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P Papageorgiou

Publications and source records attributed to P Papageorgiou.

14 recordsLinked to original sources
PubMed1991

Intracellular free Ca2+ is elevated in hypertrophic aortic muscle from hypertensive rats.

Vessels from hypertensive animals have been shown to have increased medial thickness and also to exhibit increased sensitivity to agonists. We tested the hypothesis that changes in intracellular Ca2+ concentration [( Ca2+]i) may be associated with the growth response and the altered contractility of the aortic smooth muscle of modified coarctation-hypertensive rats. Freshly isolated single cells, loaded with fura-2, showed significantly higher [Ca2+]i both at rest and after depolarization compared with normal rat aortic cells. These cells also exhibited at rest a significant nuclear-cytoplasmic [Ca2+] gradient. Furthermore, the increased [Ca2+]i was associated with increased nuclear volumes, suggesting the presence of polyploid nuclei, as determined by ethidium dimer fluorescence imaging. Intact vascular rings from hypertrophic rat aortas, loaded with aequorin, also showed significantly higher [Ca2+]i at rest and after depolarization compared with normal rat aortas. In addition, the maximal force per cross-sectional area generated by the hypertrophic muscle was less than normal, consistent with a change in the contractile phenotype of the growing smooth muscle cells. This is the first report to directly indicate an increase in [Ca2+]i in hypertrophic vascular smooth muscle in hypertensive animals.

Aequorin↗
PubMed1991

Increased Ca2+ signaling after alpha-adrenoceptor activation in vascular hypertrophy.

In an effort to explain the increased sensitivity to agonists of hypertrophic vascular muscle, intracellular Ca2+ concentration ([Ca2+]i)-signaling mechanisms were studied in normal and hypertrophic rat aortas from normotensive and coarctation-hypertensive rats. Based on both fura 2 fluorescence and aequorin luminescence measurements, qualitatively different patterns of Ca2+ mobilization occur in normal and hypertrophic rat aortic muscle. Normal rat aortic muscle contracts to phenylephrine with little or no increase in [Ca2+]i, whereas the angiotensin II-induced contraction is accompanied by a marked [Ca2+]i transient. In contrast, hypertrophic rat aortic muscle shows a dramatic increase in Ca2+ signaling after phenylephrine stimulation. Moreover, both the amplitude of the angiotensin-induced [Ca2+]i transient and the contractile sensitivity to this agonist are decreased in the hypertrophic muscle. Our results strongly suggest that the amplitude of the [Ca2+]i transient after agonist stimulation determines the contractile sensitivity and that there is an altered coupling of the alpha-adrenoceptor in the hypertrophic vascular muscle.

Angiotensin II↗
PubMed1990

The nuclear-cytoplasmic [Ca2+] gradient in single mammalian vascular smooth muscle cells.

We studied the nuclear-cytoplasmic [Ca2+] gradient in single, freshly dispersed smooth muscle cells from the ferret portal vein, by means of fluorescence ratio imaging microscopy. Cells were loaded with the cell-permeant calcium indicator fura-2 AM. Caffeine and platelet-derived growth factor (PDGF) were used in order to mobilize Ca2+ from the sarcoplasmic reticulum. Basal levels of nuclear and cytoplasmic [Ca2+] were 299 +/- 51 nM and 141 +/- 23 nM respectively (n = 10, p less than 0.001). At 3 min after 10mM caffeine, nuclear [Ca2+] decreased to 117 +/- 13 nM (n = 10, p less than 0.001), cytoplasmic [Ca2+] also decreased to 75 +/- 11 nM (n = 10, p less than 0.001) and the nuclear-cytoplasmic difference was no longer significant (p greater than 0.05). Similarly, 300pM of PDGF also abolished the nuclear-cytoplasmic [Ca2+] gradient (n = 12, p greater than 0.1). We conclude that in single muscle cells from the ferret portal vein a perinuclear sarcoplasmic reticulum could be a factor that contributes to the high apparent nuclear Ca2+ levels either through a dynamic Ca2+ influx, or by a fura-2 signal in the sarcoplasmic reticulum masking the true nuclear [Ca2+].

Animals↗
PubMed1989

Pathophysiologic role of calcium in the development of vascular smooth muscle tone.

Recent information indicates that the intracellular ionized calcium concentration [Ca2+]i plays a regulatory role not only in determining the magnitude of vascular tone but also in regulating growth of vascular tissue. Studies on living vascular smooth muscle cells using the calcium indicator aequorin have revealed that the relation between [Ca2+]i and contraction of the vascular smooth muscle cell is complex. More than 1 intracellular kinase may be involved, leading to the coexistence of multiple excitation-contraction coupling pathways. However, it appears that all of these pathways may be calcium-dependent. It is not yet known whether the cause of human essential hypertension involves an elevated [Ca2+]i in the vascular smooth muscle cell. However, evidence is presented supporting the concept that a decreased [Ca2+]i in the hypertensive smooth muscle cell will lead to a decrease in vascular tone and total peripheral resistance, and possibly also antagonize the growth response of the vascular smooth muscle cell associated with the secondary effects of hypertension.

Animals↗
PubMed1988

Coronary distending pressure and delayed myocardial ischemia.

The role of blood pressure alterations in the delayed onset of myocardial ischemia following sympathetic stimulation was studied in seven anesthetized dogs. In the presence of coronary stenosis, stimulation of the left stellate ganglion produced significant increases in heart rate and mean aortic pressure, but not in mean coronary blood flow or intracoronary pressure. Following cessation of stimulation, heart rate and aortic pressure returned to control levels over a 1- to 2-minute period. During this time, there was a progressive coronary vasoconstriction, as indicated by a significant fall in coronary arterial flow and intracoronary pressure. When the hypertensive response to stellate stimulation was prevented by controlled exsanguination, the coronary vasoconstriction was not delayed but occurred during stimulation. In the second phase of experiments, the aorta was constricted so as to raise systemic pressure to the peak level achieved during stimulation. Elevation of systemic pressure consistently restored coronary arterial blood flow and intracoronary pressure to the control values. By contrast, induction of hypertension by restimulation of the stellate ganglion failed to reverse the delayed coronary vasoconstriction. We conclude that delayed myocardial ischemia results from the imbalance between coronary distending pressure and an alpha-adrenergically mediated vasoconstrictor activity that persists following cessation of sympathetic nervous system stimulation.

Animals↗
PubMed1984

Suppressor T cells and soluble suppressor factors in allergy: effect of immunotherapy.

Suppressor-cell activity of Concanavalin-A-stimulated lymphocytes was studied in allergic patients by inhibition of one-way mixed lymphocyte culture reactions before and after allergy immunotherapy. This activity was compared with twelve healthy controls. In preliminary experiments, six out of eight allergic patients had no detectable T suppressor activity. In the second prospective group, eight out of eleven patients had much reduced suppressor-cell activity before immunotherapy, and seven out of eleven patients had much reduced activity after immunotherapy. The data suggest that non-specific T suppressor-cell activity is reduced in allergic patients but immunotherapy does not restore such activity.

Adolescent↗
PubMed1982

Increased excretion of modified adenine nucleosides by children with adenosine deaminase deficiency.

We have identified seven adenine nucleosides in urines of untreated adenosine deaminase (ADA) deficient patients, four of which (adenosine, 2'-deoxyadenosine, 1-methyladenosine and N6-methyladenosine) have been previously identified in urines of normals and/or ADA deficient patients. We confirm that ADA deficient patients excrete markedly increased amounts of 2'-deoxyadenosine (582 +/- 363 versus normal of less than 0.1 nmoles/mg creatinine) and increased amounts of adenosine (29.4 +/- 5.7 versus normal of 4.12 +/- 1.0 nmoles/mg creatinine). We have found three modified adenine nucleosides previously undetected in human urine. These three compounds are 2'-O-methyladenosine, N6, 2'-O-dimethyladenosine and an as yet incompletely characterized modified adenine nucleoside, R-adenosine. Only ADA deficient patients excrete detectable amounts of 2'-O-methyladenosine (2.1 +/- 1.1 versus normal of less than 0.1 nmoles/ mg creatinine), whereas both normals and ADA deficient children excrete N6, 2'-O-dimethyladenosine and R-adenosine. However, ADA deficient patients do excrete increased amounts of R-adenosine (5.5 +/- 1.0 versus normal of 1.4 +/- 0.4 nmoles/mg creatinine).

Adenine Nucleotides↗
PubMed1982

Levamisole in chronic pyoderma.

Eleven patients, 8 females and 3 males, aged 17-53 years with chronic recurrent pyoderma (mean duration of 8.4 years) unresponsive to a variety of therapeutic modalities, were treated with oral levamisole 1 . 5-2 . 5 mg/kg/day (100-200 mg daily) for 2 consecutive days every week. Five out of eleven patients (3 males and 2 females) demonstrated one or more host defense abnormalities including impaired polymorphonuclear (PMN) chemotaxis, impaired bactericidal activity against Staphylococcus aureus, decreased in vitro lymphocyte response to Phytohaemagglutinin (PHA) and low serum IgM and IgA. Seven of eleven patients showed clinical improvement following levamisole administration for 4-11 months. Two showed complete clearance of skin lesions while on levamisole and for a year thereafter; three showed marked clearance of lesions during levamisole therapy but recurred with mild disease 6 months after termination of levamisole therapy; and two showed improvement of lesions during therapy but recurred immediately after levamisole discontinuation. Levamisole treatment was also associated with complete in vitro correction of PMN bactericidal abnormality, improvement of PMN chemotactic abnormality and augmentation of in vitro lymphocyte response to PHA. Correlation between in vitro potentiation of host defense mechanisms and clinical response was noted. Significant probable side-effects necessitating discontinuation of therapy included transient elevation of liver enzymes in 2 patients and extensive hemorrhagic skin rash in one.

Adolescent↗
PubMed1980

Plasma deoxyadenosine, adenosine, and erythrocyte deoxyATP are elevated at birth in an adenosine deaminase-deficient child.

We have determined concentrations of adenosine, deoxyadenosine, and deoxyATP (dATP) in cord blood from an infant prenatally diagnosed as ADA deficient. Plasma deoxyadenosine and adenosine were already elevated in cord blood (0.7 and 0.5 microM vs. normal of less than 0.07 microM). Elevation of plasma deoxyadenosine has not previously been documented in these children. Erythrocyte dATP content was also elevated at birth (215 nmol/ml packed erythrocytes vs. normal of 2.9). These elevated concentrations of adenosine, deoxyadenosine, and dATP are similar to those we observed in another older adenosine deaminase-deficient patient and may explain the impaired immune function and lymphopenia seen at birth.

Adenosine↗
PubMed1975

Complement receptor in synchronized cultures of human hematopoietic cell lines.

Three previously established human lymphoid cell lines (HLV-1, SWB-16A, and B-1) were synchronized by double thymidine block and the lymphocyte surface receptor for complement was studied by the EAC-rosetting technique during the cell cycle. It was found that the proportion of cells with EAC rosettes remained unchanged throughout the various stages, indicating that the presence of the complement receptor in cultured lymphoid cells is independent of the cell cycle.

Animals↗