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Biomedical subjects

N Esposito

Publications and source records attributed to N Esposito.

29 records · Page 2Linked to original sources
PubMed1995

The proline-rich region of the GH receptor is essential for JAK2 phosphorylation, activation of cell proliferation, and gene transcription.

Mutational analysis of the proximal transmembrane region of the cytoplasmic domain of the GH receptor (GHR) allowed us to characterize box 1, a proline-rich sequence of eight amino acids, which has been shown to be critical for signal transduction of many cytokine receptors. Mutants of the box 1 region of the rat GHR were studied for their ability to initiate the phosphorylation of JAK2 and the proliferation of stably transfected BAF B03 cells and also the activation of Spi 2.1 gene transcription in transiently transfected Chinese hamster ovary (CHO) cells. Convergence of effects of the box 1 mutants on JAK 2 phosphorylation, cell proliferation, and gene transcription was found. Our results suggest that no single amino acid in the box 1 sequence is essential for signaling and that the last two prolines (PXP motif) and the hydrophobic residues are necessary for integrity of box 1. Box 1 represents a structural determinant, potentially able to provide an interaction between JAK2 and the receptor; this interaction could be direct or indirect via an adaptor protein.

Amino Acid Sequence↗
PubMed1994

Coronary artery vasoconstriction after successful single angioplasty of the left anterior descending artery.

Percutaneous transluminal coronary angioplasty is associated with spontaneous transient vasoconstriction. The mechanisms by which coronary vasoconstriction occurs distally to a successful dilated stenosis after coronary artery angioplasty are still unknown. The present study was planned to investigate the effect of successful coronary artery angioplasty on coronary vasomotion distal to a dilated stenosis and in the control vessel and the role of alpha-adrenergic receptors on coronary vasomotion after successful coronary artery angioplasty. We prospectively studied 32 consecutive patients scheduled for elective single coronary artery angioplasty of the left anterior descending coronary artery. Only aspirin, 325 mg, or nitroglycerin was allowed in the week before the study; no premedication with diazepam or other drugs was given. In group 1 (control patients, n = 20), quantitative coronary angiography was performed in the control state; 5 and 15 minutes after coronary artery angioplasty; and after intracoronary nitroglycerin infusion, 300 micrograms. In group 2 (n = 12), intracoronary phentolamine, 2 mg, was infused regionally through the balloon catheter before the coronary artery angioplasty, and coronary angiography was performed at baseline, 15 minutes after balloon deflation, and after nitroglycerin infusion. In group 1, constriction of the coronary segment distal to a dilated stenosis (2.4 +/- 0.8 to 2.1 +/- 0.6 mm, -14.6% vs baseline; p < 0.05) and of the circumflex coronary artery segment (2.8 +/- 0.7 to 2.5 +/- 0.6 mm, -10.7% vs baseline, p < 0.05) occurred 15 minutes after coronary artery angioplasty. The degree of vasoconstriction was not correlated with the lesion severity before coronary artery angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1994

Expression of two isoforms of the human growth hormone receptor in normal liver and hepatocarcinoma.

In man, two isoforms of growth hormone receptor (GHR) have been reported. The first, hGHR corresponds to the original form described by Leung et al. (J. Biol. Chem. 264 (1987) 9905-9910). The second, hGHRd3, missing 22 N-terminal amino acids is encoded by an mRNA derived from alternative splicing and deletion of the third exon. This latter form has been isolated from placenta and its tissue distribution, as well its function warrant further examination. We studied the relative expression of the two isoforms of GHR in liver at various stages of development of differentiation. Several samples from fetal livers and hepatocarcinomas were analysed and we observed that hGHR and hGHRd3 can be expressed solely or coordinately. Furthermore, we investigated the possibility that alternative splicing of exon 3 could be related to the specific use of different promoters. Our data show that both isoforms have identical 5'-untranslated regions in normal liver or in hepatoma cell lines. Finally, these experiments strongly suggest that hGHRd3 is efficiently translated as a functional receptor, with the soluble form of GHR being recovered in the cell media. The results of the present study support the concept that both isoforms are expressed in human liver, with exon 3 alternative splicing being neither tissue specific nor related to hepatic differentiation.

Alternative Splicing↗
PubMed1994

Influence of reversible segmental left ventricular dysfunction on heart period variability in patients with one-vessel coronary artery disease.

OBJECTIVES: This study evaluated the relation between reversible segmental left ventricular dysfunction and frequency domain measures of heart period variability in patients with coronary artery disease. BACKGROUND: Heart period variability is frequently reduced in patients with coronary artery disease. However, the mechanisms of this reduction are still unclear. METHODS: Echocardiographic left ventricular wall motion and frequency domain measures of heart period variability were evaluated in 32 patients with one-vessel coronary artery disease before and 16 to 24 days after successful percutaneous transluminal coronary angioplasty. Of these, 12 patients (Group A) had normal and 20 patients (Group B) had abnormal regional wall motion. A control group of 15 healthy subjects (Group C) underwent 24-h Holter recording twice at 2-week intervals to check for spontaneous variations. RESULTS: At baseline, low and high frequency power were lower in Group B than in Groups A and C, whereas no difference was detectable in ultra low and very low frequency and total power. After coronary angioplasty, regional wall motion and frequency domain measures of heart period variability were unchanged in Group A. In Group B the mean (+/- SD) summed segment score improved from 17.1 +/- 3.6 to 12.8 +/- 2.0 (p < 0.01), and mean low and high frequency power (logarithmic units) increased from 6.14 +/- 0.23 to 6.35 +/- 0.34 (p < 0.01) and from 5.43 +/- 0.32 to 5.68 +/- 0.52 (p < 0.01), respectively. Furthermore, low and high frequency power, lower at baseline in Group B than in the other two groups, were comparable in the three groups after coronary angioplasty. CONCLUSIONS: This study demonstrates that segmental left ventricular dysfunction is involved in determining sympathovagal imbalance in patients with one-vessel coronary artery disease; the reversal of left ventricular dysfunction by successful coronary angioplasty improves the heart period power spectrum. Thus, alterations in cardiac geometry influence the discharge of afferent sympathetic mechanoreceptors, contributing to the derangement in autonomic control of heart rate.

Afferent Pathways↗
PubMed1994

The GH receptor and signal transduction.

The primary structure of the growth hormone (GH) receptor in rabbits and humans determined by complementary DNA cloning revealed a single membrane-spanning protein of approximately 620 amino acids. A binding protein (bp) specific for GH has been identified in the serum of a number of species. In rabbits and man, a single 4.5-kb transcript has been identified that encodes the full-length receptor. In rats and mice, however, a smaller transcript produced by alternative splicing has been reported which is specific for the GHbp. Recently, the X-ray crystallographic structure of GH and its receptor have clearly shown the formation of an unusual homodimer, consisting of one molecule of GH and two molecules of hGHbp. Formation of the GH dimer is a necessary prerequisite for biological activity. The transcriptional activity of wild-type and mutant forms of GH receptor has been determined by co-transfecting the promoter of a GH-responsive gene, coupled to CAT along with the receptor cDNA. A 25-amino acid region near the transmembrane domain has been shown to be important for functional activity, although 8 amino acids (known as Box 1), rich in prolines, is essential. Alanine scanning mutagenesis has revealed that individual substitution of each residue is without effect, while the replacement of the last 2 or all 4 of the prolines abolishes activity. Finally, GH has been shown to induce rapid tyrosine phosphorylation of several proteins in cells expressing the receptor, one of which has recently been identified as the kinase JAK2 and another as MAP kinase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Abnormalities of cardiovascular baroreflex control in renal failure and cardiac insufficiency. Experimental study and brief critical review of the literature].

We attempted to determine the relevance and relative prevalence of autonomic dysfunction in 7 patients with end-stage renal disease (ESRD) but no heart disease, 8 patients with left ventricular dysfunction (LVD) with no renal disease and 8 patients with ESRD + LVD. In each group, the assessment of autonomic function and location of the lesion was performed by using the baroreflex sensitivity tests, based upon heart rate (ie Valsalva, deep breathing, lying to standing) to study the parasympathetic system as well as based upon blood arterial pressure (ie standing and sustained handgrip) to evaluate the sympathetic system. The same tests were performed in 7 healthy volunteers enrolled as control group. Separate studies were performed on the efferent parasympathetic arc (atropine test) and the efferent sympathetic arc (cold pressor test). There was evidence of parasympathetic damage in 100% of ESRD patients, in 87.5% of ESRD + LVD patients, and in 62.5% of LVD. Only 1 of ESRD patients showed defective response to atropine whereas the remaining had a normal response, suggesting an afferent lesion alone. No abnormalities were found in the response to cold pressor test, thereby suggesting a lack of involvement of the efferent sympathetic arc. The response to handgrip was higher in LVD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

[Effects of coronary angioplasty on heart rate variability explored in the domain of time and frequency in patients with one-vessel coronary disease].

BACKGROUND: Heart period variability is frequently reduced in patients with coronary artery disease. Although the mechanism for this reduction is still unclear, it seems to reflect alterations in cardiac autonomic control. In this study we have evaluated the relation between reversible segmental left ventricular dysfunction and time and frequency domain measures of heart period variability in patients with coronary artery disease. METHODS AND RESULTS: Echocardiographic segmental left ventricular wall motion and time and frequency domain measures of heart period variability were evaluated in 32 patients with one-vessel coronary artery disease before and 16-24 days after successful percutaneous transluminal coronary angioplasty (PTCA). At baseline examination 12 patients (Group A) had normal and 20 (Group B) abnormal regional wall motion. Prevalence of previous myocardial infarction was higher and mean angiographic ejection fraction lower in Group B than in Group A. At baseline, time domain measures were comparable between the 2 groups, while low frequency (LF) and high frequency (HF) power were lower in Group B than in Group A. After PTCA, in Group A regional wall motion and time and frequency domain measures of heart period variability were unchanged. In Group B summed segment score improved from 17.1 +/- 3.6 to 12.8 +/- 2.0 (p < 0.01) and a significant increase occurred in standard deviation of the average normal RR (NN) intervals for all 5-minute segments of a 24-hour recording (SDNN index), in root mean square successive difference (r-MSSD) and in the percentage of differences between adjacent NN intervals > 50 msec (pNN50). In this group also LF and HF power (logarithmic units) increased from 6.14 +/- 0.23 to 6.35 +/- 0.34 (p < 0.01) and from 5.43 +/- 0.32 to 5.68 +/- 0.52 (p < 0.01) respectively. There was no correlation between measures of heart period variability, summed segment score, and left ventricular ejection fraction. CONCLUSIONS: This study demonstrates that segmental left ventricular dysfunction is involved in determining sympathovagal imbalance in patients with one-vessel coronary artery disease; the reversal of left ventricular dysfunction by successful PTCA improves heart period variability. These findings support the hypothesis that alterations in cardiac geometry may influence the discharge of afferent sympathetic mechanoreceptors, thus contributing to the derangement in autonomic control of heart rate.

Aged↗
PubMed1993

[Coronary vasoconstriction induced by digoxin in normal subjects and in patients with coronary atherosclerosis].

This study evaluated the effects of digoxin infusion (0.014 mg/kg in 10 min i.v.) on large coronary arteries measured by quantitative digital angiography. Twenty-two patients (aged 47 +/- 12), divided in 3 groups were studied. The effects of digoxin infusion (after 10 and 20 min) and sublingual administration of isosorbide dinitrate were investigated in Group I (patients with angiographically normal coronary arteries, n = 9) and in Group II (patients with atherosclerotic coronary arteries, n = 8). In Group III (n = 5) to determine whether or not the effects of digoxin were mediated by activation of alpha-adrenergic receptors, coronary angiographies were performed after alpha-adrenoceptor blockade (phentolamine 0.11 mg/kg, i.v.). In Group I, 10 min after the end of digoxin infusion, cross-sectional area decreased from 7.7 +/- 4.1 mm2 to 6.0 +/- 2.2 mm2, and after 20 min to 5.6 +/- 2.6 mm2 (p < 0.05). Isosorbide dinitrate reverted digoxin-induced vasoconstriction as cross-sectional area increased to 8.5 +/- 3.4 mm2 (NS versus baseline). By 20 min after digoxin infusion heart rate was significantly reduced from 79 +/- 16 to 74 +/- 13 b/min (p < 0.01). Peripheral vascular resistances increased significantly 10 min after digoxin infusion (from 1396 +/- 693 to 1693 +/- 984 dyne*s*cm-5, p < 0.05), whereas cardiac output did not change. In Group II, minimal stenosis diameter decreased significantly 20 min after digoxin infusion from 1.6 +/- 0.5 mm to 1.4 +/- 0.5 mm (p < 0.05). Again, isosorbide dinitrate reverted digoxin-induced vasoconstriction as minimal stenosis diameter increased (NS versus control).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗