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Biomedical subjects

N Ferrara

Publications and source records attributed to N Ferrara.

At least 37 records · Page 2Linked to original sources
PubMed1991

Dipyridamole echocardiography as a useful and safe test in the assessment of coronary artery disease in the elderly.

We prospectively studied the sensitivity, specificity, feasibility, and safety of high-dose dipyridamole echocardiography, compared to exercise electrocardiography in 130 subjects (67 younger and 63 elderly patients) referred for angiographic evaluation of suspected or proven coronary artery disease. Sensitivity, specificity, and feasibility of dipyridamole echocardiography were respectively 75.5%, 100%, and 88.0% in younger patients and 82.9%, 100%, and 79.4% in elderly patients (P = NS). The sensitivity of exercise electrocardiography was 72.7% in young and 66.6% in elderly patients (P = NS); specificity 66.0% vs 60.0% (P = NS); feasibility 83.6 vs 63.5 (P = 0.05). Forty-nine younger and 38 elderly patients performed both tests. Sensitivity of dipyridamole echocardiography compared to exercise electrocardiography was 76.2% vs 73.8% in young patients and 83.3% vs 70% in the older group (P = NS). The feasibility of the two tests was significantly different in the elderly group only (dipyridamole echocardiography 79.4% vs exercise electrocardiography 63.5%; P less than 0.01). The incidence of side effects during dipyridamole echocardiography was similar in the two groups, except for dyspnea which was observed in 20% of older and 5% of younger patients (P less than 0.05). Our data demonstrate that the dipyridamole test combined with echocardiographic monitoring of regional myocardial contractility may be considered a valid non-invasive method for evaluating coronary artery disease in the elderly and that this test is a satisfactory alternative to the exercise stress test.

Aged↗
PubMed1991

The hypothetical role of potassium conductance on the genesis of R-wave amplitude increase during ischemia in the isolated rat heart.

The effect of increased potassium conductance on the genesis of R-wave amplitude increase during acute myocardial ischemia has been studied in the isolated perfused rat heart by simultaneously recording the R-wave amplitude of epicardial electrograms (VEE), heart rate (HR), coronary flow rate (CFR), left ventricular diastolic pressure (LVDP), and left ventricular systolic pressure (LVSP). The experiments were performed during basal and partial or total ischemic conditions at spontaneous or fixed HR. In some experiments, potassium conductance was increased by means of high-calcium (8 mM) or acetylcholine chloride (10(-6) M) perfusion. In the control experiments, partial ischemic perfusion produced an increase in VEE and LVDP and a decrease in HR, CFR, and LVSP; total ischemic perfusion exaggerated these variations. High-calcium perfusion provoked an increase in VEE and LVDP and a decrease in HR, CFR, and LVSP during basal conditions (p less than 0.01 vs. control experiment); these modifications increased progressively during partial ischemic perfusion (p less than 0.01 vs. control experiment) and during total ischemic perfusion (p less than 0.01 vs. control experiment). Perfusion with acetylcholine chloride produced variations similar to those observed in high-calcium solution except that LVDP under basal conditions remained unchanged from control. When the HR was maintained at a constant value by means of atrial pacing the results were similar to those observed in the unpaced hearts. In conclusion, in the isolated perfused rat heart, increasing potassium conductance may influence the genesis of R-wave amplitude increasing during acute myocardial ischemia.

Acetylcholine↗
PubMed1991

The 16K fragment of prolactin specifically inhibits basal or fibroblast growth factor stimulated growth of capillary endothelial cells.

Intact 23 kilodalton (kDa), rat PRL is enzymatically cleaved in many target tissues to a 16 kDa (16K PRL) and an 8 kDa fragment. After reduction of an internal disulfide bond the fragments are released. 16K PRL was shown to be a potent mitogen on mammary epithelial cells via PRL receptors. Since estradiol-induced prolactinomas develop a new blood supply we tested the action of intact PRL and 16K PRL on growth of new vessels (angiogenesis). The angiogenic action of intact PRL and 16K PRL was tested in cultured bovine brain and adrenal cortex endothelial cells. Basal (b) or b-fibroblast growth factor (FGF) stimulated growth was estimated by counting cells or measuring the level of incorporation of 3H-thymidine into DNA. Paradoxically, 16K PRL inhibited the basal and FGF-stimulated growth of cultured endothelial cells in a dose-dependent fashion. Intact PRL or the cleaved but not reduced PRL were inactive even at a 100-fold higher concentration. When reformation of disulfide bonds was inhibited by carbamidomethylation of 16K PRL the preparations were more potent. 16K PRL had no effect on the mitogenic action of bFGF on baby hamster kidney cells which are known to have FGF receptors. These data demonstrate that in vitro 16K PRL is a potent and specific angiolytic factor, i.e. it inhibits angiogenesis. Furthermore, the action of 16K PRL does not appear to be via the known PRL or FGF receptors. Since angiogenesis is an essential component of tumor growth 16K PRL has potential as a therapeutic agent for the treatment of cancer.

Adrenal Cortex↗
PubMed1991

The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA.

Vascular endothelial growth factor (VEGF) was recently identified as a secreted, direct-acting mitogen specific for vascular endothelial cells and capable of stimulating angiogenesis in vivo. Molecular cloning revealed multiple forms of VEGF, apparently arising from alternative splicing of its RNA transcript. We have examined various human cDNA libraries by the polymerase chain reaction technique and discovered a fourth molecular form, VEGF206. This form contains a 41-amino acid insertion relative to the most abundant form, VEGF165, and includes the highly basic 24-amino acid insertion found in VEGF189. Southern blot analysis revealed that a single gene encoded these various forms, and nucleic acid sequence analysis of a portion of the VEGF gene revealed an intron/exon structure compatible with alternative splicing of RNA as a mechanism for their generation. Transient transfection of human embryonic kidney 293 cells showed that, like VEGF189, VEGF206 was predominately cell-associated and only very poorly secreted despite the presence of the signal peptide identical to that found in VEGF121 and VEGF165, both of which are efficiently exported from the cell. Vascular permeability activity was detected in the medium of 293 cells transfected with all four forms of VEGF; however, endothelial cell mitogenic activity was apparent only with VEGF121 and VEGF165. Thus, alternative splicing of VEGF RNA can produce four polypeptides with strikingly different secretion patterns, which suggests multiple physiological roles for this family of proteins.

Amino Acid Sequence↗
PubMed1991

Aortic smooth muscle cells express and secrete vascular endothelial growth factor.

We examined whether cultured bovine aortic smooth muscle (ASM) cells express VEGF. RNA blot analysis of total cellular RNA derived from ASM cells demonstrates the expression of the VEGF gene. ASM cells release in the medium a VEGF-like endothelial cell mitogen which binds to heparin-sepharose and has an apparent molecular weight of 40-45 kDa as assessed by an HPLC gel filtration column. Consistent with VEGF, this mitogen does not stimulate the proliferation of ASM cells. Immunoblot analysis of the bioactive material with an antibody specific for VEGF demonstrates the presence of a major immunoreactive band with an apparent molecular mass of 23 kDa and a minor band with a molecular mass of approximately 18 kDa, in reducing conditions. The major band has very similar apparent molecular weight as the 165 amino-acid species of human recombinant VEGF of folliculo-stellate cells derived VEGF. These data demonstrate the expression and synthesis of VEGF by cultured ASM cells and suggest that the 164 amino-acid species is the predominant molecular form of the growth factor secreted by such cells. VEGF released by ASM cells may play a paracrine role in the maintenance of the integrity of the endothelial lining or in the abnormal proliferation of the vasa vasorum which takes place in atherosclerosis.

Animals↗
PubMed1991

[Aging and left ventricular diastolic function].

Several studies have demonstrated that physiological aging significantly affects cardiovascular function. Experimental researches, conducted on cardiac muscle of senescent animals, have shown a prolongation of both contraction and relaxation times. This phenomenon was explained by a reduced Ca(++)-stimulated ATPase pump activity, responsible for the reduced sarcoplasmic reticulum Ca++ uptake rate. The myofilament response to Ca++ in the aging heart is normal as are peak contractile force production and post-extrasystolic twitch potentiation during continual paired stimulation. On the other hand, the inotropic response to cardiac glycosides and beta-adrenoceptor stimulation is diminished in senescent compared to adult myocardium. This decreased contractility could result mainly from mechanisms controlling Ca++ reuptake from sarcoplasmic reticulum and relaxation time (diastolic phase) rather than those determining force generation and contraction time (systolic phase). Age-related physiologic structural changes are not associated with significant variations in left ventricular diastolic and systolic sizes, but they seem a direct consequence of the rising systolic blood pressure observed in these age decades. Myocardial hypertrophy should not be considered a specific marker of the senescent heart, but rather an adaptive response to increased afterload conditions. As regard the relationship between age and diastole, it is important to underline that the alterations in aging cardiac muscle function primarily involve the isovolumic relaxation time and diastolic phase. With age, the early diastolic phase declines while the contribution of atrial contraction to ventricular diastolic filling increases as well as the isovolumic relaxation time.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1990

Vascular endothelial growth factor is expressed in rat corpus luteum.

In the course of the development of the ovarian follicle and differentiation of granulosa cells into corpus luteum (CL), extensive changes in the microvasculature of these structures take place. This suggests the local release of angiogenic factors. In the present work we examined whether a newly described secreted vascular endothelial growth factor (VEGF) is expressed in normal rat ovary by in situ hybridization. Our results demonstrate the expression of VEGF in the CL but not in mural granulosa cells, suggesting a temporal relation between VEGF expression and growth of capillary vessels. The hybridization pattern in the CL was consistent with localization of VEGF message to luteal cells. Expression of VEGF was detected also in cumulus oophorus cells. These findings suggest that VEGF is involved in the process of CL angiogenesis.

Animals↗
PubMed1990

Conditioned medium from mouse sarcoma 180 cells contains vascular endothelial growth factor.

Medium conditioned by mouse sarcoma 180 cells stimulates the growth of capillary endothelial cells. The growth factor produced by mouse sarcoma 180 cells is heparin-binding, dithiothreitol-sensitive, endothelial cell specific, and secreted into the medium. The characteristics of this mouse sarcoma-derived growth factor are very similar to those of vascular endothelial growth factor (VEGF) first described by Ferrara and Henzel (1989). The N-terminal amino acid sequences of the two growth factors are similar. Since the amino acid sequence of vascular permeability factor (VPF) is essentially identical to that of VEGF, a Western blot of mouse sarcoma 180-derived endothelial growth factor was probed with a polyclonal antibody raised against human VPF. This antibody reacted with several proteins of approximately 23 kDa, suggesting the presence of multiple forms of a VEGF-like protein. A full length cDNA probe for bovine VEGF reacted strongly with RNA isolated from mouse sarcoma 180 cells. We conclude that an endothelial growth factor found in conditioned medium from mouse sarcoma 180 cells is VEGF.

Amino Acid Sequence↗
PubMed1990

Arrhythmogenic age-related effects of lysophosphatidylcholine in the rat heart.

Ventricular arrhythmias are the most common cause of death among patients with coronary artery disease; this is more evident in the elderly, who tend to have more severe coronary artery disease and age-dependent modifications of cardiac electrophysiology. Lysophosphoglycerides, which accumulate in the ischemic myocardium, are responsible for oscillatory after-potentials and may contribute to the development of ventricular arrhythmias. The aim of this study was to examine the effects of lysophosphatidylcholine (5 x 10(-5) M) in the absence or presence of epinephrine (10(-6) M) in isolated, perfused hearts from adult (6-12 months old) and senescent (24 months old) rats. Rat hearts (30/group) were randomly divided into four groups each of which included hearts of 6, 12 and 24-month old rats. The groups comprised a control group, a group treated with epinephrine, a group treated with lysophosphatidylcholine and a group treated with both epinephrine and lysophosphatidylcholine. Analysis of arrhythmias indicated a linear correlation between epinephrine- and lysophosphatidylcholine-induced ventricular arrhythmias and age. The incidence of arrhythmias was higher in the hearts treated with epinephrine and lysophosphatidylcholine together than in those treated with either substance separately (p less than 0.01). The results indicate that age influences the arrhythmogenic action of lysophosphatidylcholine, and that epinephrine contributes to this effect.

Aging↗
PubMed1989

Vascular endothelial growth factor is a secreted angiogenic mitogen.

Vascular endothelial growth factor (VEGF) was purified from media conditioned by bovine pituitary folliculostellate cells (FC). VEGF is a heparin-binding growth factor specific for vascular endothelial cells that is able to induce angiogenesis in vivo. Complementary DNA clones for bovine and human VEGF were isolated from cDNA libraries prepared from FC and HL60 leukemia cells, respectively. These cDNAs encode hydrophilic proteins with sequences related to those of the A and B chains of platelet-derived growth factor. DNA sequencing suggests the existence of several molecular species of VEGF. VEGFs are secreted proteins, in contrast to other endothelial cell mitogens such as acidic or basic fibroblast growth factors and platelet-derived endothelial cell growth factor. Human 293 cells transfected with an expression vector containing a bovine or human VEGF cDNA insert secrete an endothelial cell mitogen that behaves like native VEGF.

Amino Acid Sequence↗
PubMed1989

Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells.

A growth factor for vascular endothelial cells was identified in the media conditioned by bovine pituitary follicular cells and purified to homogeneity by a combination of ammonium sulfate precipitation, heparin-sepharose affinity chromatography and two reversed phase HPLC steps. The growth factor was a cationic, heat stable and relatively acid stable protein and had a molecular weight, as assessed by silver-stained SDS-PAGE gel, of approximately 45,000 under non reducing conditions and approximately 23,000 under reducing conditions. The purified growth factor had a maximal mitogenic effect on adrenal cortex-derived capillary endothelial cells at the concentration of 1-1.2 ng/ml (22-26 pM). Further characterization of the bioactivity of the growth factor reveals that it exerts mitogenic effects also on vascular endothelial cells isolated from several districts but not on adrenal cortex cells, lens epithelial cells, corneal endothelial cells, keratynocytes or BHK-21 fibroblasts, indicating that its target cells specificity is unlike that of any previously characterized growth factor. Microsequencing reveals a unique N-terminal amino acid sequence. On the basis of its apparent target cell selectivity, we propose to name this factor vascular endothelial growth factor (VEGF).

Animals↗
PubMed1989

Fibroblast growth factor and the control of pituitary and gonad development and function.

Evidence from in vitro studies support the concept that growth factors could be involved in the development, maturation and function of endocrine organs. Included among the growth factors which are known to influence endocrine cell proliferation and differentiation is the fibroblast growth factor (FGF), which controls the proliferation, differentiation, and other functions of mesodermal- and neuroectodermal-derived cells. Its modulator, transforming growth factor beta (TGF beta), which determines the positive or negative direction of the effects of FGF, may play a role as well. In this review, we present a speculative view of how FGF in the pituitary gland, and both FGF and TGF beta in the gonads could influence the development and function of these organs through regulating mechanisms involving paracrine and autocrine control of cell proliferation and differentiation.

Aging↗
PubMed1988

Regulation of ion transport in hypophysial pars intermedia follicular cell monolayers.

We have previously reported that cultured monolayers of folliculo-stellate cells (FC) of adenohypophysial pars tuberalis (PT) and pars distalis (PD) origin express morphological and electrical properties typical of ion and fluid transporting epithelia. The objective of the present study was to examine whether cells expressing similar transport properties exist also in the pars intermedia (PI), an area of the adenohypophysis very poorly vascularized, where a cell type expressing such functions would be expected to play an especially significant role in the local regulation of the interstitial fluid content and circulation. Enzymatically and mechanically dispersed bovine pars intermedia fragments yield monolayers of polygonal, contact inhibited cells which rapidly develop domes. Such cells exhibit morphological features and growth properties very similar or identical to those expressed by cells previously identified af FC cells in PD and PT cultures. Similarly to their counterparts in the PD and PT, the PI FC display a potential difference and a resistance when mounted in Ussing chambers. Isoproterenol, prostaglandin E2, bradykinin and lysine vasopressin are able to stimulate active ion transport across FC monolayers. These data indicate that the PI contains ion transporting FC and suggest important local regulatory functions for these cells.

Animals↗
PubMed1988

Bovine brain astrocytes express basic fibroblast growth factor, a neurotropic and angiogenic mitogen.

Astrocytes derived from adult bovine corpus callosum contain large amounts of mitogenic activity for capillary endothelial cells and astrocytes. On the basis of radioimmunoassay, bioassay and immunoneutralization studies, 99.5% of this activity consists of basic fibroblast growth factor (bFGF). Immunoblot and gene expression analysis are also consistent with the synthesis of bFGF. The remainder of bioactivity [0.5%] is accounted for by acidic fibroblast growth factor (aFGF). These data suggest that astrocytes are a source of brain-derived bFGF and to a much lesser extent also of aFGF. Considering that bFGF has been proposed to play a role in the development and differentiation of the nervous system through its angiogenic and neurotropic properties, its presence in astrocytes provides a rationale for the complex regulatory and neurotropic functions attributed to these cells. Also, the ability of bFGF to stimulate the growth of astrocytes themselves suggest a role for the mitogen in normal and aberrant proliferation of astrocytes.

Animals↗
PubMed1988

Regional left ventricular mechanical function during isometric exercise in patients with coronary artery disease: correlation with regional coronary blood flow changes.

The effects of isometric exercise on regional left ventricular mechanical function and regional coronary blood flow were evaluated in 17 patients with significant proximal stenosis of the left anterior descending coronary artery and 10 patients with normal coronary arteriograms. All patients had normal myocardial contractility in the basal condition. All performed isometric handgrip exercise at 50% of the maximal voluntary contraction for 3 min during two-dimensional echocardiographic monitoring and hemodynamic evaluation of great cardiac vein flow by thermodilution technique. During isometric exercise, 7 of the 17 patients with left anterior descending coronary stenosis developed asynergy in the anterior territory (anterior or septal segment, or both) (group I); the remaining 10 showed normal myocardial contraction during the test (group II). The 10 normal subjects manifested no regional asynergy during the test (control group). The increase in great cardiac vein flow at peak isometric exercise was significantly smaller (p less than 0.01) in group I (+15 +/- 8%) than that in group II (+98 +/- 48%) and the control group (+64 +/- 22%). Anterior coronary vascular resistance decreased in group II (-32 +/- 13%) and in the control group (-25 +/- 8%) but increased in group I (+6 +/- 8%, p less than 0.01 versus group II and control group). These data demonstrate that handgrip-induced myocardial asynergy is associated, in our study patients, with an abnormal response of the regional coronary circulation. The increase in coronary vascular resistance in group I patients with asynergy demonstrates that functional mechanisms play a dominant role in left ventricular mechanical dysfunction induced by isometric exercise.

Aged↗
PubMed1988

Basic fibroblast growth factor: expression in cultured cells derived from corneal endothelium and lens epithelium.

We have examined the possible expression of fibroblast growth factor in cultured cells derived from bovine lens epithelium and corneal endothelium. Lens epithelial, but not corneal endothelial, cells were found to express the acidic fibroblast growth factor (aFGF) gene, whereas both cell types express the gene encoding basic fibroblast growth factor (bFGF), a related mitogen. Expression of bFGF was further examined. Both corneal endothelial and lens epithelial contain 3.7 and 7.0 k bFGF gene transcript, which are translated into material closely related, if not identical with bFGF. Essentially all of the bFGF-like material is bioactive, i.e. it can stimulate the proliferation of capillary endothelial or corneal endothelial cells and the stimulation is blocked by anti-bFGF antibodies. Our results indicate that bFGF derived from corneal endothelial and lens epithelial cells may act as a paracrine and autocrine growth factor in both cell types. Thus, bFGF present in both cell types may play an important role in the proliferation of injured or transformed ocular tissues.

Animals↗
PubMed1988

Diagnostic value of the ratio of recovery systolic blood pressure to peak exercise systolic blood pressure for the detection of coronary artery disease.

It has been previously reported that at treadmill exercise testing an abnormal ratio of recovery systolic blood pressure (SBP) to peak exercise SBP is more sensitive than exercise-induced angina or ST segment depression for diagnosing coronary artery disease (CAD). To investigate whether the SBP ratio keeps its diagnostic value during upright bicycle exercise, we evaluated the ratio of postexercise SBP to peak SBP in 73 patients with angiographically documented CAD and in 48 patients with normal coronary arteries (OV group) undergoing maximal stress testing on a bicycle ergometer. Three minutes after exercise ended, SBP ratio was significantly higher in the CAD than in the OV group (0.79 +/- 0.1 vs 0.71 +/- 0.08; p less than .001). Setting the upper normal limits of the recovery SBP ratio at 2 SDs from the mean for the OV group (SBP ratio = 0.98 and 0.88 at 1 and 3 min after exercise, respectively), with an increase or no change in SBP ratio at between 1 and 3 min of recovery considered an abnormal response, the sensitivity of SBP ratio was 30%, the specificity was 83%, and the accuracy was 51%. The respective values for ST depression were 81% (p less than .0001 vs SBP ratio), 48% (p less than .001 vs SBP ratio), and 67% (p less than .01 vs SBP ratio). Thus, for bicycle ergometer exercise testing, ST segment depression seems to be more accurate than SBP ratio in diagnosing CAD.

Adult↗