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A Pagano

Publications and source records attributed to A Pagano.

At least 37 records · Page 2Linked to original sources
PubMed2000

The non-competitive antagonists 2-methyl-6-(phenylethynyl)pyridine and 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester interact with overlapping binding pockets in the transmembrane region of group I metabotropic glutamate receptors.

We have investigated the mechanism of inhibition and site of action of the novel human metabotropic glutamate receptor 5 (hmGluR5) antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP), which is structurally unrelated to classical metabotropic glutamate receptor (mGluR) ligands. Schild analysis indicated that MPEP acts in a non-competitive manner. MPEP also inhibited to a large extent constitutive receptor activity in cells transiently overexpressing rat mGluR5, suggesting that MPEP acts as an inverse agonist. To investigate the molecular determinants that govern selective ligand binding, a mutagenesis study was performed using chimeras and single amino acid substitutions of hmGluR1 and hmGluR5. The mutants were tested for binding of the novel mGluR5 radioligand [(3)H]2-methyl-6-(3-methoxyphenyl)ethynyl pyridine (M-MPEP), a close analog of MPEP. Replacement of Ala-810 in transmembrane (TM) VII or Pro-655 and Ser-658 in TMIII with the homologous residues of hmGluR1 abolished radioligand binding. In contrast, the reciprocal hmGluR1 mutant bearing these three residues of hmGluR5 showed high affinity for [(3)H]M-MPEP. Radioligand binding to these mutants was also inhibited by 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt), a structurally unrelated non-competitive mGluR1 antagonist previously shown to interact with residues Thr-815 and Ala-818 in TMVII of hmGluR1. These results indicate that MPEP and CPCCOEt bind to overlapping binding pockets in the TM region of group I mGluRs but interact with different non-conserved residues.

Amino Acid Sequence↗
PubMed2000

Pulsed intravenous high-dose dexamethasone in adults with chronic idiopathic thrombocytopenic purpura.

The role of pulsed high-dose dexamethasone (DXM) in the treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP) is still uncertain. Following an early report in which it was described as an effective and well-tolerated treatment with a sustained platelet response in 100% of cases, a number of subsequent studies have failed to confirm such favorable results. As all these studies were conducted on small numbers of patients, we investigated further the effectiveness and side effects of this therapeutic modality in a larger cohort. Thirty-two patients with chronic ITP were scheduled to receive six monthly courses of intravenous DXM at the dose of 40 mg/day for 4 consecutive days. All patients had ITP that had been resistant to between two and five different therapeutic regimens, including 9 patients who had already failed splenectomy. All patients had to be seen 2 weeks after each cycle to asses their response as well as secondary effects. Three patients failed to respond and clinically required other therapy. Thirteen patients (41%) had a partial (platelet count between 50 and 100 x 10(9)/liter) or complete (platelet count >100 x 10(9)/liter) response to treatment, responses being mostly transient. Responses were observed early during the course of treatment, usually right after the first cycle of DXM. There were no late responses. Side effects were mild and did not require discontinuation of treatment. No clinical or laboratory parameter was found to predict treatment outcome. We conclude that high-dose DXM has a limited effect in patients with chronic ITP. Novel approaches and controlled multicenter trials may help identify new therapeutic strategies for this disease.

Adult↗
PubMed2000

Intravascular ultrasound insights into plaque composition.

UNLABELLED: Previous studies correlating histomorphology with 20-30 MHz-derived intravascular ultrasound (IVUS) images showed that IVUS provides to some extent qualitative information on plaque composition. IVUS imaging proved to define calcifications with high sensitivity and specificity but was found to be less accurate in the assessment of soft components. Nevertheless previous studies on atherosclerotic plaque characterization were limited by use of low-frequency transducers that did not define accurately soft components. Our goal was to test the effectiveness of high frequency IVUS transducers in the identification of lipid/necrotic pools in atherosclerotic plaques. METHODS: Forty MHz transducers were used for in vitro IVUS assessment of 12 arterial segments (10 coronary arteries and 2 carotid arteries dissected from 5 different autopsy cases). IVUS acquisition was performed at a 0.5 mm/s speed after ligature of the branching points to generate a closed system. Lipid necrotic areas were defined by IVUS as large echolucent intraplaque areas surrounded by tissue with higher echodensity. To obtain histopathologic sections corresponding to IVUS cross sections, vessels were divided into consecutive 3 mm-long segments using the most distal recorded IVUS image as the starting reference. Then, samples were fixed with 10% buffered formalin, processed for histopathologic study, serially cut, and stained with the Movat penthacrome method. RESULTS: One hundred twenty-two sections were analyzed. Lipid pools were observed by histology in 30 cross sections (25%). IVUS revealed the presence of lipid pools in 19 of 122 cross sections with a sensitivity and specificity of 67% and 94%, respectively. CONCLUSIONS: High frequency transducers accurately identify lipid/necrotic pools and open new perspectives on future IVUS characterization of atherosclerotic plaques.

Arteriosclerosis↗
PubMed2000

Variations in call and morphology in male water frogs: taxonomic and evolutionary implications.

In Anurans, the specific mate recognition system (SMRS), which contributes to prezygotic isolation, is mainly based on morphological and call features. This is why such criteria are used by zoologists for taxonomic identification. In hybridogenetic water frogs (Rana ridibunda, R. lessonae, R. perezi, R. kl. grafi and R. kl. esculenta), hybridization opens up the question of the efficiency of these criteria for taxon identification and of the specific recognition system in this context. Variation in both morphological and call features revealed both significant mean differences among taxa but also large overlapping among individuals belonging to different taxa. Thus, using call or morphometrical features in order to identify water frogs may be hazardous. Moreover, species differ poorly in their specific mate recognition system, facilitating hybridization events, and therefore suggesting that postzygotic mechanisms may be prevalent over prezygotic mechanisms.

Animals↗
PubMed2000

COPI-coated ER-to-Golgi transport complexes segregate from COPII in close proximity to ER exit sites.

Transport of proteins between the endoplasmic reticulum and Golgi apparatus is mediated by two distinct membrane coat complexes, COPI and COPII. Genetic, biochemical and morphological data have accumulated into a model which suggests a sequential mode of action with COPII mediating the selection of cargo and formation of transport vesicles at the ER membrane for ER-to-Golgi transport and COPI mediating recycling of the transport machinery from post-ER membranes. To test this transport model directly in vivo, and to study the precise temporal sequence of COPI and COPII action in ER-to-Golgi transport, we have used time lapse microscopy of living cells to visualise simultaneously the dynamics of COPII and COPI, as well as COPII and GFP tagged secretory markers in living cells. The majority of COPII labelling appears tightly associated with ER membranes that move only within a limited area (less than 2 microm). Secretory cargo segregates from these sites and is then transported to the Golgi apparatus without any apparent association with COPII. COPI-coated transport complexes are seen to form adjacent to the COPII sites on the ER before segregating and moving directionally towards the Golgi apparatus. COPII is not present on these transport complexes and remains associated with the ER. These data demonstrate for the first time directly in vivo that ER-to-Golgi transport is organised in two steps characterised by a sequential mode of action of COPII and COPI.

Animals↗
PubMed2000

The role of vitamin B12 in fasting hyperhomocysteinemia and its interaction with the homozygous C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. A case-control study of patients with early-onset thrombotic events.

Total fasting plasma homocysteine (tHcy), homozygosity for the C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene and for the A2756G mutation of the methionine synthase (MS) gene, vitamin B12 and folate plasma levels were evaluated in 170 consecutive patients (89 M, 81 F; mean age 41 +/- 12 yrs) with documented early-onset thrombosis (89 venous, 69 arterial, 12 both; mean age at first episode 36 +/- 11 yrs), and in 182 age- and sex-matched healthy control subjects. Moderate hyperhomocysteinemia (HHcy, tHcy >19.5 microM in men and >15 microM in women) was detected in 45 patients (26.5%) and in 18 controls (9.9%, Mantel-Haenszel OR and 95% C.I. after stratification for arterial or venous thrombosis: 3.25, 1.78-5.91). The 677TT MTHFR genotype was not significantly more prevalent in patients (27.6%) than in controls (21.4%, RR = 1.42: 0.84-2.41), and markedly contributed to HHcy (Mantel-Haenszel RR after stratification for case/control status: 8.29, 4.61-14.9). The 2756GG MS genotype, observed in 4 patients (2.4%) and 8 controls (4.4%), was not associated to HHcy. tHcy was negatively correlated to folate and vitamin B12 levels, with better correlation found in subjects with the 677TT mutation (r = -0.42 and -0.25) than with the 677CC or CT MTHFR genotype (r = 0).37 and -0.11). However, folate was similar in patients and controls and vitamin B12 was higher in patients (460 +/- 206 vs. 408 +/-185 pg/ml, p = 0.011). In a generalized linear model, 44% of the variation in tHcy levels was explained by folate and vitamin B12 levels, the MTHFR genotype, gender, and by the interaction of the MTHFR genotype with folate (p < or =0.028); the interactions of vitamin B12 with the MTHFR genotype, gender and patient/control status also significantly contributed to the variation in tHcy levels (p < or =0.028). A 4-week administration of 5-methyltetrahydrofolate (15 mg/day) markedly lowered plasma tHcy in 24 patients with MTHFR 677TT genotype, but the response to treatment correlated with vitamin B,2 levels (p = 0.023). Subjects carrying the MTHFR 677TT genotype have higher folate and vitamin B12 requirements irrespective of the A2756G polymorphism of the MS gene. Yet unidentified abnormalities of MS or of any of the enzymes participating in the synthesis of methylated vitamin B12 may play an important role in the phenotypic expression of moderate hyperhomocysteinemia.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2000

[Autonomic neuropathy in a diabetic population. Validity of cardiovascular tests and correlations with the complications].

The disfunction of the autonomic system nervous is a frequent finding in diabetes mellitus. Among objective tests proposed for its diagnosis, those assessing cardiovascular reflexes (cardiovascular tests: CVTs) explore the autonomic functionality by means of a group of standardized manoeuvres of relatively easy execution that study the baroreceptorial reflex arc. In our study, CVTs were performed in a population of 207 diabetic patients with no symptoms of autonomic neuropathy. A computerized automatic system (Cardionomic) was utilized. CTVs included: Deep Breathing, Lying to Standing, Valsalva Manoeuvre, Orthostatic Hypotension, Standing to Lying and Cough Test. Diabetic patients were broken down in groups according to: a) age, b) HbA1c levels, c) disease duration. We have then compared the presence of diabetic complications between the group of diabetics positive for cardiovascular disautonomia (CVD+) with another group of diabetics who were negative for cardiovascular disautonomia (DCV-). Our results show a remarkable correlation between autonomic neuropathy and patients age, HbA1c levels and disease duration. Also they show a strong positive correlation between CDV+ and the severity of arteriopathy. We conclude that autonomic neuropathy may play an important role in the pathogenesis of diabetic arteriopathy.

Adult↗
PubMed1999

Sec24 proteins and sorting at the endoplasmic reticulum.

COPII proteins are necessary to generate secretory vesicles at the endoplasmic reticulum. In yeast, the Sec24p protein is the only COPII component in which two close orthologues have been identified. By using gene knock-out in yeast, we found that the absence of one of these Sec24 orthologues resulted in a selective secretion defect for a subset of proteins released into the medium. Data base searches revealed the existence of an entire family of Sec24-related proteins in humans, worms, flies, and plants. We identified and cloned two new human cDNAs encoding proteins homologous to yeast Sec24p, in addition to two human cDNAs already present within the data bases. The entire Sec24 family identified to date is characterized by clusters of highly conserved residues within the 2/3 carboxyl-terminal domain of all the proteins and a divergent amino terminus domain. Human (h) Sec24 orthologues co-immunoprecipitate with hSec23Ap and migrate as a complex by size exclusion chromatography. Immunofluorescence microscopy confirmed that these proteins co-localize with hSec23p and hSec13p. Together, our data suggest that in addition to its role in the shaping up of the vesicle, the Sec23-24p complex may be implicated in cargo selection and concentration.

Amino Acid Sequence↗
PubMed1999

The heteromeric GABA-B receptor recognizes G-protein alpha subunit C-termini.

The recently cloned GABA-B receptors are related to the metabotropic glutamate receptors (mGlu receptors), the Ca2+-sensing receptor and one group of vomeronasal receptors. The GABA-B receptors likely function in a heterodimeric form, constituted of GABA-BR1 and GABA-BR2. This novel feature in the G-protein coupled receptors (GPCRs) structure raises questions as to the mechanism of recognition of G-proteins by such receptors. In the present study we show that the GABA-BR1 and BR2 subunits form a functional receptor that recognizes the extreme C-termini of the G alpha i and G alpha o proteins when expressed in HEK293 cells. Indeed, heteromeric GABA-BR1/BR2 receptors do not activate PLC when co-expressed with G alpha q, but do so when co-expressed with the chimeric G alpha qi5 or G alpha qo5 subunits, the G alpha q subunit in which the 5 C-terminal residues are those of G alpha i or G alpha o, respectively. Interestingly, the heteromeric GABA-B receptor did not activate the chimeric G alpha qz5 subunit that contains the 5 C-terminal residues of G alpha z. Among the three residues that are distinct between G alpha qo5 and G alpha qz5 (at position -5, -4 and -1), the amino acid residue at position -4 of G alpha o proteins is critical for specifying the coupling selectivity with the receptor and residue -5 influences the coupling efficacy. Interestingly, these findings correspond to data obtained with the mGluR2 receptor, a distant relative of GABA-B proteins. This shows that the same molecular determinants of the G-protein alpha-subunits are involved in the specific recognition of both the heteromeric GABA-B receptors and the other GPCRs.

Amino Acid Sequence↗
PubMed1999

Recombinant human granulocyte-macrophage colony-stimulating factor plus erythropoietin for the treatment of cytopenias in patients with myelodysplastic syndromes.

In vitro studies have indicated that granulocyte-macrophage colony-stimulating factor (GM-CSF) synergizes with erythropoietin (EPO) for the production of erythroid precursors in patients with myelodysplastic syndrome (MDS). We performed a clinical trial to evaluate whether the combination of these growth factors was effective in relieving the cytopenias associated with MDS. 31 anaemic patients with low and intermediate-risk primary MDS were enrolled in a 12-week study. Therapy was initiated with GM-CSF at 1 microgram/kg/d.s.c., and then adjusted to either normalize or double the absolute neutrophil count. EPO was given subcutaneously on alternate days starting from day 2. The EPO dose was initiated at 150 U/kg and increased to 300 U/kg if after 6 weeks there was no or suboptimal erythroid response. 26 patients completed the study treatment. All evaluable cases had a neutrophil response. Clinically significant erythroid responses with increases of haemoglobin levels of at least 1 g/dl and/or reduction of transfusion needs were seen in 9/26 (34.6%), five patients improving their response after dose escalation of EPO. Treatment had no apparent effect on mean platelet counts, a single case displaying a trilineage response. An elevated bone marrow erythroid infiltration and low concentrations of circulating tumour necrosis factor-alpha were the only predictors of haemoglobin response both in univariate and in multivariate analysis. We conclude that the combination GM-CSF + EPO can abrogate neutropenia and substantially relieve transfusion requirements in a large proportion of patients with low and intermediate risk MDS. However, in vivo synergy between these growth factors for the production of erythroid precursors is not supported by our data.

Adult↗
PubMed1998

In vitro reconstitution of the recombinant photosystem II light-harvesting complex CP24 and its spectroscopic characterization.

The light-harvesting chlorophyll a/b protein CP24, a minor subunit of the photosystem II antenna system, is a major violaxanthin-binding protein involved in the regulation of excited state concentration of chlorophyll a. This subunit is poorly characterized due to the difficulty in isolation and instability during purification procedures. We have used an alternative approach in order to gain information on the properties of this protein; the Lhcb6 cDNA has been overexpressed in bacteria in order to obtain the CP24 apoprotein, which was then reconstituted in vitro with xanthophylls, chlorophyll a, and chlorophyll b, yielding a pigment-protein complex with properties essentially identical to the native protein extracted from maize thylakoids. Although all carotenoids were supplied during refolding, the recombinant holoprotein exhibited high selectivity in xanthophyll binding by coordinating violaxanthin and lutein but not neoxanthin or beta-carotene. Each monomer bound a total of 10 chlorophyll a plus chlorophyll b and two xanthophyll molecules. Moreover, the protein could be refolded in the presence of different chlorophyll a to chlorophyll b ratios for yielding a family of recombinant proteins with different chlorophyll a/b ratios but still binding the same total number of porphyrins. A peculiar feature of CP24 was its refolding capability in the absence of lutein, contrary to the case of other homologous proteins, thus showing higher plasticity in xanthophyll binding. These characteristics of CP24 are discussed with respect to its role in binding zeaxanthin in high light stress conditions. The spectroscopic analysis of a recombinant CP24 complex binding eight chlorophyll b molecules and a single chlorophyll a molecule by Gaussian deconvolution allowed the identification of four subbands peaking at wavelengths of 638, 645, 653, and 659 nm, which have an increased amplitude with respect to the native complex and therefore identify the chlorophyll b absorption in the antenna protein environment. Gaussian subbands at wavelengths 666, 673, 679, and 686 nm are depleted in the high chlorophyll b complex, thus suggesting they derive from chlorophyll a.

Amino Acid Sequence↗
PubMed1998

Higher plants light harvesting proteins. Structure and function as revealed by mutation analysis of either protein or chromophore moieties.

Mutation analysis of higher plants light harvesting proteins has been prevented for a long time by the lack of a suitable expression system providing chromophores essential for the folding of these membrane-intrinsic pigment-protein complexes. Early work on in vitro reconstitution of the major light harvesting complex of photosystem II (LHCII) indicated an alternative way to mutation analysis of these proteins. A new procedure for in vitro refolding of the four light harvesting complexes of photosystem II, namely CP24, CP29, CP26 and LHCII yields recombinant pigment-proteins indistinguishable from the native proteins isolated from leaves. This method allows both the performing of single point mutations on protein sequence and the exchange of the chromophores bound to the protein scaffold. We review here recent results obtained by this method on the pigment-binding properties, on the chlorophyll-binding residues, on the identification of proton-binding sites and on the role of xanthophylls in the regulation of light harvesting function.

Amino Acid Sequence↗
PubMed1998

The prognostic value of soluble interleukin-6 receptor in patients with multiple myeloma.

BACKGROUND: The effect of interleukin-6 (IL-6), the major growth factor for myeloma cells, may be enhanced by soluble IL-6 receptor (sIL-6R). Therefore, the current study investigated the clinical significance of serum sIL-6R in patients with multiple myeloma (MM). METHODS: Serum levels of sIL-6R were determined by enzyme-linked immunoassay in 55 normal controls, 81 individuals with monoclonal gammopathy of undetermined significance (MGUS), and 164 patients with MM in various phases of the disease. RESULTS: sIL-6R concentrations were higher in MM patients (162.0 +/- 134.6 ng/mL) than in individuals with MGUS (58.9 +/- 36.7 ng/mL) or in controls (45.6 +/- 22.3 ng/mL) (P = 0.0000). sIL-6R was not found to have a significant linear correlation with any other parameter, including IL-6, beta2-microglobulin (beta2-m), and neopterin, either in newly diagnosed cases or during the course of the disease. In addition, there were no statistically significant differences in sIL-6R concentrations between the clinical stages at the time of diagnosis. In univariate logistic regression analysis sIL-6R was a significant but weak prognostic indicator (P = 0.000000). Kaplan-Meier analysis showed that elevated levels of sIL-6R were associated with shorter survival (P = 0.00282). Patients also were stratified according to their serum beta2-m and sIL-6R levels. Patients with low levels of both parameters had a clear survival benefit over the other groups (P = 0.000000). CONCLUSIONS: The correlation between sIL-6R levels and survival is significant but weak, making it unlikely to be of much value in predicting the outcome of patients with MM alone. The results of the current study support the role of sIL-6R levels in improving the prognostic value of beta2-m and in discriminating patients with MM from individuals with MGUS.

Adult↗
PubMed1998

Hepatitis C virus infection and acute or chronic glomerulonephritis: an epidemiological and clinical appraisal.

BACKGROUND: The relationship between hepatitis C virus (HCV) infection and acute or chronic glomerulonephritis (GN) is not well understood. METHODS: Two hundred and eighty-four patients with biopsy-proven GN and other renal diseases were studied in a multicentre survey performed during the period 1992-1995. Several clinical parameters were collected for each patient at the time of renal biopsy. We made a multivariate analysis by logistic regression model to evaluate the independent association of clinical and histological patient characteristics with HCV infection, as detected by anti-HCV antibody testing. In addition, three patients with HCV-related liver disease, membranous nephropathy, and proteinuria in the nephrotic range received therapy with interferon-alpha in standard doses. RESULTS: The prevalence of anti-HCV positivity was 13% (38/284). The frequency of anti-HCV positivity ranged between 0 and 100% in the different types of renal diseases, the difference was statistically significant (P = 0.0001). The anti-HCV rate was significantly higher in patients with cryoglobulinaemic membranoproliferative and mesangioproliferative GN than among the other individuals (14/14 (100%) vs 24/270 (9%), P = 0.0002). Our multivariate analysis by logistic regression model showed that age (P = 0.0017) and type of renal diseases (P = 0.0007) were independently and significantly associated with anti-HCV antibody. At the completion of treatment with interferon-alpha, 67% (2/3) of patients with membranous nephropathy had lowering of hepatic enzyme levels into the normal range whereas 100% (3/3) of these did not show significant reduction of proteinuria. CONCLUSIONS: We observed strong association between HCV infection and cryoglobulinaemic GN. Age and type of renal disease were important independent predictors of anti-HCV positivity in our cohort of patients. Three anti-HCV-positive patients with membranous nephropathy did not show significant remission of nephrotic proteinuria after treatment with interferon-alpha. Our data do not appear to support an association between HCV and non-cryoglobulinaemic GN. Further epidemiological surveys, experimental studies and clinical trials are warranted to fully elucidate the role of HCV in non-cryoglobulinaemic GN.

Acute Disease↗
PubMed1998

Role of human leukocyte interferon-alpha in the treatment of patients with polycythemia vera.

Eighteen patients with polycythemia vera who were less than 60 years old received human leukocyte interferon-alpha subcutaneously at a starting dose of 3 MU three times a week. The interferon dose was escalated to 6 MU three times a week if it was well tolerated and disease was not controlled after 3 months of treatment at the lower dose. Hematologic response was defined as complete if the hematocrit was maintained at less than 45% in the absence of phlebotomy and partial if the hematocrit was kept at 45% to 50%, associated with a 50% or greater reduction of phlebotomy requirements; no response was defined as a response less than a partial response. Complete disease control was achieved in 11 patients, with partial control in a further six cases. One patient failed to respond. Median duration of response was 16 months (range 5 to 43 months), with 15 patients still under treatment. Therapy with human leukocyte interferon-alpha significantly improved (p <.01) phlebotomy requirements, the degree of splenomegaly, pruritus scores, iron stores and mean red cell volume values, and platelet and leukocyte counts. Interferon treatment did not produce remarkable side effects and no patient withdrew from the study because of intolerance. We conclude that subcutaneous human leukocyte interferon-alpha is an effective and well-tolerated therapy in the management of polycythemia vera-associated myeloproliferation and pruritus in patients less than 60 years old.

Adult↗
PubMed1998

Incidence of compensatory enlargement and paradoxical shrinkage of coronary arteries in presence of atherosclerotic lesions: an intracoronary ultrasound study based on multiple cross-section analysis per artery.

BACKGROUND: The aim of the study was to evaluate with intravascular ultrasound (IVUS) the incidence of compensatory enlargement and paradoxical shrinkage in 50 de novo coronary lesions, using two different approaches: 1) a single cross-section analysis and 2) a multiple cross-section analysis per artery. A 3-D IVUS system based on contour detection of lumen and plaque was applied (image acquisition speed: 0.5 mm/s, digitization rate: 5 images/s). In each cross section, we determined: 1) the lumen area (LA), 2) the external elastic membrane area (EEMA), 3) the plaque+media complex (p+m), 4) the relative EEMA = cross section EEMA/reference EEMA, 5) the relative p+m area = cross-section p+m area/reference p+m area, 6) the lumen area stenosis: 1-(cross-section LA/reference LA). In the single cross-section analysis, compensatory vessel enlargement was defined as narrowest EEMA > reference EEMA, and paradoxical vessel constriction as narrowest EEMA < reference EEMA. In the multiple cross-section analysis, compensatory vessel enlargement was defined as the presence of a significant positive correlation between relative EEMA and relative p+m area and paradoxical vessel constriction as a significant negative correlation between relative EEMA and lumen area stenosis. RESULTS: In the single cross-section analysis, compensatory vessel enlargement and paradoxical constriction occurred in 58 and 42% of cases respectively. The multiple cross-section per artery analysis showed compensatory vessel enlargement in 80% of cases and paradoxical constriction in 36% of cases and revealed the combination of compensatory enlargement with paradoxical constriction in 22% of the analyzed segments. CONCLUSIONS: Compensatory enlargement of coronary arteries was underestimated by the single cross-section analysis and was observed in 80% of cases when a multiple cross-section per artery analysis was applied. Paradoxical shrinkage was less common and often occurred in combination with compensatory enlargement within the same analyzed segment.

Adult↗
PubMed1997

Serum interleukin-10 in plasma-cell dyscrasias.

Serum levels of interleukin-10 (IL-10) were measured by enzyme-linked immunosorbent assay in 115 patients with multiple myeloma (MM) in various phases of the disease (68 at diagnosis, 22 in plateau phase, 22 in relapse), in 71 individuals with monoclonal gammopathy of undetermined significance (MGUS), and in 53 normal volunteers. Detectable levels of serum IL-10 were found in 24 myelomas (20.9%), in 7 cases of MGUS (9.9%), and in 4 normal subjects (7.5%) (P = NS, chi2 test). In patients with MM, cytokine was detected with a comparable frequency in all pathologic stages and phases of the disease: 4/19 in stage I, 6/26 in stage II, 5/23 in stage III, 4/22 in plateau phase, and 5/25 in progressing or relapsed disease. IL-10 concentrations did not differ significantly between controls and patients with plasma-cell dyscrasia, between patients with MGUS and those with MM, between early vs. advanced MM, or between patients in different phases of the disease. In 36 patients with MM in whom IL-10 was measured serially, no significant changes were observed over the course of the disease. Also, when comparing the outcomes of individuals with detectable or undetectable IL-10 in single stages or in the whole myeloma group, no differences were revealed. Our results do not support an apparent involvement of IL-10 in the pathogenesis of MM in vivo. However, further studies are required to define the exact role of this cytokine within the complex cytokine network of this neoplastic disorder.

Adult↗