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Biomedical subjects

E Lianos

Publications and source records attributed to E Lianos.

17 recordsLinked to original sources
PubMed2006

Cisplatin-based chemotherapy for merkel cell carcinoma of the skin.

PURPOSE: Merkel cell carcinoma (MCC), a rare tumor of the skin with aggressive behavior, is usually fatal when advanced disease is present. The role of chemotherapy (CT) in the treatment of patients with MCC is unclear. METHODS: Over 15 years, 9 patients with locally advanced or metastatic disease were treated with carboplatin (CBDCA) (300 mg/m(2) of AUC 5 on Day 1) and etoposide (VP-16) (100 mg/m(2) on Days 1-3) every 3 weeks. As second-line CT, cisplatin (CDDP) (60-100 mg/m(2)), ifosfamide (IFO) (3-5 g/m(2)) and epirubicin (EPI) (30-50 mg/m(2)) were utilized. RESULTS: Of the 3 patients who received adjuvant therapy, one achieved complete response after 108+ months with second-line chemotherapy and radiotherapy, despite a brief relapse; 2 patients remain disease-free after 84+ and 108+ months. Of the 6 patients with locally advanced or metastatic disease who were treated with first-line chemotherapy, one (16.6 percent) achieved a complete response and 3 (50 percent) achieved partial response, for an overall response rate of 66.6 percent. Two patients (one with complete and one with partial response) received subsequent radiotherapy, following which complete response was achieved. Of the 2 complete responders, one patient remains disease-free after 56+ months. The median overall survival from the time of initial diagnosis for the whole group was 56 months (range 15-114 months); the median overall survival from the initiation of chemotherapy was 18 months (range 6-108+). Local recurrences and soft tissue metastases responded better than visceral metastases. Patients with partial response and no response had rapid disease progression and fatality, despite second-line chemotherapy and/or radiotherapy. CONCLUSION: MCC appears to be chemosensitive but can progress rapidly with fatal outcomes. Although the rarity of these tumors precludes randomized trials, a common treatment plan should be utilized by those treating MCC. This may allow some conclusions regarding the optimum treatment of patients with MCC to be drawn in the future.

Aged↗
PubMed2001

Heme oxygenase isoform-specific expression and distribution in the rat kidney.

BACKGROUND: The heme oxygenase (HO) genes, HO-1 and HO-2, are the limiting steps in heme degradation and in the regulation of renal heme-dependent enzymes. Previously we reported that selective overexpression of renal HO-1 resulted in a decrease of microsomal heme and the cytochrome P450-dependent arachidonic acid metabolite, 20 HETE, a vasoconstrictor. The present study was undertaken to explore the relative expression and contribution of each of the HO isoforms to HO activity in the rat kidney. METHODS AND RESULTS. Renal HO activity increased above control levels after an injection of the inducers of HO activity, heme or SnCl2. Stannous Mesoporphyrin (SnMP), a nonselective inhibitor of HO, when used alone or in combination with heme or SnCl2, decreased HO activity. Heme alone and combined with SnCl2 decreased the levels of heme content by 13 and 35%, respectively. Western blot analysis showed that both SnCl2 and heme readily induced HO-1 protein, whereas HO-2 was constitutively expressed. Immunohistochemistry showed the distribution of the HO-1 isoform primarily in proximal convoluted tubules. Western blot analysis exhibited relatively higher levels of HO-1 in isolated proximal tubules and relatively higher HO-2 levels in the thick ascending limbs of the loop of Henle and preglomerular arterioles. In vivo administration of HO-1 and HO-2 antisense oligodeoxynucleotides further confirmed that HO-2, but not HO-1, contributed to the basal HO activity; however, following induction of HO with heme, antisense to HO-1, but not to HO-2, inhibited the induced levels of HO activity. CONCLUSION: These results suggest that HO-2 is constitutively expressed in the rat kidney mainly within tubular and arteriolar structures, and its activity may modulate physiological function under basal conditions. On the other hand, the basal levels of expression of HO-1 in the rat kidney are relatively low, and its contribution to HO activity and the regulation of hemoproteins such as cytochrome P450 become apparent only under pathophysiological conditions causing HO induction.

Animals↗
PubMed2001

Finasteride: a long-term follow-up in the treatment of recurrent hematuria associated with benign prostatic hyperplasia.

OBJECTIVES: To assess the effectiveness and long-term results after finasteride treatment of recurrent hematuria associated with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: The study comprised 80 patients, aged 62-86 (mean 74) years, of whom 50 received finasteride 5 mg once daily for 4 years and 30 were used as controls. Patients with malignancy, severe hepatic or renal failure and hematologic disorders were excluded. Patients were divided into 3 groups according to the severity of hematuria (minor, moderate, severe). All patients were followed up at 3, 12, 24 and 48 months. RESULTS: The follow-up ranged from 8 to 48 (mean 22) months in the finasteride group and 3-42 (mean 23) months in the control group. Hematuria recurrence rates were 6/50 (12%) and 23/30 (77%) in the finasteride and control groups, respectively. Surgical treatment was needed in 6 patients of the finasteride group and 19 of the control group. Patients with minor hematuria experienced no recurrence of symptoms in the finasteride group in contrast to 13 of 17 patients in the control group. For the patients with moderate hematuria, recurrence of symptoms was observed in 3 of 13 in the finasteride group and 3 of 5 in the control group. Three of six patients with severe hematuria had a recurrence of symptoms after finasteride treatment in contrast to 7 of 8 in the control group. CONCLUSION: Finasteride has proved to be a safe, well tolerable and effective medication in reducing or preventing recurrent hematuria related to BPH.

Aged↗
PubMed1999

TNF-alpha induces actin cytoskeleton reorganization in glomerular epithelial cells involving tyrosine phosphorylation of paxillin and focal adhesion kinase.

Glomerular permeability for macromolecules depends partially on proper attachment of the glomerular epithelial cells (GEC) to the glomerular basement membrane (GBM). The latter requires integrity of the actin cytoskeleton, which in turn is regulated by specific actin-associated proteins. Since several glomerulopathies characterized by heavy proteinuria are associated with increased glomerular tumor necrosis factor alpha (TNF-alpha) expression, we studied the interaction of TNF-alpha with the actin cytoskeleton of cultured rat GEC. Incubation of GEC with 10 ng/ml TNF-alpha for variable time periods ranging from 15 min to 24 hr demonstrated a marked accentuation and redistribution of actin microfilaments, as shown by direct fluorescence analysis and confocal laser scanning microscopy. Quantitative biochemical determination of the G/total-actin ratio confirmed the above observations. Indeed, this ratio was significantly reduced, indicating substantial polymerization of G-actin and formation of F-actin. Concurrently, TNF-alpha rapidly induced tyrosine phosphorylation of both paxillin and focal adhesion kinase, without affecting the expression levels of these two proteins. In addition, tyrosine phosphorylation of vinculin became evident, indicating involvement of this focal adhesion marker in the observed actin reorganization. Inhibition of tyrosine phosphorylation by genistein prevented the reorganization of the actin cytoskeleton by TNF-alpha. We conclude that TNF-alpha induces substantial reorganization of actin cytoskeleton and focal adhesions. These effects occur simultaneously, with a prompt TNF-alpha-induced tyrosine phosphorylation of paxillin and focal adhesion kinase, indicating that these proteins, known to regulate actin polymerization and formation of focal adhesions, may be directly involved in the mechanism controlling the observed actin redistribution. These findings suggest that the observed TNF-alpha-actin cytoskeleton interactions may relate to the pathogenesis of glomerulopathies with heavy proteinuria, in which increased glomerular expression of TNF-alpha is associated with disturbances in the attachment of podocytes to the GBM.

Actins↗
PubMed1991

Insulin stimulates fatty acid acylation of adipocyte proteins.

Isolated rat adipocytes were incubated with [3H]palmitate in the presence or absence of insulin. Insulin caused marked (20-fold), rapid (T1/2 approximately 15 min), and concentration-dependent labeling of an 80 kilodalton protein. The insulin concentration producing half-maximal labeling was 0.4 ng/ml. The label was removed from the protein by treatment with hydroxylamine indicating the fatty acid was linked to the protein via an oxyester bond. Label removed from the protein co-eluted with palmitate standard by high-performance liquid chromatography. In summary, adipocyte proteins are subject to acylation by exogenous long-chain fatty acids and this process is stimulated by insulin.

Acylation↗
PubMed1991

Quinine-induced immune thrombocytopenia associated with hemolytic uremic syndrome: a new clinical entity.

Three patients are described who developed severe thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure after ingestion of quinine. In one patient, the same clinical findings recurred several months later after another exposure to quinine. Serum from one patient contained quinine-dependent IgG antibodies reactive with the platelet glycoprotein (GP) Ib/IX complex. In the second and third cases, serum contained IgG and IgM antibodies reactive with both the GP Ib/IX and IIb/IIIa complexes in the presence of quinine. Quinine appears to have induced both immune thrombocytopenia and the hemolytic uremic syndrome (HUS) in these individuals. Findings made in these cases may have implications for the pathogenesis of some forms of HUS.

Acute-Phase Reaction↗
PubMed1990

Influence of prostaglandins on papillary blood flow and pressure-natriuretic response.

The present study examined whether renal prostaglandins influence the pressure-natriuretic response by altering medullary hemodynamics or renal interstitial pressure. The diuretic and natriuretic responses to changes in renal perfusion pressure were compared in control rats (n = 15) and in rats receiving either meclofenamate (2 mg/kg, n = 9) or indomethacin (2 mg/kg, n = 4). In control rats, urine flow and sodium excretion increased from 10 +/- 2 to 118 +/- 10 microliters/min/g kidney wt and from 1.8 +/- 0.3 to 21.0 +/- 1.5 mueq/min/g kidney wt, respectively, when renal perfusion pressure was increased from 109 to 167 mm Hg. Urinary excretion of prostaglandin E2 and thromboxane B2 increased significantly by 152% and 190%, respectively. Meclofenamate lowered thromboxane B2 and prostaglandin E2 excretion and prevented the increase in eicosanoid excretion produced by elevations in perfusion pressure. The pressure-diuretic and pressure-natriuretic responses of rats given meclofenamate or indomethacin were approximately half of those observed in the control rats. Papillary blood flow increased 21% and renal interstitial pressure rose from 5.0 +/- 0.7 to 8.2 +/- 0.7 mm Hg in control rats when pressure was elevated from 100 to 150 mm Hg. Meclofenamate and indomethacin lowered papillary blood flow and renal interstitial pressure and blunted the increases in these values produced by elevations in perfusion pressure. These results support the view that renal prostaglandins modulate the pressure-natriuresis relation by altering renal medullary hemodynamics and suggest that an intact renal prostaglandin system is necessary for the full expression of the medullary hemodynamic and natriuretic responses to increases in renal perfusion pressure.

Animals↗
PubMed1985

Peritoneal permeability in the rat: modulation by microfilament-active agents.

A model of peritoneal dialysis in the rat was used to determine the effects of cytochalasins on ultrastructure and peritoneal permeability to molecules of varying molecular weight. The permeability to urea, inulin, and plasma albumin were determined after intraperitoneal administration of cytochalasin B (2 to 10 X 10(-6) M) and cytochalasins D and E (2 X 10(-6) M). Cytochalasin B (20 X 10(-6) M) increased the permeability to inulin, urea, and albumin by 30, 60, and 150%, respectively. These effects were, to a large degree, reversible. Cytochalasins D and E produced greater increments in permeability for all molecules; this increase was only partially reversible. Ultrastructure analysis by scanning electron microscopy revealed extensive development of membrane protuberances (zeiotic knobs) on mesothelial cells exposed to cytochalasin B. A return to a normal apical cell surface was apparent although incomplete at 24 hr. Tight junctions were not grossly altered and major changes in intramembranous junctional strands were not observed. The major effect of cytochalasins on the cell surface may be responsible for the increased permeability to urea, predominately a transcellular probe. Inulin, which follows a paracellular route, was less affected. Altered protein permeability may be due to the action of cytochalasin on the exposed capillary endothelium in subdiaphragmatic areas where the mesothelium is discontinuous.

Animals↗
PubMed1983

Arachidonate metabolites and the control of glomerular function.

The glomerulus is a dynamic structure capable of regulating the glomerular filtration rate (GFR) by mesangial contraction, thereby decreasing Kf. The mesangium contracts in response to angiotensin II (AII) and arginine vasopressin (AVP), both of which are potent stimuli of vasodilatory prostaglandin (PG) production. We studied interactions among these opposing factors in glomeruli. Normal rat glomeruli synthesized PGF2 alpha greater than PGE2 greater than 6-keto-PGF1 alpha = thromboxane (Tx) B2. Rat glomerular epithelial and mesangial cells, although capable of producing these four cyclooxy-genase end products, responded to AVP and AII stimulation with a preferential increase of PGE2, which suggests an intraglomerular feedback system between constrictor and dilator factors. Whole glomeruli, when incubated in AII, decreased in size, with a maximum decrement of surface area at 10(-10) M AII. In these glomerular contraction studies, preincubation with either arachidonate or PGE2 decreased the contractile response to AII, whereas PG inhibition enhanced the glomerular contractile response. Stable endoperoxide analogs also contracted glomeruli. In the acute phase of nephrotoxic serum nephritis (NSN) there were marked increments in glomerular production of TxA2, which correlated temporally with decrements of GFR and filtration fraction. Inhibition of TxA2 synthesis normalized GFR and filtration fraction 1-3 h after induction of NSN. These studies suggest not only an important physiological feedback role of vasodilatory PGs, as modulators of AII-induced glomerular contraction, but also a direct mesangial contractile effect of the arachidonate metabolite TxA2.

Angiotensin II↗
PubMed1982

Uterine and peripheral blood concentrations of vasodilator prostaglandins in conscious pregnant rabbits.

The concentrations of prostaglandin E2 (PGE2) and prostacyclin (PGI2) were estimated in blood obtained from the uterine venous effluent and a peripheral artery of conscious pregnant and nonpregnant rabbits. The blood was analyzed both with a superfusion bioassay and radioimmunoassays. PGE2, but not PGI2, was detected in a very high concentration in the uterine venous effluent of the pregnant rabbit. The peripheral blood of pregnant animals also revealed increased levels of only PGE2. The results of both assay techniques correlated closely. These studies suggest that the uteroplacental unit is the source of the increased peripheral level of the potent vasodilator PGE2. In contrast, these data fail to support the notion that PGI2 is the primary systemic-acting vasodepressor prostaglandin in rabbit pregnancy.

Animals↗
PubMed1982

Effect of protamine on the permeability and structure of rat peritoneum.

The effect of protamine, a polycationic protein, on the mesothelial permeability and ultrastructure was evaluated in a rat model of peritoneal dialysis. The peritoneal permeability to urea and inulin were measured after the intraperitoneal instillation of protamine sulfate in varying concentrations. A functional correlation was made with the ultrastructure of omentum. Protamine concentrations between 5 and 30 micrograms/ml decreased the permeability to inulin without significantly altering that of urea. At concentrations from 30 to 75 micrograms/ml, protamine increased permeability to urea by 50% and to inulin by 20%. Mesothelial cells revealed a loss of microvilli and minor degrees of disorganization of submembranous, cytoplasmic microfilaments without significant changes in the intramembranous structure of occluding junctions. Effects were partially reversible. At a concentration of 100 micrograms/ml, there was an irreversible doubling in permeability to inulin without a comparable effect on permeability to urea associated with the disruption of occluding junctions in focal areas. This complex response to protamine suggests at least two transperitoneal diffusion pathways, transcellular and paracellular. The mesothelial cell occluding junctions may be a diffusion barrier in the latter pathway.

Animals↗
PubMed1979

Hemodialysis for methanol intoxication.

A patient with toxic levels of methanol was hemodialyzed while receiving an ethanol infusion. It was demonstrated that during the dialysis significant quantities of both ethanol (17.70 gms) and methanol (26.69 gms) were extracted. Also, it was shown that the ethanol did not competetively inhibit the extraction of the methanol. Since ethanol is removed in significant quantities during dialysis, one should increase its infusion rate during hemodialysis and decrease the rate when the patient is not being dialyzed. This would achieve adequate and constant blood levels of ethanol and would satisfactorily inhibit the metabolism of methanol by the liver.

Aged↗
PubMedDate not supplied

Dermatomyositis associated with breast cancer.

An increased risk of underlying malignancy has been found in patients with dermatomyositis (DM). The risk is increased even in patients with DM aged 45 or younger and remains high for many years after diagnosis. Breast carcinoma does not represent the most common solid tumor associated with this autoimmune disorder. In the present report, two new cases of DM associated with breast cancer are described, together with an extensive literature review.

Adult↗
PubMedDate not supplied

Glomerular NO synthase activity in mesangial cell immune injury.

Ex vivo synthesis of nitrite (NO2-) by nephritic glomeruli provides evidence of induction of nitric oxide (NO) in glomerulonephritis (GN). In macrophage-associated GN, the major source is infiltrating macrophages. As induction of NO synthesis has now been shown in cultured mesangial cells, we have examined whether in vivo mesangial proliferation is a source of NO2-. Mesangial proliferative GN was induced by intravenous anti-Thy1.1 (monoclonal antibody ER4). Isolated glomeruli were assayed for NO2- synthesis and macrophage infiltration on day 4 (mesangiolytic phase) and on day 7 (mesangial proliferation). On day 4, but not on day 7, basal NO2- was increased (8.3 +/- 1.8, controls 0.7 +/- 0.1 nmol/2,000 glomeruli/48 h; p = 0.05) and there was macrophage infiltration (60 +/- 15; controls 14 macrophages/glomerulus). At both times NO2- was elevated by exogenous IL1 or LPS, more significantly on day 4 than on day 7. Thus, mesangial proliferative lesions are not a source of basal NO2-, and macrophages are the most likely source. However, NO2- can be induced in mesangial proliferative glomeruli by exogenous stimuli, findings similar to those reported in cultured mesangial cells. Irradiation experiments in normal rats show that stimulated NO2- synthesis is inhibited by macrophage depletion. Therefore in neither normal nor proliferative glomeruli is there evidence for mesangial cell production of NO2-.

Amino Acid Oxidoreductases↗