithelium appears to be mosaic in differentiation, showing simultaneous expression of keratins K10 and K13, thought to be representative for distinct routes of differentiation.

Adult↗
PubMed1993

Physiological age-related changes: cross-sectional and longitudinal studies.

Physiological age-related changes were investigated by cross-sectional and longitudinal studies. The data of the study were derived from volunteers admitted to the Gerontology Center in Budapest. In the follow-up study 864 subjects took part, and in the cross-sectional study 2,281 individuals. The 20-year longitudinal study and the cross-sectional examination showed that from a clinical standpoint the most important observation is that several biochemical data do not change with age. No changes were found in the values in erythrocyte sedimentation, hemoglobin, hematocrit, serum total protein, albumin, liver function, glucose, creatinine, triglyceride, and HDL-cholesterol levels. Changes were observed in the levels of HDL-cholesterol, immunoglobulins, rheumatoid factors, antinuclear factors, morphology of lymphocytes, serum TSH and T3 concentration, and systolic blood pressures.

Aged↗
PubMed1991

Lymphatic arteriopathy: damage to the wall of the canine femoral artery after lymphatic blockade.

The effect of lymph stasis on the histological, biochemical, and elastic properties of the femoral artery were studied after regional lymphatic blockade in 36 dogs. Dogs were sacrificed 4-21 days after operation. Histologic changes of the femoral arterial wall (interstitial edema, degeneration in the muscle layer or media, thickened adventitia with dilated lymph vessels, and fibrosis) developed after regional lymphatic blockade. Characteristic metabolic alterations of the arterial wall (anaerobic catabolism of carbohydrate, increased lactate and glycosamine content) accompanied the morphological changes. Distensibility of the femoral artery decreased and greater elastic stiffness developed after regional lymphatic blockade. These results in conjunction with other experimental and clinical data support the concept that insufficient lymphatic transport within the blood vessel wall may contribute to the genesis and progression of arteriopathies.

Animals↗
PubMed1985

Occurrence of anti-low density lipoprotein antibodies and circulating immune complexes in aged subjects.

The incidence of circulating immune complexes, anti-low density lipoprotein (LDL) autoantibodies and the anti-LDL activity of immune complexes was studied in healthy young and aged controls and in patients with vascular diseases. Circulating immune complexes (CIC) frequently occurred both in the young or old patient groups and in the aged healthy control groups, whereas they could not be found in the young controls. Marked differences were found in the incidence of anti-LDL antibodies between the groups tested. In both young and aged control groups such antibodies were very rarely observed (4-5%). In contrast anti-LDL antibodies were present in 35-45% in the aged, or young patients. Similarly, no anti-LDL activity was found in CIC of the controls, whereas in the patients with vascular diseases a significant CIC-associated anti-LDL activity was detected. These results suggest that the presence of anti-LDL antibodies are associated with the arteriosclerotic manifestations, while that of circulating immune complexes is connected by the ageing process itself.

Adult↗
PubMed1984

Antibody and immunoglobulin levels in aged humans.

IgM and IgG type antibody titers and levels of serum IgG, IgA and IgM were determined in healthy young and aged subjects. The proportion of subjects of low antibacterial agglutinin titers progressively increased during the 7th and 8th decades of life. Anti-streptolysin-O titers were also shifted to the lower values in aged subjects, at least until the 8th decade of life, although subnormal values compared to the young control range were less frequent than in the case of IgM type antibodies. Anti-streptokinase values did not seem affected by age. In contrast to antibody levels, serum IgM was similar or slightly higher in old compared to young subjects. Evidence is presented that the proportion of 7 S IgM drops with aging. Both IgA and IgG levels increased through the 7th, 8th and 9th decades of life. Different class immunoglobulin levels seemed to be considerably correlated and a tendency to correlate was found between IgG type antibody and serum IgG levels. Complex investigations including quantitation of antibodies to extrinsic and intrinsic antigens and serum immunoglobulins are proposed to define the humoral immune status of aged subjects and to understand the causes as well as the diagnostic and prognostic significance of old age 'imbalances'.

Adult↗
PubMed1983

Free and complexed anti-lipoprotein antibodies in vascular diseases.

The cell-mediated immune response against low density lipoproteins (LDL) was demonstrated by the migration inhibition test in patients with various vascular diseases. Anti-high density lipoprotein2 (HDL2) cellular immune response was found only in a few patients. LDL and HDL2 binding factors were detected in about 50% of coronary patients. No significant difference in their occurrence was found between the normolipidemic and hyperlipidemic patients nor between patients with hyperlipidemia type II/b and type IV. On the assumption that lipoproteins may act as auto-antigens by forming immune complexes, the presence of anti-LDL and anti-HDL2 activity was investigated in circulating immune complexes obtained by polyethylene glycol (PEG) precipitation from the sera of coronary patients and controls. Using an ELISA technique, PEG-precipitable anti-LDL activity was detected in 23, 11 and 18% of cases with myocardial infarction, angina pectoris and healthy old subjects, respectively. In the immune complexes obtained from the sera of the healthy young donors no anti-LDL activity was found. Anti-HDL2 activity in the immune complexes was demonstrated only in a few cases from among the patients and elderly persons we investigated.

Adult↗
PubMed1981

[Polyarthrosis of the hand (author's transl)].

The polyarthrosis of the hand is a typical disease of the old age. Its banal form is more frequent in women, its erosive type in men. It can be demonstrated not only on the interphalangeal joints but on the metacarpophalangeal joints as well. The degenerative process of the basal-joints of the first ray of the hand is often seen in polyarthrosis. Most frequently diagnostic problems are caused by the erosive arthrosis however first of all polyarthrosis has to be differentiated from the p.c.p.

Aged↗
PubMed1980

[Arthrosis of the first foot segment in aged patients (author's transl)].

Basing on x-ray and clinical examinations, the authors report on the incidence, distribution according to sex and age, and lateral localisation of arthrosis occurring in the first segment of the foot. The bilateral type of arthrosis mostly occurs as a result of hallux valgus and is seen in women. Furthermore, degnerative changes and structural modifications of the dislocated sesamoids are also frequent. Arthrosis associated with hallux rigidus is a degenerative process mainly found in men, which is exclusively unilateral. This degenerative process shows the classical clinical and x-ray signs pertaining to arthrosis

Age Factors↗
PubMed1980

[Lipoprotein examination in old hyperlipemic persons (author's transl)].

The fluorescence and thiobarbituric acid reaction of isolated beta lipoprotein (beta-LP) and alpha lipoprotein (alpha-LP) have been studied in young, old, and old hyperlipemic persons. Specific fluorescence showed no significant difference in the beta-LP of young and old individuals. However, the difference was signficant in the A:F 380:450 fluorescence (A= activation wavelength, F = fluorescence or emission wavelength) of the alpha-LP. On the effect of autooxidation the alpha-LP showed a significant increase in both the A:F 380:450 and the A:F 410:470 fluorescence. Absorption at 530 nm has been studied by the thiobarbituric acid (TBA) reaction. The malondialdehyde (MDA) content has been given as microgram/mg on the basis of the curve obtained by the known quantity of MDA. The MDA content of beta-LP in the young and old groups was less increased as compared to the substantial increase of alpha-LP. As opposed to results obtained in senile persons MDA increase of alpha-LP has been significant in old hyperlipemic individuals. In addition to the absorption peak at 530 nm, characteristic for MDA, a peak at 450 nm has been obtained by TBA. A yellow-brown substance associated with hyperlipemia did appear mainly in the protein fraction isolated from alpha-LP and has been named protein III. During oxidation in hydrochloric acid a yellow-brown substance appeared from protein III fraction and became unsoluble and dark brown in hyperlipemic persons. The substance was considered as a precursor of the atherofluorescent component (AFC) present in atherosclerotic aortas. The reaction in the alpha-LP, and particularly in its protein component, with MDA (originating from peroxidezed unsaturated fatty acids) leads to complexes which are, assumably, precursors of atheromatous lipid and calcium plaques.

Adolescent↗
PubMed1980

[Results of orthopedic and radiological investigations on the knee joint of old age patients (author's transl)].

Orthopedic and radiological investigations were performed on the knee joint of 200 old age patients. The majority of them had no or minute signs, and were free of symptoms. The X-ray characteristics of the degenerative changes of the old age patient's knee joints, and their relationship with the clinical findings are discussed too. The authors point to the relevance of prearthritic conditions in the pathogenesis of those serious osteo-arthritic changes, which become evident in advanced ages.

Aged↗