AD‐HIES or Job's syndrome is a primary immunodeficiency, caused by dominant negative mutations in signal transducer and activator of transcription (STAT) 3. The syndrome is characterized by infectious, immunologic, and non‐immunologic... more
AD‐HIES or Job's syndrome is a primary immunodeficiency, caused by dominant negative mutations in signal transducer and activator of transcription (STAT) 3. The syndrome is characterized by infectious, immunologic, and non‐immunologic manifestations and is associated with significant morbidity, mortality, and development of lymphomas. What has not yet been elucidated is the role of HSCT in the disease treatment spectrum. We review published cases of patients with AD‐HIES that underwent HSCT and attempt to clarify at what stage HSCT should be considered and what are the complications.
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Research Interests: Cardiology, Nonparametric Statistics, Medicine, Echocardiography, Humans, and 15 moreInternal Medicine, Female, Male, Confidence intervals, Bone marrow, Glycoproteins, European, Middle Aged, Bone Marrow Transplantation, Myocardial Infarction, Adult, Myocardium, Ejection Fraction, inotrope, and Cardiovascular medicine and haematology
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Research Interests: Thalassemia, Adolescent, Medicine, Transplantation, Humans, and 14 moreChild, Internal Medicine, Testosterone, Female, Male, Bone Marrow Transplantation, Pediatric Endocrinology and Metabolism, Pubic Hair, Beta Thalassemia, Luteinizing Hormone, Follicle stimulating hormone, Child preschool, hypogonadism, and Paediatrics and reproductive medicine
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Research Interests: Biology, Cell separation, Cell Differentiation, Cellular, Humans, and 15 moreChild, Bone marrow, Haematopoiesis, CD, Clinical Sciences, Adult, Immunophenotyping, Cellular and Molecular Medicine, Cell Proliferation, Lymphocytes, Comparative Genomic Hybridization, Bone Marrow Cells, Biochemistry and cell biology, Endoglin, and Cell culture techniques
Research Interests: Endocrinology, Cognitive Science, Biology, Inflammation, Medicine, and 15 moreHematopoiesis, Clinical Chemistry, Erythropoietin, Humans, Internal Medicine, Bone marrow, Haematopoiesis, Athletes, Clinical Sciences, Erythropoiesis, Biological markers, Physical Exercise, Acute Phase Proteins, Biological activity, and physical exertion
Long-term disease control is achieved in 80–90% of patients with acute lymphoblastic leukemia of B origin (B-ALL). About half of adult and 10% of pediatric patients develop refractory or relapsed disease, whereas survival after relapse... more
Long-term disease control is achieved in 80–90% of patients with acute lymphoblastic leukemia of B origin (B-ALL). About half of adult and 10% of pediatric patients develop refractory or relapsed disease, whereas survival after relapse accounts about 10% in adults and 30–50% in children. Allogeneic bone marrow transplantation offers remarkable benefit in cases with unfavorable outcome. Nevertheless, novel immunotherapeutic options have been approved for patients with adverse prognosis. Immunotherapeutic agents, nowadays, are preferred over standard chemotherapy for patients with relapsed or refractory B-ALL The mode of action, efficacy and safety data of immunotherapeutic agents released, indications and sequence of those therapies over the course of treatment, are herein reviewed.
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Several cord blood banks store cord blood units from healthy siblings of patients, who are candidates for stem cell transplantation. We analyzed the quality characteristics of 50 cord blood units collected from families with... more
Several cord blood banks store cord blood units from healthy siblings of patients, who are candidates for stem cell transplantation. We analyzed the quality characteristics of 50 cord blood units collected from families with beta-thalassemia major and the outcome of subsequent stem cell transplantations during a 15-year period. All cord blood units were found suitable for banking based on a minimum net volume of 40 ml. The mean volume of the units was 98.9 ml; the mean total nucleated cell count (NC) was 7.8 x 10(8) and the mean CD34+ cell count was 2.8 x 10(6). Eight out of twelve HLA matched collections were released for transplantation. All but one recipient belonged to Pesaro II-III risk classes. Three patients received a cord blood graft with >5 x 10(7) NC/kg . One of them with Pesaro class I disease engrafted, whereas the other two who failed to engraft, were re-transplanted with bone marrow from the same donor later. Cord blood grafts containing NCs <4 x 10(7)/kg combined with reduced volume bone marrow from the same donor were used in all 5 remaining cases and stable engraftment was achieved. All patients survived, 7/8 thalassemia-free. Cord blood banking from healthy siblings of children with beta-thalassemia major can result in a successful transplantation in cases in which there is HLA compatibility. However, in high-risk patients, the use of combined cord blood and bone marrow grafts seems necessary in order to ensure stable engraftment, especially when cord blood unit cell counts are low.
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Synthetic modified mRNA molecules encoding pluripotency transcription factors have been used successfully in reprogramming human fibroblasts to induced pluripotent stem cells (iPSCs). We have applied this method on bone marrow-derived... more
Synthetic modified mRNA molecules encoding pluripotency transcription factors have been used successfully in reprogramming human fibroblasts to induced pluripotent stem cells (iPSCs). We have applied this method on bone marrow-derived mesenchymal stromal cells (BM-MSCs) obtained from a patient with β-thalassemia (β-thal) with the aim to generate trangene-free β-thal-iPSCs. Transfection of 10(4) BM-MSCs by lipofection with mRNA encoding the reprogramming factors Oct4, Klf4, Sox2, cMyc, and Lin28 resulted in formation of five iPSC colonies, from which three were picked up and expanded in β-thal-iPSC lines. After 10 serial passages in vitro, β-thal-iPSCs maintain genetic stability as shown by array comparative genomic hybridization (aCGH) and are capable of forming embryoid bodies in vitro and teratomas in vivo. Their gene expression profile compared to human embryonic stem cells (ESCs) and BM-MSCs seems to be similar to that of ESCs, whereas it differs from the profile of the parental BM-MSCs. Differentiation cultures toward a hematopoietic lineage showed the generation of CD34(+) progenitors up to 10%, but with a decreased hematopoietic colony-forming capability. In conclusion, we report herein the generation of transgene-free β-thal-iPSCs that could be widely used for disease modeling and gene therapy applications. Moreover, it was demonstrated that the mRNA-based reprogramming method, used mainly in fibroblasts, is also suitable for reprogramming of human BM-MSCs.
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Beta-thalassaemia is caused by gene mutations that reduce or abrogate the production of b-globin, causing severe anaemia, chronic haemolysis, and iron overload. Supportive care with intensive transfusions and effective iron chelation is... more
Beta-thalassaemia is caused by gene mutations that reduce or abrogate the production of b-globin, causing severe anaemia, chronic haemolysis, and iron overload. Supportive care with intensive transfusions and effective iron chelation is mandatory. Until now, despite the novel therapeutic promise of targeted gene therapy, allogeneic haematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA)matched sibling donor (MSD) at a young age remains the ‘gold standard’. Yet, MSDs are available only for ~20% of patients. HSCT from a matched unrelated donor (MUD) is a safe alternative in terms of overall survival (OS) and transfusion-free survival (TFS), but is associated with frequent transplant-related complications and increased morbidity. Although post-HSCT immune-mediated cytopenias (ICs) represent a complication with a possible serious impact on quality of life, limited data are reported on the incidence and predictors of ICs in thalassaemic patients. This was the...
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Carbapenem resistance, most notably in Klebsiella pneumonia (KPC), results in infections associated with significant morbidity and mortality. Here we report 2 cases of adolescent patients with KPC infection after high-risk bone marrow... more
Carbapenem resistance, most notably in Klebsiella pneumonia (KPC), results in infections associated with significant morbidity and mortality. Here we report 2 cases of adolescent patients with KPC infection after high-risk bone marrow transplantation, who eventually succumbed from other causes and review the epidemiology and treatment options for KPC infections in this vulnerable population.
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Lower respiratory tract infections (LRTI), due to community acquired respiratory viruses such as respiratory syncytial virus (RSV) and parainfluenza (PIV), in patients after allogeneic hematopoietic stem cell transplantation (alloSCT) are... more
Lower respiratory tract infections (LRTI), due to community acquired respiratory viruses such as respiratory syncytial virus (RSV) and parainfluenza (PIV), in patients after allogeneic hematopoietic stem cell transplantation (alloSCT) are associated with significant morbidity and mortality. The severity of immunodeficiency is directly associated with a high probability for rapid progression to LTRI, respiratory failure needing mechanical ventilation and a fatal outcome [1]. Shah et al. [2] developed an immunodeficiency scoring index (ISI-RSV) with the aim to predict the risk of progression to LRTI and RSV-associated mortality. Based on the presence or absence of several parameters, patients are stratified into low, moderate, and high-risk group with a probability of progression to LTRI of 7%, 15%, 48%, and RSV-associated mortality of 0%, 3%, and 29%, respectively. At present, there are no drugs licensed for the treatment of RSV or PIV infection. Ribavirin is recommended by many experts for the treatment of severe non-influenza respiratory virus infections in immunosuppressed patients. However, it is important to note that this recommendation is based on retrospective data from case reports and small series. In this study, we report the Greek experience with the use of oral ribavirin with or without the addition of immune gamma-globulin (IVIgG) in allo-SCT recipients with LTRI, due to RSV and PIV3. The study was performed in three BMT centers in Athens, Greece (two adult and 1 pediatric center). Between December/2010 and December/2019, 52 episodes of LRTI due to RSV or PIV3 were recorded in 47 patients after allo-SCT. In more detail, only one infectious episode occurred in 44 patients, one patient had three different RSV infectious episodes developed during a period of 18 months, while a second RSV episode occurred in two patients with a time-interval of 3 and 9 months after the initial episode. LRTI was defined according to the following criteria: (1) presence of lower respiratory tract (LRT) symptoms and/or abnormal radiographic findings, and (2) identification of virus in samples from respiratory tract [3]. The decision for bronchoscopy and bronchoalveolar lavage (BAL) was at the discretion of treating physician. In eight patient/episodes with significant respiratory distress, abnormal radiological findings, positive viral testing in nasopharyngeal lavage (NPL), absence of any other identifiable infectious agent, and clinical improvement after 2–3 days of ribavirin treatment, bronchoscopy was not performed. In seven cases admitted with severe respiratory failure, bronchoscopy and BAL was performed after * Panagiotis Tsirigotis panagtsirigotis@gmail.com
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Endoglin (CD105) is an accessory protein of the transforming growth factor-β receptor system expressed on vascular endothelial cells. Mutations on the endoglin gene are associated with hereditary hemorrhagic telangiectasias... more
Endoglin (CD105) is an accessory protein of the transforming growth factor-β receptor system expressed on vascular endothelial cells. Mutations on the endoglin gene are associated with hereditary hemorrhagic telangiectasias (Osler-Weber-Rendu syndrome) and, thus, endoglin has been extensively studied in the context of this disease. Endoglin is highly expressed on endothelial cells in healing wounds, developing embryos, inflammatory tissues and solid tumors. It is a marker of activated endothelium, while its vascular expression is limited to proliferating cells. Previous studies have shown that the endothelial function is impaired in patients with Thalassemia Intermedia (TI). Oxidative damage resulting from hemolysis and iron load, leads to increased expression of the intercellular and vascular adhesion molecules-1 (ICAM-1 and VCAM-1) and impaired nitric oxide (NO) bioavailability. As endoglin plays a critical role in angiogenesis and dysregulation of its expression and/or activity h...
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The “Spartathlon” ultradistance foot race (246 Km continuous, prolonged, brisk exercise for up to 36 hours) provides a unique model of prolonged duration exercise that reveals dramatic systemic inflammatory changes. Endothelial progenitor... more
The “Spartathlon” ultradistance foot race (246 Km continuous, prolonged, brisk exercise for up to 36 hours) provides a unique model of prolonged duration exercise that reveals dramatic systemic inflammatory changes. Endothelial progenitor cells (EPCs) have been shown to participate in vascular repair and angiogenesis, while circulating bone marrow originated fibrocytes represent multipotent cells mediating tissue repair and remodeling after injury. In this study we investigated the effect of this type of exercise on the number of circulating EPCs and fibrocytes along with molecules of endothelium dysfunction and chemotactic proteins in 10 “Spartathlon” athletes before, at the end and at 48 h post race. The EPCs were obtained by culturing peripheral blood mononuclear cells (PBMC) under endothelial cell conditions (EndoCult) and were measured as colony-forming units (CFUs). Circulating fibrocytes were cultured from PBMCs in IMDM medium supplemented with IL-3 and M-CSF and identified a...
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Toxoplasmosis is a disease of the immunocompetent population. However, cases of toxoplasma infection associated with immunosuppression have been reported, especially the first months after transplantation. Limited data are available about... more
Toxoplasmosis is a disease of the immunocompetent population. However, cases of toxoplasma infection associated with immunosuppression have been reported, especially the first months after transplantation. Limited data are available about toxoplasma infection, occurring even many months post‐transplant in pediatric patients with nonmalignant and malignant diseases. We report the cases of three patients with early and late disseminated toxoplasmosis and review the literature.
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Introduction Lower respiratory tract infections (LRTI) due to parainfluenza (PIF) or respiratory syncytial virus (RSV) represent a major challenge for immunocompromised patients especially those after allogeneic stem cell transplantation... more
Introduction Lower respiratory tract infections (LRTI) due to parainfluenza (PIF) or respiratory syncytial virus (RSV) represent a major challenge for immunocompromised patients especially those after allogeneic stem cell transplantation (allo-SCT). Evidence-based guidelines for the management of respiratory virus infections in allo-SCT recipients are limited due to the paucity of effective antivirals and the lack of prospective randomized trials. In this study, we report our experience with the use of oral ribavirin with or without the addition of IVIgG in allo-SCT recipients with LTRI due to RSV and PIF. Patients and methods This is a retrospective study performed in 3 BMT centers in Athens, Greece (2 adult and 1 pediatric center). Review of medical records was performed with the aim to identify patients with RTIs who received treatment with oral ribavirin. LRTI was defined according to the European Conference on Infections in Leukaemia (ECIL-4) (Ref 1). Presence of RSV or PIF in ...
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Acute inflammatory bowel disease (AIBD) is a wide clinical entity including severe gastrointestinal pathologies with common histopathological basis. Epidemiologically increasing diseases, such as necrotizing enterocolitis (NEC),... more
Acute inflammatory bowel disease (AIBD) is a wide clinical entity including severe gastrointestinal pathologies with common histopathological basis. Epidemiologically increasing diseases, such as necrotizing enterocolitis (NEC), gastrointestinal graft versus host disease (GVHD), and the primary acute phase of chronic inflammatory bowel disease (CIBD), exhibit a high necessity for new therapeutic strategies. Mesenchymal stem cell (MSC) cellular therapy represents a promising option for the treatment of these diseases. In our study, we comparatively assess the efficacy of human MSCs derived from bone marrow (BM), umbilical cord blood (UCB), human embryonic stem cells (ESCs), or human-induced pluripotent stem cells (iPSCs) in a mouse model of chemically induced acute enterocolitis. The laboratory animals were provided ad libitum potable dextrane sulfate sodium solution (DSS) in order to reproduce an AIBD model and then individually exposed intraperitoneally to MSCs derived from BM (BM-MSCs), UCB (UCB-MSCs), ESCs (ESC-MSCs), or iPSCs (iPSC-MSCs). The parameters used to evaluate the cellular treatment efficacy were the animal survival prolongation and the histopathological-macroscopic picture of bowel sections. Although all categories of mesenchymal stem cells led to statistically significant survival prolongation compared to the control group, significant clinical and histopathological improvement was observed only in mice receiving BM-MSCs and UCB-MSCs. Our results demonstrated that the in vivo anti-inflammatory effect of ESC-MSCs and iPSC-MSCs was inferior to that of UCB-MSCs and BM-MSCs. Further investigation will clarify the potential of ESCs and iPSC-derived MSCs in AIBD treatment.
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Abstract Respiratory infections in oncology are both common and potentially severe. However, there is still a gap in the literature, regarding the epidemiology of viral respiratory infections in children with cancer. We prospectively... more
Abstract Respiratory infections in oncology are both common and potentially severe. However, there is still a gap in the literature, regarding the epidemiology of viral respiratory infections in children with cancer. We prospectively enrolled 224 patients, from September 2012 to August 2015. The cohort included children with hematologic or solid malignancies receiving chemotherapy, or undergoing hemopoietic stem cell transplantation, outpatients/inpatients exhibiting signs/symptoms of febrile/afebrile upper/lower respiratory infection. Viral infection was diagnosed by detection of ≥1 viruses from a sample at time of enrollment, using the CLART® PneumoVir kit (GENOMICA, Spain). Α detailed questionnaire including demographics and medical history was also completed. Samples were processed in batches, results were communicated as soon as they became available. Children recruited in whom no virus was detected composed the no virus detected group. Viral prevalence was 38.4% in children presenting with respiratory illness. A single virus was found in 30.4%, with RSV being the most frequent. Viral coinfections were detected in 8%. Children with viral infection were more likely to be febrile upon enrollment and to present with lower respiratory signs/symptoms. They had longer duration of illness and they were more likely to receive antibiotics/antifungals. Only 22% of children with influenza received oseltamivir. Mortality was low (2.7%), however, pediatric intensive care unit (PICU) admission and death were correlated with virus detection. In our study mortality was low and PICU admission was related to virus identification. Further research is needed to clarify whether antibiotics in virus-proven infection are of value and underline the importance of oseltamivir’s timely administration in influenza.
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Voriconazole levels were determined with high-performance liquid chromatography (HPLC) and a microbiological agar diffusion assay using aCandida parapsilosisisolate in 103 serum samples from an HPLC-tested external quality control program... more
Voriconazole levels were determined with high-performance liquid chromatography (HPLC) and a microbiological agar diffusion assay using aCandida parapsilosisisolate in 103 serum samples from an HPLC-tested external quality control program (n= 39), 21 patients receiving voriconazole monotherapy (n= 39), and 7 patients receiving combination therapy (n= 25). The results of the bioassay were correlated with the results obtained from the external quality control program samples and with the HPLC results in sera from patients on voriconazole monotherapy and on combination therapy with an echinocandin (Spearman's rank correlation coefficient [rs], > 0.93; mean ± standard error of the mean [SEM] % difference, <12% ± 3.8%).
Research Interests: Microbiology, Medical Microbiology, Quality Control, Humans, Candida, and 10 moreCandidiasis, Regression Analysis, High Pressure Liquid Chromatography, Voriconazole, Reproducibility of Results, Antifungal Agents, Combination drug therapy, Sensitivity and Specificity, Biological Assay, and Pharmacology and pharmaceutical sciences
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We report successful bone marrow transplantation in an 11-year-old male with chronic myeloid leukemia from his HLA-identical sibling selected by preimplantation HLA testing. Because collection of cord blood failed, the transplantation was... more
We report successful bone marrow transplantation in an 11-year-old male with chronic myeloid leukemia from his HLA-identical sibling selected by preimplantation HLA testing. Because collection of cord blood failed, the transplantation was performed when the donor reached the age of 19 months, and sufficient bone marrow could be harvested safely. The patient was BCR/ABL negative at the time of transplantation after complete molecular response to imatinib. Currently, 16 months post-transplantation he is well and in complete molecular remission. This report describes preimplantation HLA-genotyping to deliver a matched sibling donor for successful transplantation of a malignant disorder.
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Research Interests: Polymorphism, Biology, Cytokines, Adolescent, Medicine, and 15 moreMultivariate Analysis, Greece, Humans, Child, Cox Regression, Haplotypes, Infant, Gene Polymorphism, Retrospective Studies, Risk Factors, Overall Survival, Confidence Interval, Interferon gamma, Hematopoietic Stem Cell Transplantation, and Child preschool
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Abstract The origin (recipient/donor) of the myofibroblasts mediating fibrosis in sclerodermatous chronic graft-versus-host disease (cGvHD) was investigated. Sclerodermatous specimens obtained from a patient with extensive cGvHD after an... more
Abstract The origin (recipient/donor) of the myofibroblasts mediating fibrosis in sclerodermatous chronic graft-versus-host disease (cGvHD) was investigated. Sclerodermatous specimens obtained from a patient with extensive cGvHD after an HLA-identical sibling bone marrow transplantation were cultured in order to derive tissue myofibroblasts. All proliferating a-SMA+ fibroblastoid cells revealed recipient origin as examined by variable number tandem repeat (VNTR)-PCR. This case report shows that fibrosis in sclerodermatous lesions results from the activation and proliferation of locally-derived recipient fibroblasts rather than from donor-derived fibroblasts or circulating fibrocytes.
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Research Interests: Technology, Stem Cells, Flow Cytometry, Biology, Medicine, and 15 moreBiological Sciences, Humans, Chronic Disease, Male, Follow-up studies, Peptides, Bone marrow, Glycoproteins, Middle Aged, Bone Marrow Transplantation, Adult, Myocardium, Bone Marrow Cells, Myocardial Ischemia, and Medical and Health Sciences
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To investigate the effect of a long-distance endurance exercise &quot;Spartathlon&quot; on erythrocyte glucose-6-phosphate dehydrogenase (G(6)PD) activity. The study comprised 15 male runners, median age 36.5 years. Blood samples... more
To investigate the effect of a long-distance endurance exercise &quot;Spartathlon&quot; on erythrocyte glucose-6-phosphate dehydrogenase (G(6)PD) activity. The study comprised 15 male runners, median age 36.5 years. Blood samples were obtained in the 15 min before the race and again within 15 min after the end of the race. Erythrocyte glutathione (GSH and GSSG) and plasma malonyldialdehyde were measured with HPLC methods, and total antioxidant capacity (TAC), total hyperoxides and G(6)PD activity with commercial kits. Lipids, uric acid and total bilirubin were determined with a clinical chemistry analyser. Total hyperoxides were found statistically reduced, whereas total bilirubin was measured elevated post-race. Interestingly, GSSG levels were found increased (167.3+/-12.0 versus 219.5+/-20.3 micromol/L; p&lt;0.005) as well as GSSG/GSH ratio (16.0+/-1.3 versus 20.60+/-1.65; p&lt;0.05) post-race. In contrast, G(6)PD activity was found remarkably decreased (8.72+/-3.10 versus 3.8+/-2.5 U/g Hb; p&lt;0.0001) pre versus post the event. Red blood cell G(6)PD activity in athletes may be reduced post-race as a consequence of the modulation of NADP/NADPH levels and elevation of the erythrocyte GSSG, and especially GSSG/GSH ratio, resulting in an impairment of the hexose monophosphate shunt.
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ADEM is a rare inflammatory demyelinating disease of the CNS, which usually presents after a viral infection or a vaccination. We report a 15-yr-old boy who was diagnosed with ADEM after an HLA-identical sibling allogeneic BMT for... more
ADEM is a rare inflammatory demyelinating disease of the CNS, which usually presents after a viral infection or a vaccination. We report a 15-yr-old boy who was diagnosed with ADEM after an HLA-identical sibling allogeneic BMT for transfusion-dependent PRCA. His course was complicated with GVHD affecting the skin and lungs. Five months post-BMT, he developed neurological symptoms including sudden mental status alteration, dysarthria, facial nerve palsy, and acute paraplegia. The MRI revealed multifocal hyperintense lesions mainly in the subcortical white matter of the cerebrum, the brainstem, the basal ganglia, and the thalami. CSF examination was normal. There was no laboratory evidence of infection. The typical MRI findings and an acute monophasic clinical course were consistent with the diagnosis of ADEM. Clinical and radiological improvement was observed after treatment with high-dose steroids and IVIG. Complete neurologic recovery was achieved six months after the onset of symptoms. We present a rare case of ADEM post-BMT and review of the literature.
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Chronic myeloid leukemia (CML) represents a rare myeloproliferative disease among children where allogeneic stem cell transplantation (SCT) remains the curative gold standard. However, the impressive early cytogenetic and molecular... more
Chronic myeloid leukemia (CML) represents a rare myeloproliferative disease among children where allogeneic stem cell transplantation (SCT) remains the curative gold standard. However, the impressive early cytogenetic and molecular responses achieved by tyrosine kinase inhibitors [TKIs (imatinib, nilotinib, and dasatinib)] as first-line or even sole treatment in adults, has led to their increasing use also among children. Due to limited data regarding long-term results of TKIs and especially those of second generation in pediatric cohorts, we would like to add clinical information in this rare series of patients by reporting on four children with CML over a 10-year period, focusing on TKIs, dose escalations and clinical responses.
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We report on the development of steroid-refractory recurrent cytopenias in a child with 22q11.2 deletion syndrome. His first hematological complication was autoimmune hemolytic anemia at 3 months of age. Thereafter, he developed severe... more
We report on the development of steroid-refractory recurrent cytopenias in a child with 22q11.2 deletion syndrome. His first hematological complication was autoimmune hemolytic anemia at 3 months of age. Thereafter, he developed severe autoimmune cytopenias of all 3 hematological lineages with poor response to steroids and intravenous immunoglobulin. At the age of 2½ years, a course of anti-CD20 therapy (Rituximab) was given with transient hematological recovery. Because of persistent symptoms, bone marrow transplantation from a matched unrelated donor was performed. Although the data in the use of anti-CD20 therapy in children with 22q11.2 deletion syndrome and autoimmune cytopenias are limited, our experience suggests its potential benefit.
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The most primitive engrafting hematopoietic stem cell (HSC) resides mainly in a tumor growth factor-beta (TGF-beta)-dependent quiescent phase of the cell cycle. In this study, ex vivo expansion of UC blood (UCB) HSCs has been... more
The most primitive engrafting hematopoietic stem cell (HSC) resides mainly in a tumor growth factor-beta (TGF-beta)-dependent quiescent phase of the cell cycle. In this study, ex vivo expansion of UC blood (UCB) HSCs has been investigated, with the aim of showing whether quiescent HSCs can be recovered from expansion culture. AC133(+) stem/progenitor cells from six full term-pregnancies UCB-samples were immunomagnetically selected, followed by ex vivo expansion culture in the presence of thrombopoietin (TPO), c-kit ligand (KL), flt-3 ligand (FL) and IL-6. Quiescent HSCs were detected by a clonogenic assay that allows the detection of multipotent and committed single- lineage quiescent stem/progenitor cells, named mHPP-Q and cHPP-Q, respectively, by means of a TGF-beta blocking Ab. Expansion culture of fresh selected AC133(+) cells for 1 week caused maintenance rather than expansion of mHPP-Q cells and a 1-fold increase in cHPP-Q cells. A further week culture initiated with 7-day expanded AC133(+) cells resulted in an additional 1.5-fold expansion of cHPP-Q while no mHPP-Q cells could be detected. Amplification of cHPP-Q cells in long-term expansion cultures initiated with 14-day expanded AC133(+) cells was observed for at least a further 4 weeks. A small proportion of HPP-Q cells recovered from 7-day expansion cultures retain their multilineage potential: longer culturing of these cells results in the loss of multilineage potential while they maintain quiescent behavior and high proliferative potential.
Research Interests: Kinetics, Flow Cytometry, Macrophages, Stem Cell, Cell Division, and 14 moreAntibodies, Hematopoietic Stem Cells, Cell Differentiation, Humans, Cord Blood, Peptides, Glycoproteins, Clinical Sciences, Time Factors, Transforming Growth Factor Beta, Somatic Cell Count, Cell count, Cytotherapy, and Immunomagnetic separation
Hyperinsulinemia with or without DM2 is a frequent long-term sequela of BMT, especially following cGvHD. In this report, an extensive evaluation of a patient with cGvHD is described: glucose and insulin during OGTT, markers of... more
Hyperinsulinemia with or without DM2 is a frequent long-term sequela of BMT, especially following cGvHD. In this report, an extensive evaluation of a patient with cGvHD is described: glucose and insulin during OGTT, markers of inflammation, adiponectin and RBP4, body composition analysis, and the kinetics of GLUT3 and GLUT4 in circulating monocytes were evaluated. Hyperinsulinemia, associated with partial lipodystrophy, elevated RBP4, low adiponectin levels, and decreased expression of GLUT3 and GLUT4 were detected. The defects disclosed in this particular patient possibly explain, at least in part, the mechanisms underlying insulin resistance in patients undergoing BMT. It is not clear whether insulin resistance was caused by the drugs, the process itself, or the residual damage to the muscles and/or adipose tissue.
Research Interests: Kinetics, Inflammation, Adolescent, Medicine, Insulin Resistance, and 13 moreAdipose tissue, Humans, Child, Body Composition, Male, Pediatric, Adiponectin, Bone Marrow Transplantation, Monocytes, Glucose Tolerance Test, Gene Expression Regulation, Lipodystrophy, and Paediatrics and reproductive medicine
Research Interests: Research Design, Echocardiography, Cell therapy, Prospective studies, Humans, and 15 moreFemale, Feasibility Studies, Male, Peptides, Glycoproteins, Aged, Middle Aged, Pilot study, Bone Marrow Transplantation, Myocardial Infarction, Adult, Immunophenotyping, Coronary Circulation, Pilot Projects, and Cardiovascular medicine and haematology
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Background Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL) expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9) is correlated with... more
Background Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL) expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9) is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL) during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity. Methods The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays. Results Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p < 0.003, NGAL: p < 0.008 MMP-9/NGAL: p < 0.01)...
Research Interests: Cancer, Breast Cancer, Humans, Female, Disease Severity, and 13 moreAged, Middle Aged, Body mass index (BMI), Carcinoma, Adult, Acute Phase Proteins, Protein Binding, Case Control Studies, Matrix Metalloproteinase, Neutrophil Gelatinase Associated Lipocalin (NGAL), Breast Neoplasms, Invasive ductal carcinoma, and Peripheral blood
Endothelial progenitor cells (EPCs) and the recently described circulating fibrocytes (CFs) are strongly associated with tissue repair. We investigated the kinetics of both... more
Endothelial progenitor cells (EPCs) and the recently described circulating fibrocytes (CFs) are strongly associated with tissue repair. We investigated the kinetics of both &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;repair&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; progenitor cells in healthy athletes who participated in the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Spartahlon&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; ultradistance foot race (246 km continuous running exercise), which provides a unique model of inducing dramatic systemic inflammatory changes. Peripheral blood mononuclear cells (PBMCs) were isolated from 10 volunteer athletes, who completed successfully the race, before, at the end, and at 48 h post-race. EPCs and CFs were detected as endothelial colony-forming units (CFU-ECs) and as the number of adherent with a spindle-shaped morphology Collagen I(+) cells detected after 6-day culture of PBMCs, respectively. The marked increase of plasma levels of CRP, IL-6, SAA, MCP-1, IL-8, sVCAM-1, sICAM-1, thrombomodulin (sTM) and NT-pro-BNP at the end of race established acute inflammation and tissue injury. EPCs increased by nearly eleven-fold in peripheral blood at the end of the race from 44.5+/-2.5/ml to 494.6+/-27.9/ml and remained increased 428.5+/-31.5/ml at 48 h post-race (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001). The number of the fibrocytes cultured from PBMCs obtained before, at the end, and 48 h post-race did not reveal any significant difference. These findings indicate that bone marrow responses to acute inflammatory damage, induced by exhausting exercise, with a rapid release of EPCs but not CFs into circulation. Given the ability of EPCs to promote angiogenesis and vascular regeneration, we may suggest that this kind of cell mobilization may serve as a physiologic repair mechanism in acute inflammatory tissue injury.