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L Rappaport

Publications and source records attributed to L Rappaport.

At least 37 records · Page 2Linked to original sources
PubMed1997

Increased expression of fibronectin isoforms after myocardial infarction in rats.

Fibronectin is a known chemoattractant for several cell types which play a role in the wound healing process, like fibroblasts, endothelial cells and macrophages. In addition, fibronectin generates a scaffold to which other extracellular matrix components can attach. The possible involvement of fibronectin in the wound healing process after myocardial infarction (MI) was investigated by studying the expression of fibronectin isoforms after induction of a MI in the rat. Deposition of plasma (pFN) and cellular fibronectin (cFN) protein was determined immunohistochemically, using monoclonal antibodies specific for cFN and polyclonal anti-human total FN (tFN antibodies). Expression of the mRNAs of total cFN and the embryonic isoforms EIIIA and EIIIB was investigated, using in situ hybridization (ISH). The ratio between EIIIA containing fibronectin (EIIIA+-FN) mRNA and total cFN mRNA was determined using a semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). cFN protein was present from day 4 until day 35 after infarction and was located around the area of infarction, in the epi- and endomyocardium and in the wall of larger vessels. pFN was found in the infarcted cardiomyocytes 1 day after the induction of the MI. From day 4 on pFN protein deposition was found in the border zone of the infarction and in the wall of larger vessels. pFN immunoreactivity remained present at high levels around the area of infarction and in the vessel wall throughout the entire period of investigation (90 days). From day 35 after the infarction pFN protein was detected in cardiomyocytes of the right ventricle and septum. cFN mRNA, determined by in situ hybridization, was present in the border zone of the infarcted area as early as 1 day after MI, and its expression peaked at 4 days after MI. Four days after MI the mRNA's coding for both the embryonic isoforms EIIIA and EIIIB could also be detected in the same area. Because expression of the EIIIA isoform was more abundant than the EIIIB isoform we only determined the percentage of the EIIIIA containing isoform from total FN. EIIIA+ mRNA was elevated 1 day after MI. We conclude that various fibronectin isoforms including the embryonic isoforms accumulate in the heart after MI. This suggests that these isoforms may play a role in the wound healing process in the left ventricle of the infarcted heart.

Animals↗
PubMed1997

Differential roles of AT1 and AT2 receptor subtypes in vascular trophic and phenotypic changes in response to stimulation with angiotensin II.

The aim of this study was to investigate the roles of angiotensin II (Ang II) receptor subtypes 1 (AT1) and 2 (AT2) in producing vascular wall hypertrophy and qualitative changes in smooth muscle cell gene expression. Wistar rats were treated for 23 days with osmotic minipumps containing solvent and either Ang II (120 ng.kg-1.min-1) or PD123319 (30 mg.kg-1.d-1), an AT2 receptor antagonist. In addition, rats receiving solvent and either Ang II or PD123319 were given losartan, an AT1 receptor antagonist, in the drinking water (10 mg.kg-1.d-1). Vascular wall hypertrophy and smooth muscle phenotype were characterized by morphometric analysis combined with immunohistochemistry. Ang II-induced hypertension was associated with the development of medial hypertrophy of the aorta and coronary arteries accompanied by reversion of vascular smooth muscle cells (VSMCs) toward an immature phenotype, as shown by the expression of cellular fibronectin and nonmuscle myosin. Losartan treatment, which restored normal arterial pressure, prevented all these changes. PD123319 treatment, which had no effect on blood pressure, prevented only vascular hypertrophy, with no effect on VSMC phenotype. Administration of only losartan to normal rats reproduced the Ang II-induced vascular hypertrophy, with no effect on VSMC phenotype. Taken together, these results suggest that (1) the trophic effect of Ang II on VSMCs is mediated via AT2 receptor subtypes and (2) changes in VSMC phenotypes are triggered mainly through AT1 receptor subtypes.

Angiotensin II↗
PubMed1997

Trophic effect of human pericardial fluid on adult cardiac myocytes. Differential role of fibroblast growth factor-2 and factors related to ventricular hypertrophy.

Pericardial fluid (PF) may contain myocardial growth factors that exert paracrine actions on cardiac myocytes. The aims of this study were (1) to investigate the effects of human PF and serum, collected from patients undergoing cardiac surgery, on the growth of cultured adult rat cardiac myocytes and (2) to relate the growth activity of both fluids to the adaptive changes in overloaded human hearts. Both PF and serum increased the rate of protein synthesis, measured by [14C]phenylalanine incorporation in adult rat cardiomyocytes (PF, +71.9 +/- 8.2% [n = 17]; serum, +14.9 +/- 6.5% [n = 13]; both P < .01 versus control medium). The effects of both PF and serum on cardiomyocyte growth correlated positively with the respective left ventricular (LV) mass. However, the magnitude of change with PF was 3-fold greater than with serum (P < .01). These trophic effects of PF were mimicked by exogenous basic fibroblast growth factor (FGF2) and inhibited by anti-FGF2 antibodies and transforming growth factor-beta (TGF-beta), suggesting a relationship to FGF2. In addition, FGF2 concentration in PF was 20 times greater than in serum. On the other hand, the LV mass-dependent trophic effect, present in both fluids, was independent of FGF2 concentration or other factors, such as angiotensin II, atrial natriuretic factor, and TGF-beta. These data suggest that FGF2 in human PF is a major determining factor in normal myocyte growth, whereas unidentified LV mass-dependent factor(s), present in both PF and serum, participates in the development of ventricular hypertrophy.

Adult↗
PubMed1997

HR 720, a novel angiotensin receptor antagonist inhibits the angiotensin II-induced trophic effects, fibronectin release and fibronectin-EIIIA+ expression in rat aortic vascular smooth muscle cells in vitro.

The aim of this study was to evaluate the direct trophic effects of angiotensin II (AII) on rat vascular smooth muscle cells obtained from a single cellular isolate. Cell volume, protein synthesis, fibronectin (FN) release and FN-EIIIA+ mRNA isoform expression were analyzed in parallel. The effects of HR 720, a novel AT1 angiotensin receptor antagonist with some AT2 receptor affinity, were compared with those of selective AT1 antagonist EXP 3174. Both HR 720 and EXP 3174 inhibited in a concentration-dependent manner the maximum increase in cell volume induced by 10(-9) M Sar1-All (IC50 = 0.49 x 10(-9) M and 0.79 x 10(-9) M, respectively). Maximum [3H]leucine incorporation was also achieved at 10(-9) M All. HR 720 blocked the increase in protein synthesis with potency similar to EXP 3174; the respective IC50 values were 1.04 x 10(-9) M and 1.36 x 10(-9) M. All dose-dependently increased FN release, which was also equally inhibited by about 50% with both compounds at 10(-6) M. Furthermore, All enhanced FN-EIIIA+ mRNA in rat vascular smooth muscle cells (VSMC), which indicated a modulation of FN isoform expression which was inhibited by angiotensin II antagonists. In conclusion, All induced parallel and concentration-dependent increases in cell volume, protein synthesis, FN release and FN-EIIIA+ mRNA expression in vascular smooth muscle cells. These effects appeared to be essentially mediated by AT1 receptor stimulation as indicated by the equal inhibitory effects of HR 720 and EXP 3174.

Angiotensin II↗
PubMed1997

Prognostic factors for alarm treatment.

A review of the literature concerning the use of enuresis alarms highlighted the lack of standardised definitions used to define enuresis and the insufficient understanding of the working mechanisms of alarms. Although first reported in 1904, enuresis alarms were not in routine use until the 1930's. Sensors in the bed or underwear, in conjunction with audible warning devices are the most common types of alarms. The alarm success rate of approximately 75% is independent of the type of alarm and there is a low relapse rate. In predicting alarm response, studies utilizing multivariate analysis techniques are superior to univariate techniques, but no one or combination of predictor variables is currently known to predict outcome accurately enough to alter standard clinical decision making. It is imperative that definitions are standardized and that study protocols are applied uniformly to well-defined populations that have a better potential response to enuresis alarms-the best intervention currently available.

Behavior Therapy↗
PubMed1996

Can grafted cardiomyocytes colonize peri-infarct myocardial areas?

BACKGROUND: Cell transplantation is emerging as a potential means of improving repair of damaged organs. This preliminary study tests the feasibility of grafting allogenic cells into the border zone of a myocardial infarct (MI). METHODS AND RESULTS: Neonatal cardiomyocytes were obtained from fetuses of female rats 20 days pregnant. They were then injected at three different sites (2 x 10(6) cells per site) into the left ventricular (LV) myocardium of control rats (n = 10) or of rats in which MI had been created by proximal occlusion of the left coronary artery (n = 10). In the latter case, injections were placed along the peri-infarct border zone. Half of each batch of cells was grown in culture to provide a control for cell morphology and viability. Six additional rats were injected with the culture medium alone. Forty-eight hours after injection, LV slices were processed for histological (hematoxylin-eosin) and immunohistological (sarcomeric alpha-actinin transplantation and laminin staining) techniques. Examination of serial sections from injected regions showed that grafted myocytes were harbored into the host LV myocardium in all control animals and at the border zone in 50% of the infarcted rats. Grafted cells were identified by their morphological characteristics and an immunohistological pattern of loose myofibrillar organization similar to that seen in cells concomitantly grown in culture. Injection of the culture medium alone had no effect but allowed us to rule out needle-related injury. CONCLUSIONS: These initial results suggest the feasibility of transplanting allogeneic cardiomyocytes into the border zone of MI areas, a prerequisite for this approach to successfully improve the function of ischemically damaged hearts.

Animals↗
PubMed1995

Accumulation of fetal fibronectin mRNAs after balloon denudation of rabbit arteries.

BACKGROUND: Fibronectin (FN), a component of the extracellular matrix, influences cellular migration and differentiation. It is a prominent component of the extracellular matrix of normal arteries and is thought to play an important role in the pathogenesis of restenosis after angioplasty. FN exists in multiple forms that arise from a single RNA transcript that can be alternatively spliced. EIIIA- and EIIIB-containing FN mRNAs predominate in the embryo, whereas in the adult, most of the normal tissue FN lacks these domains. Since few data were available concerning pattern of expression of the different alternatively spliced forms of FN mRNA in arteries after endoluminal injury, we analyzed the expression of EIIIA and EIIIB FN isoforms at different times after experimental angioplasty. METHODS AND RESULTS: The spatial and temporal alterations in FN expression were studied in an in vivo model of endothelial denudation in the rabbit aorta and iliac artery by a combination of immunochemistry and in situ hybridization methods. Alternatively spliced forms of FN EIIIA and EIIIB were detected in the media and the adventitia of both types of vessels 24 to 48 hours after injury. Two weeks after injury, EIIIA and EIIIB mRNAs were found to accumulate within the luminal layers of the neointima. The cellular form of FN protein was not found until 2 weeks after the injury and accumulated in the inner part of the neointima. CONCLUSIONS: These data demonstrate that FN upregulation is an early and long-lasting process after arterial injury. These results suggest that the induction of the embryonic FN isoforms may be involved in the restenotic process that follows balloon denudation of arteries.

Animals↗
PubMed1995

Fibronectin expression during physiological and pathological cardiac growth.

Fibronectin (FN) is a dimeric glycoprotein found in the extracellular matrix of most tissues that serves as a bridge between cells and the interstitial collagen meshwork and influences diverse processes including cell growth, adhesion, migration, and wound repair. Multiple FN forms arise by the alternative splicing of a primary transcript originating from a single gene. The spatial and temporal alterations in FN expression in the myocardium has been studied in models of cardiac growth in vivo such as fetal development, and hypertrophy secondary to pressure overload. This review focuses on the differential expression of FN isoforms that are observed in different models of cardiac growth. Using a combination of qualitative and quantitative analyses it is shown that in the rat myocardium: (1) the FN phenotype is developmentally regulated, (2) the re-expression of the fetal FN isoforms is observed in different models of cardiac hypertrophy secondary to a sudden or progressive hypertension and (3) the changes in cardiac FN expression affect mostly the coronary artery smooth muscle cells.

Alternative Splicing↗
PubMed1995

Fibronectin expression in the cardiovascular system.

Fibronectin (FN) is a dimeric glycoprotein found in the extracellular matrix (ECM) of most tissues and serves as a bridge between cells and the interstitial collagen meshwork. It also influences diverse processes including cell growth, adhesion, migration, and wound repair. Multiple FN forms arise by the alternative splicing of a primary transcript originating from a single gene. The spatial and temporal alterations in FN expression in the cardiovascular system have been studied in vitro in cell culture and in vivo during fetal development, hypertrophy, infarction, arterial injury and aging. This review describes characteristics of FN expression in cardiovascular system: 1. the FN phenotype is regulated during development. A high FN mRNA level is related to an early cardiac organogenesis and a progressive decrease that begins at the fetal stage and continues through senescence. During cardiac ontogeny, there is a linear correlation between total FN mRNA accumulation and the relative amounts of FN-EIIIA and EIIIB RNA. This correlation is absent during cardiac growth in the adult. 2. A differential reexpression of the FN isoforms is observed in both myocardium and aorta in different models of hypertension or infarction but with different threshold and time course. Changes in total FN mRNA levels in hypertensive models vary depending on the authors. Nevertheless the differences in the expression of the fetal forms of FN mRNA observed among the various models of hypertension-induced hypertrophy indicate that the process of FN pre-mRNA splicing in the adult myocardium is specifically regulated and depends on the pathological situations and the type of cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Pediatric compliance and the roles of distinct treatment characteristics, treatment attitudes, and family stress: a preliminary report.

Much research and clinical practice derives from the assumption that there is a set of psychological-social variables that commonly influence medical (non)compliance. This assumption may lead to overly general strategies for managing specific illnesses in children with chronic illness. With this concern in mind, a study was made of health provider ratings of compliance, treatment attitudes, and illness-related family stress for three pediatric cohorts (N = 75, ages 8 to 20 years): boys with hemophilia (n = 31), sickle cell disease (n = 22), or asthma (n = 22). Between-group differences were found on compliance and treatment attitudes (p < .05), with patients with sickle cell demonstrating greater treatment cooperation than their counterparts and boys with hemophilia expressing more positive outlooks on medical advice and about health outcomes (Newman-Keuls test, p < .05). Positive treatment attitudes were associated with specific compliance behaviors for boys with hemophilia (p < .045) but not for other groups.

Adaptation, Psychological↗
PubMed1994

In situ mRNA distribution of sarco(endo)plasmic reticulum Ca(2+)-ATPase isoforms during ontogeny in the rat.

The Sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) plays a crucial role in maintaining the Ca2+ homeostasis, which itself, controls various essential cellular function. The existence of several SERCA isoforms, encoded by three different genes and produced by alternative splicing of pre-mRNA transcripts, has been established by cDNA cloning. However, the temporo-spatial evolution of their expression during ontogeny was unknown. We have used in situ hybridization to determine the cellular distribution of three of these mRNA isoforms, SERCA 2a, SERCA 2b and SERCA 3 during rat ontogeny and focused our study on the cardiovascular system. We demonstrate that early in embryogenesis, SERCA 3 mRNA is highly expressed in the heart tube and is also present in the yolk sac. In 14-16 days embryos, SERCA 3 mRNA has disappeared from the heart but is expressed in the aorta and in discrete foci of the liver. Later on, its expression in the cardiovascular system is restricted to the arterial endothelium. SERCA 2a mRNA is coexpressed with SERCA 3 mRNA in the heart tube and remains expressed in the cardiomyocytes throughout life. It is transiently expressed in skeletal muscle at the onset of differentiation. In early foetal life, SERCA 2b is expressed in the mesenteric area and thereafter in all cell types at various levels. Our data indicate that (i) expression of SERCA 2b is neither tissue-specific nor developmentally regulated (ii) expression of SERCA 2a and SERCA 3 isoforms is regulated in a cell specific manner during development and suggest that the SERCA 3 gene plays a role in controlling the function of endothelial cells during vasculogenesis.

Aging↗
PubMed1994

Expression of fibronectin during rat fetal and postnatal development: an in situ hybridisation and immunohistochemical study.

OBJECTIVE: Fibronectin is a protein of the extracellular matrix with numerous binding sites to the other elements of the matrix and to the cells. The aim of this study was to determine the relative importance of fibronectin isoform expression (FN-EIIIA, FN-EIIIB) during fetal and postnatal development of the rat heart. METHODS: In situ hybridisation and immunolabelling approaches were used to describe the cellular synthesis of fibronectin and its distribution throughout the rat heart from 11 d postconception until adulthood. The distribution of fibronectin was compared to that of laminin and of alpha type III procollagen. RESULTS: The accumulation and pattern of distribution of the major fibronectin mRNA isoforms were identical, that is, there was a progressive decrease in their accumulation as a function of time after 11 d postconception, resulting in a complete absence in the adult. The distribution of fibronectin and procollagen type III mRNAs were, however, quite distinct. At the protein level the time course of synthesis and secretion of the locally synthesised fibronectin (c-FN) did not follow fibronectin mRNA expression, the accumulation of the protein being rather poor, except just before birth, where it was found mainly in the coronary vessels. CONCLUSIONS: During the development of the fetal rat heart fibronectin gene transcription is active and progressively decreases with age, whereas the translation of the mRNAs into their corresponding proteins is always relatively poor. If fibronectin is involved in fetal and postnatal morphogenesis of the rat myocardium, it is the plasma form (p-FN) that is most probably involved in the process of growth and differentiation of the rat heart.

Animals↗
PubMed1994

Differential splicing of fibronectin pre-messenger ribonucleic acid during cardiac ontogeny and development of hypertrophy in the rat.

BACKGROUND: Fibronectin, an extracellular matrix protein, exists as multiple isoforms expressed in a time- and cell-dependent manner. Since the developmental pattern of fibronectin expression has not been determined in the heart, the first issue of this study was to investigate the expression of total fibronectin mRNA as well as its isoforms during cardiac ontogeny. In adults, pressure overload induces a shift towards the fetal form of proteins expressed by either muscle or nonmuscle cardiac cells. Fetal forms of fibronectin mRNA being found in smooth and nonmuscle cardiac cells soon after imposition of pressure overload, the pattern of fibronectin expression during the development of pathological growth was analyzed to determine whether the two conditions of cardiac growth resulted in an identical pattern of fibronectin expression. EXPERIMENTAL DESIGN: Total RNA were isolated from rat heart (a) during in utero and postnatal life and (b) at varying periods of time after imposition of a pressure overload induced by coarctation of the thoracic aorta in 25-day-old rats. Fibronectin-EIIIA+ or -EIIIB+ and total fibronectin mRNAs were quantitated by reverse transcription-polymerase chain reactions and dot-blot analysis, respectively. RESULTS: Fibronectin mRNA, abundant in the 14-day-old fetal heart, rapidly decreased during cardiac physiologic growth (> 5-fold); no changes in the fibronectin mRNA level was observed during the development of pressure-induced cardiac hypertrophy. The percentages of fibronectin transcripts containing EIIIA or EIIIB exons, very high in the early fetal heart (> 45%), harmoniously decreased during cardiac maturation (< 12%). Aortic coarctation resulted in an early, transient (12 to 48 hours) and preferential expression of fibronectin-EIIIA+ mRNA (approximately 40%). CONCLUSIONS: In rat heart, neither physiologic nor pressure-induced growth requires increased amounts of fibronectin mRNA but the growth conditions specifically modulated the fibronectin pre-mRNA splicing.

Animals↗
PubMed1993

The sarco(endo)plasmic reticulum Ca(2+)-ATPase mRNA isoform, SERCA 3, is expressed in endothelial and epithelial cells in various organs.

The sarco(endo)plasmic reticulum Ca(2+)-ATPase mRNA isoform, SERCA 3, was previously shown to be expressed in a great variety of muscle and non-muscle tissues [(1989) J. Biol. Chem. 264, 18568] but its cellular localization within these organs was unknown. We have used in situ hybridization and RNase protection techniques to demonstrate that SERCA 3 mRNA is expressed in specific cell types, namely the endothelial and epithelial cells.

Animals↗
PubMed1993

Laminin variants and integrin laminin receptors in developing and adult human smooth muscle.

Distribution of laminin variant chains and of laminin-binding beta 1-associated alpha integrin subunits was studied in human arterial and visceral smooth muscle during development using the immunofluorescence method. In aortic media of 10-week-old fetuses (early fetal stage of development), B1, B2, and A chains were found, and at 27 weeks of gestation (late fetal step), in addition, the S chain was revealed. In the major part of adult aortic media, staining for the B1 chain was substituted by staining for the S chain. A reasonable explanation for this is that the basement membrane of arterial SMCs contains the A-B1-B2 laminin trimer at the early fetal stage of development, a mixture of A-B1-B2 and A-S-B2 variants during the late fetal period, and the A-S-B2 form in adult media. In the intimal thickening of adult arteries, staining for A and S chains was decreased, and the B1 chain was detected, thus suggesting coexistence of A-B1-B2 and A-S-B2 variants similar to the fetal aorta. These data led us to propose that maturation of arterial SMCs is accompanied by a switch from expression of A-B1-B2 to A-S-B2 laminin, the only protein variant associated with the differentiated SMC phenotype. The M chain was not detected in fetal and adult arterial smooth muscle. In differentiated visceral SMCs from adult colon, in contrast to arterial medial SMCs, B1, S, B2, and A chains, i.e., both B1 chain- and S chain-containing laminin molecules, were present. Similar to vascular smooth muscle, the expression of A and S laminin chains in SMCs of the intestine was developmentally regulated. Of the four beta 1-associated alpha integrin subunits that have been shown to recognize laminin (alpha 1, alpha 2, alpha 3, and alpha 6), only alpha 1 was revealed during the early fetal stage of development in smooth muscle of the arteries and digestive tract. alpha 3 appeared in aortic media only during the late fetal period. In adult arterial media and smooth muscle of the colon, alpha 1 and alpha 3 were the major potential laminin-binding integrins. The spatial-temporal distribution of laminin variants in developing and adult smooth muscle suggests that a variant laminin (possibly A-S-B2) interacting with its receptor (alpha 1 beta 1 or alpha 3 beta 1) may be important for maintenance of the differentiated SMC phenotype in vivo.

Adult↗
PubMed1993

Contractile protein gene expression in serum-free cultured adult rat cardiac myocytes.

The effects of two adhesion substrates (serum and laminin) and time in culture on the expression of genes encoding myosin heavy chain (MHC) isoforms and alpha-skeletal actin were analysed in myocytes isolated from adult rat heart and maintained in serum-free culture. Relative messenger ribonucleic acid (mRNA) abundances were quantitated by dot-blot analysis. Gene expression was not influenced by the substrate used. Time in culture induced a decrease in total mRNA abundance and an up-regulation of beta-MHC and alpha-skeletal actin genes. It is proposed that atrophy of adult myocytes is associated with a pattern of gene expression similar to the fetal program.

Actins↗