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S Papageorgiou

Publications and source records attributed to S Papageorgiou.

At least 19 recordsLinked to original sources
PubMed2005

A novel p27 gene mutation in a case of unclassified myeloproliferative disorder.

P27 encodes a member of Cip/Kip family of cyclin dependent kinase inhibitors, the inactivation of which has been implicated in the pathogenesis of various hematological neoplasias. We report on a novel point mutation of this gene identified in a case of unclassified myeloproliferative syndrome consisting of a T --> C transversion at 821bp of p27 exon 1, resulting in a Ile --> Thr substitution at codon 119. The analysis of larger number of cases as well as the effect of this mutation on protein's function will help to clarify its significance in the pathogenesis of myeloproliferative syndromes.

Cell Cycle Proteins↗
PubMed2005

Non-Hodgkin's lymphomas in Greece according to the WHO classification of lymphoid neoplasms. A retrospective analysis of 810 cases.

The purpose of this retrospective study, the largest unselected series in our country, was to illustrate the clinicopathological features of non-Hodgkin's lymphoma (NHL) classified according to the World Health Organization (WHO) classification of lymphoid neoplasms. A retrospective analysis was conducted and clinical features of histological subtypes were established in 810 patients (age > or = 15 years) with NHL who were treated at 8 major centers representative of Greece. There were 435 males and 375 females 95% of them aged >30 years. B symptoms were present in 34% of the patients, while 45.3% had stages I-II and 54.6% had stages III-IV. LDH was increased in 37% of the patients. B cell lymphomas formed 88% of the cases whereas T cell lymphomas formed 12% of the total. Indolent lymphomas accounted for 31.1%, aggressive ones for 66.7% and very aggressive ones for 2.4% of all NHLs. Among indolent lymphomas extranodal ones (MALT B cell lymphoma) were the most common subset while follicular lymphoma grade I and II and small lymphocytic ones presented with equal frequency. Among the aggressive lymphomas diffuse large cell lymphoma (DLCL) was the most common subtype; this entity along with large-cell immunoblastic lymphomas accounted for 45.2% of all B cell lymphomas. Among the T cell lymphomas, peripheral T cell lymphomas and anaplastic large cell lymphomas of the T/null-cell type were the most common subtypes. The most common extranodal presentation was the gastrointestinal tract (GI). Next in frequency were primary extranodal NHL of the head and neck region. MALT B cell lymphomas were found in almost half of the patients with GI tract NHL, whereas in all other extranodal places DLCL was the predominant histological subtype. The median survival for indolent and aggressive NHL was 123.5 and 55.5 months, respectively. This is the first report of a large series of malignant lymphomas in Greece using the WHO classification. It appears that there are no significant differences between NHL in Greece and other large series as far as clinical and extranodal presentation is concerned. The frequency of follicular lymphoma in the current study is comparable to that reported from Asian countries and mainland Europe, but lower than that of US and Northern European series. There were no important differences in the incidence of the remaining histological subtypes between Greece and other European countries.

Adolescent↗
PubMed2003

Monoclonal gammopathies in B-cell non-Hodgkin's lymphomas.

The association of monoclonal gammopathy (MG) with B-cell non-Hodgkin's lymphomas (NHL) is a well known phenomenon. The aim of the present work was to study the incidence, type of monoclonal component and prognostic significance of MG in a population of 255 cases with B-cell NHL. Among 255 evaluable patients with B-cell NHL, 145 were males and 110 females with a median age of 58 years (range 18-85). There were 166 patients with the various subtypes of aggressive (intermediate/high grade) NHL and 89 with the various subtypes of low risk. MG was detected in 44 patients (17.2%) with a median age of 61 years (range 23-79). There were 22 cases (8.6%) with IgG type (IgG/(k) 15, IgG/(lambda) 7), 4 cases (1.6%) with (IgA/(k) 3, IgA/(lambda) 1) and 18 cases (7.0%) with IgM (IgM/(k) 12 IgM/(lambda) 6). MG was found in 15.6% of the patients with aggressive NHL, while in low risk NHL the incidence was 20.2% (N.S.). The type of MG according to histological classification was as follows: Aggressive NHL: IgG 17 cases, IgA 2 cases, IgM 7 cases: low risk NHL: IgG 5 cases, IgA 2 cases, IgM 11 cases. The distribution of MG according to stage of the disease was as follows: stage I (4.5%), stage II (18%), stage III (6.8%) and stage IV (70.4%). The median survival of patients with aggressive NHL with MG was 17 months compared to 40 months of those without (P=0.22). Similarly the median survival of patients with low risk NHL and MG was 51.5 months compared to 38.5 months of those without (P=0.90). In conclusion MG was detected in 17.2% of cases with B-cell NHL. IgG-MG was more frequent in cases with aggressive NHL, while IgM in cases with low risk NHL. MG was mostly associated with advanced stage and had not any prognostic significance on survival.

Adolescent↗
PubMed2003

Treatment of intermediate and advanced stage Hodgkin's disease with modified baseline BEACOPP regimen: a Hellenic Co-operative Oncology Group Study.

The purpose of this prospective phase II trial was to investigate the safety and efficacy of a modified baseline BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen in the treatment of intermediate and advanced stage Hodgkin's disease (HD). From October 1997 to November 2001, 51 consecutive, previously untreated patients with stage IIA (bulky), IIB, III, and IV disease were treated with a modified baseline BEACOPP regimen with the etoposide administered i.v. on day 1 and orally at a dose of 100 mg/m2, on days 2 and 3. Each patient was scheduled to receive eight courses of BEACOPP with consolidation radiotherapy to bulky (> or =5 cm) or residual disease. There were 25 males and 26 females with a median age of 32 yr (16-65 yr); 80.3% of the patients had nodular sclerosis HD, 41% had bulky disease (> or =5 cm), 10 were in stage IIA (bulky > or =10 cm), 15 in stage IIB, 19 in stage III, and seven in stage IV. Thirty-seven patients (72.5%) achieved a complete response and 17.6% partial response. No significant difference in overall response rate was observed between patients with: (i) 0-2 vs. > or =3 negative prognostic factors, (ii) in stage II vs. stages III/IV, LDH level, and bulky disease. With a median follow up period of 39.5 months, actuarial 3-yr survival rate is 82% and time to progression rate 72.5%. Treatment with this combination was well tolerated. Grades 3 and 4 leukopenia and neutropenia occured in 26% and 28% of the patients, respectively, whereas in 16.3% of the patients infection was observed. Support with granulocyte colony-stimulating factor was given to 59% of the patients. No case of secondary MDS/leukemia has been observed. The results of the present study demonstrate that the modified baseline BEACOPP regimen with radiotherapy used in our patients was well tolerated and effective therapy for intermediate and advanced stage HD. Further follow up time is required to evaluate long-term toxicity.

Adolescent↗
PubMed2001

Characterisation of hoxa gene expression in the chick limb bud in response to FGF.

We tested a diffusion gradient model for setting up overlapping domains of Hoxa gene expression in the chick limb bud. The model is based on morphogen production at the limb bud tip where the apical ridge is located and assumes that cells respond to a series of concentration thresholds. Consistent with the model, Hoxa13 gene expression rapidly switches off when the ridge is removed from stage 21/22 buds, while Hoxa11 and Hoxa10 expression is stable; Hoxa13 expression can be initiated and maintained in absence of the ridge by FGF soaked beads; the Hoxa13 domain first expands quickly and then slows up and the size is related to the dose of FGF4. Contrary to the model, addition of FGF4 to early limb buds does not activate Hoxa13 prematurely nor extend the Hoxa13 expression domain proximally. Therefore FGF4 signalling is necessary but not sufficient for Hoxa gene expression in the limb bud.

Animals↗
PubMed2001

A physical force may expose Hox genes to express in a morphogenetic density gradient.

In both invertebrates and vertebrates, a set of homeobox genes is involved in the primary pattern formation along the anterior-posterior axis of the developing organism. In particular, the genes of the Hox/HOM complex are located in a physical order in the 3' to 5' direction of the gene clusters. Furthermore, the vertebrate genes of the Hoxa and Hoxd clusters are expressed following the empirical rules of temporal and spatial collinearities: the genes are expressed one after the other according to their positional order and their domains of expression start anteriorly and move gradually towards more posterior locations along the developmental axis. The mechanism that controls this remarkable expression behaviour remains elusive. A proposed morphogen gradient model could justify the serial gene expression in space and time during vertebrate limb development. It is therefore likely that a morphogen concentration ordering might cause the sequential gene expression. I put forward this hypothesis and explore some possibilities that concentration-dependent physical forces might push the Hoxa,d clusters to an environment where the transcriptional activity of the genes is possible. The suggested mechanisms offer satisfactory concentration resolution for differential gene expression. Some experiments are proposed to test the presence of such forces. The verification of this hypothesis would provide a solution to the interpretation problem of the positional information theory in development. Furthermore, it would broaden our knowledge of how gene transcription can be triggered.

Animals↗
PubMed1999

Modes of morphogen cooperation for limb formation in vertebrates and insects.

Diffusing morphogens in cooperation can control gene expression in developing limbs. Additive cooperation corresponds to the Boolean operator OR and implies the equivalent action of the (suitably scaled) concentrations of two morphogens, either by their alternative binding to the same receptor or by another way of convergence of their effects during the signal transduction procedure. This cooperation can explain the spatial and temporal collinearities of the expression of hoxd genes in the vertebrate limb bud. A multiplicative cooperation of morphogens (corresponding to the Boolean operator AND), produced at the DPP and WG domains in the Drosophila leg imaginal disc, may account for the expression domains observed for Dll and dac. A molecular interpretation of the multiplicative morphogen cooperation is proposed. Some experiments are suggested for further testing of the model.

Animals↗
PubMed1998

Cooperating morphogens control hoxd gene expression in the developing vertebrate limb.

A mechanism was recently proposed which controls the expression of Hoxa genes in the developing vertebrate limb. This is a three-dimensional diffusion model of a morphogen Ma secreted at the apical ectodermal ridge. The morphogen Ma is at the same time degraded by first order chemical kinetics. The emerging diffusion gradient, supplemented with a natural sequence of thresholds, can explain the spatial and temporal collinearities of the Hoxa gene expression domains. In the present model it is assumed that a second diffusing morphogen Mz is produced at the zone of polarizing activity. A concentration superposition of morphogens Ma and Mz can then explain the observed pattern of expression of Hoxd-10, 11, 12, and 13 during normal limb development (spatial and temporal collinearity). The associated thresholds for gene expression increase sequentially from Hoxd-10 to Hoxd-13 (threshold collinearity). The observed deformations or deletions of these expression domains in manipulated limbs are also explained by the model. Additional model predictions are proposed to test the validity of the model. In patterning two mechanisms are mainly considered as responsible for signalling: (i) a gradient of a long-range morphogen created by passive diffusion; and (ii) a short-range inducer initiating a cascade of consecutive signals. A time-test is proposed which distinguishes the modes of specific gene expressions for these distinct signalling mechanisms.

Animals↗
PubMed1998

Relevance of divalent cations to ATP-driven proton pumping in beef heart mitochondrial F0F1-ATPase.

The ATP hydrolysis rate and the ATP hydrolysis-linked proton translocation by the F0F1-ATPase of beef heart submitochondrial particles were examined in the presence of several divalent metal cations. All Me-ATP complexes tested sustained ATP hydrolysis, although to a different extent. However, only Mg- and Mn-ATP-dependent hydrolysis could sustain a high level of proton pumping activity, as determined by acridine fluorescence quenching. Moreover, the Km of the Me-ATP hydrolysis-induced proton pumping activity was very similar to the Km value of Me-ATP hydrolysis. Both oligomycin and DCCD caused the full recovery of the fluorescence, providing clear evidence for the association of Mg-ATP hydrolysis with proton translocation through the F0F1-ATPase complex. In contrast, with other Me-ATP complexes, including Ca-ATP as substrate, the proton pumping activity was undetectable, implicating an uncoupling nature for these substrates. Attempts to demonstrate the involvement of the epsilon subunit of the enzyme in the coupling mechanism failed, suggesting that the participation of at least the N-terminal segment of the subunit in the coupling mechanism of the mitochondrial enzyme is unlikely.

Adenosine Triphosphate↗
PubMed1996

Gradient model describes the spatial-temporal expression pattern of Hoxa genes in the developing vertebrate limb.

Pattern formation of the developing vertebrate limb is mainly controlled by the zone of polarizing activity (ZPA) and the apical ectodermal ridge (AER) which may act as sources of diffusing morphogens. These sources are tightly interconnected and maintained by positive feedback and, together with the established role of Wnt7 a on the dorsal side of the bud, they constitute a cartesian reference frame for the processes of patterning and growth of the limb bud. As an input to our model we have used the local extent and temporal activity of the AER source as it is reflected by Fgf-4 expression in the ridge. We have assumed that this source produces a morphogen which diffuses in the three-dimensional limb field and degradates by first-order kinetics. When in a cell the morphogen concentration exceeds a particular threshold value, a gene is switched on. To every threshold corresponds a specific gene. In the following we introduce an order of increasing concentration thresholds corresponding to the sequence of Hoxa-10, 11, and 13 genes (threshold collinearity). With this simple rule of correspondence we can reproduce both spatial and temporal collinearities of Hoxa gene expression. This outcome may be the first direct observable effect of a putative morphogen in the developing limb. The expression patterns are essentially transient, and they are followed by sequential refinements which lead to the final limb structures. Furthermore, the continuous flow of the morphogen through the progress zone guarantees the coherent course of patterning and limb growth. Several experiments are proposed for additional tests of the validity of the model and the eventual reversibility of Hoxa gene expression.

Aging↗
PubMed1996

Quantitation of benzodiazepine receptors in human brain using the partial saturation method.

UNLABELLED: The in vivo quantification of the benzodiazepine receptor concentration in humans using PET and flumazenil (FMZ) is usually based on Scatchard analysis when the goal is to avoid blood sampling. The experimental protocols, however, include several (at least two) experiments with various specific activities in the same subject to obtain a range of bound ligand concentrations. METHODS: We propose the partial saturation method, which is based on a natural decrease in bound ligand concentration after an FMZ injection with an average dose between a tracer dose and a saturation dose. An adequate range of bound ligand concentrations can thus be obtained from a single experiment. The free ligand concentration is estimated from the PET measurement in the pons after correction for the effect of the small receptor site concentration in this reference region. RESULTS: The receptor concentration and affinity estimates obtained with this approach in six regions of interest agree with previously published values obtained by using more complex approaches. Receptor concentration appears to be insensitive to the uncertainties with regard to the receptor site concentration in the pons. CONCLUSION: The partial saturation protocol can be used to estimate both the benzodiazepine receptor concentration and the FMZ affinity in routine examinations in adults (or even in children) using a single 40-min experiment without blood sampling.

Adult↗
PubMed1995

Is interictal temporal hypometabolism related to mesial temporal sclerosis? A positron emission tomography/magnetic resonance imaging confrontation.

The mechanism of interictal glucose hypometabolism remains unclear, but this abnormality occurs more frequently in temporal lobe epilepsy (TLE) than in other types of partial epilepsy. Therefore temporal hypometabolism has been suggested to reflect mesial temporal sclerosis (MTS). To investigate this, we selected 22 patients with refractory partial epilepsy of mesial temporal lobe origin (MTLE) who had hippocampal atrophy based on magnetic resonance imaging (MRI) volumetric analysis. We then analyzed the metabolic correlates of unilateral hippocampal atrophy. Thirteen temporal regions of interest (ROI) were defined on MRI scans for each individual and then applied to high-resolution FDG-positron emission tomography (PET) images obtained parallel to the long axis of the hippocampus. The most hypometabolic regions were the temporal pole and the hippocampal region. When we analyzed ensembles of temporal regions grouped into related networks, the temporolimbic network, which included the hippocampal region and the temporal pole, was abnormal in 95% of the patients at a 3-SD threshold. PET hypometabolism was highly correlated with the degree of hippocampal atrophy in this network, but not in other parts of the temporal lobe, which were less frequently hypometabolic. These data indicate that hypometabolism is a consequence of MTS in the temporolimbic region but not necessarily in the other parts of the temporal lobe. Our results also suggest that the combination of PET and MRI may facilitate the noninvasive diagnosis of MTLE.

Adult↗
PubMed1992

Diffusion or autocatalysis of retinoic acid cannot explain pattern formation in the chick wing bud.

We have collected several experimental data of pattern duplications due to the ZPA transplantation or application of retinoic acid on the developing chick limb bud. We have compared these data with the predictions of models based on diffusion or autocatalysis of retinoids. It turns out that these models cannot comprehensively explain the data. More specifically, retinoic acid cannot be either diffusing from a ZPA source or participate in an autocatalytic gradient formation.

Animals↗
PubMed1989

Diverse supernumerary structures develop after inverting the anteroposterior limb axis of the anuran.

Contralateral limb bud graftings were performed on tadpoles of the anuran Bufo bufo. The anteroposterior axis was inverted while the larvae were at stage IV or V (e.g., between 22-30 days after fertilization). Eighty-four tadpoles were operated on, 10 of which were used as controls. At anterior or posterior location 104 supernumerary structures developed in toto. They were collected and whole-mount examined after being stained with Alcian blue. They were further prepared for serial sectioning, mounting, and staining with hematoxylin and eosin. The majority of these supernumerary structures were found to be normal limbs of the stump handedness in agreement with all models and experiments on the urodeles axolotl and newt. However, some of the structures were clearly abnormal: double symmetric or of mixed handedness. This result is consistent with a prediction of a hierarchical polar coordinate model. The fact that no such structures have been found in the experiments on the urodeles may be due to the expected low probability for their appearance and the fact that only few such limbs have been sectioned and analyzed as yet.

Alcian Blue↗