The main goal of the study was to identify a novel source of human multipotent cells, overcoming ethical issues involved in embryonic stem cell research and the limited availability of most adult stem cells. Amniotic ...The main goal of the study was to identify a novel source of human multipotent cells, overcoming ethical issues involved in embryonic stem cell research and the limited availability of most adult stem cells. Amniotic fluid cells （AFCs） are routinely obtained for prenatal diagnosis and can be expanded in vitro; nevertheless current knowledge about their origin and properties is limited. Twenty samples of AFCs were exposed in culture to adipogenic, osteogenic, neurogenic and myogenic media. Differentiation was evaluated using immunocytochemistry, RT-PCR and Western blotting. Before treatments, AFCs showed heterogeneous morphologies. They were negative for MyoD, Myf-5, MRF4, Myogenin and Desmin but positive for osteocalcin, PPARgamma2, GAP43, NSE, Nestin, MAP2, GFAP and beta tubulin III by RT-PCR. The cells expressed Oct-4, Rex-1 and Runx-1, which characterize the undifferentiated stem cell state. By immunocytochemistry they expressed neural-glial proteins, mesenchymal and epithelial markers. After culture, AFCs differentiated into adipocytes and osteoblasts when the predominant cellular component was fibroblastic. Early and late neuronal antigens were still present after 2 week culture in neural specific media even if no neuronal morphologies were detectable. Our results provide evidence that human amniotic fluid contains progenitor cells with multi-lineage potential showing stem and tissue-specific gene/protein presence for several lineages.展开更多
Introduction Epiploic appendagitis(EA)is an acute inflammation of the pedunculated mesenteric fat attached to the colonic surface,distinguished into two forms:primary EA,seemingly elicited by local ischaemic factors;a...Introduction Epiploic appendagitis(EA)is an acute inflammation of the pedunculated mesenteric fat attached to the colonic surface,distinguished into two forms:primary EA,seemingly elicited by local ischaemic factors;and secondary EA(SEA),elicited by the inflammation of the adjacent organs,with diverticulitis being the most common trigger[1].Few case series have described the association between SEA and inflammatory bowel disease(IBD);however,information about clinical,laboratory and imaging findings,outcomes,and the impact of IBD-specific therapy were not reported.We first report the case of a woman affected by ulcerative colitis(UC)who developed a SEA during vedolizumab therapy(Figure 1A).展开更多
BACKGROUND Immunosuppression(IS)therapy may contribute to cancer development.Some authors have proposed to reduce immunosuppression drugs dose in case of viral infections,in immunosuppression-related diseases,and in p...BACKGROUND Immunosuppression(IS)therapy may contribute to cancer development.Some authors have proposed to reduce immunosuppression drugs dose in case of viral infections,in immunosuppression-related diseases,and in patients undergoing radiotherapy.The present analysis reports the results of a systematic review on kidney transplant recipients undergoing immunosuppression and radiotherapy.AIM To define if it is necessary reduce immunosuppression drugs during radiotherapy.METHODS The literature search was based on three electronic databases(Pubmed,Scopus,and Web of Science)using selected keywords linked through the"AND"and"OR"Boolean operators to build specific strings for each electronic search engine.Two researchers independently screened the citations,and disagreement was resolved by discussion or through the intervention of a third author.The review was conducted and reported according to the PRISMA statement.Extracted data were narratively synthesized,and,where possible,frequencies,percentages,and ranges were calculated.RESULTS The literature search resulted in 147 citations.After abstracts screening,21 records were selected for full-text evaluation.Fifteen of these were excluded,leaving six papers considered suitable for analysis.There is still no clear evidence that withdrawing antimetabolites and/or calcineurin inhibitors and/or mammalian target of rapamycin-inhibitors,as opposed to continuing maintenance IS,improves patient survival in kidney transplant recipients with cancer undergoing radiotherapy.Only few retrospective studies on small cancer patient cohorts are available in this setting,but without comparison of different immunosuppression treatments.Even where immunosuppression therapy was described,patient survival seemed to be correlated only with cancer stage and type.CONCLUSION The results of this systematic review do not support the reduction of immunosuppression dose in patients undergoing radiotherapy.展开更多
Infantile pyknocytosis(IP) is a rare, self-limited neonatal haemolytic anaemia that may require multiple blood transfusions. Only a little more than 50 cases have been reported in the medical literature, and the great...Infantile pyknocytosis(IP) is a rare, self-limited neonatal haemolytic anaemia that may require multiple blood transfusions. Only a little more than 50 cases have been reported in the medical literature, and the great majority of them concerns term infants. The etiology of IP is not well understood; most likely it results from a transient extra-corpuscular factor, whose nature is unknown, transmitted from mother to child or, alternatively, from a deficiency of an anti-oxidative agent. We report the case of two preterm twins, one of which suffered from IP and developed severe anaemia at age 2 wk, while the other was unaffected. Although no specific agent was identified as the cause of anaemia and IP, we speculate that the transmission of an agent from mother to child was unlikely, as only twin one suffered from IP. Smelly greenish diarrhoea occurred just before the presentation of IP, suggesting that the same agent led to both the diarrhoea and the oxidative injury. Because IP may remain underdiagnosed, it should be considered in cases of early unexplained severe hemolytic anemia.展开更多
Hereditary aceruloplasminemia is a rare disease characterized by iron overload and neurodegeneration. Aceruloplasminemia is due to the absence/deficiency of ceruloplasmin, responsible for iron overload in liver, pancr...Hereditary aceruloplasminemia is a rare disease characterized by iron overload and neurodegeneration. Aceruloplasminemia is due to the absence/deficiency of ceruloplasmin, responsible for iron overload in liver, pancreas and other organs. We report the case of an Italian patient with hyperferritinemia, diabetes and hepatic iron excess, suspected to be affected by aceruloplasminemia. Patient underwent brain magnetic resonance imaging with and without paramagnetic medium contrast, which showed a hypointesity due to iron storage. The presence of a neurological disease and iron storage in the brain has led to assume the suspect of the aceruloplasminemia disease. We confirmed this hypothesis by the identification of a new nonsense mutation in exon 12 ceruloplasmin gene at codon 748, in homozygous status. When the diagnosis of ACP was established, the patient started chelation therapy with 75 mg/Kg/day deferiprone (DFP). Two months of starting therapy with DFP, serum ferritin values decreased to 693 ng/ml;the patient well tolerated the drug, and there have been no adverse events. Although rare, aceruloplasminemia should be considered in the differential diagnosis of unexplained iron overload.展开更多
Since the middle of 1990 s autologous stem cell trans-plantation has been the cornerstone for the treatment of young patients with multiple myeloma(MM). In the last decade the introduction of novel agents such as immu...Since the middle of 1990 s autologous stem cell trans-plantation has been the cornerstone for the treatment of young patients with multiple myeloma(MM). In the last decade the introduction of novel agents such as immunomodulatory drugs(IMi Ds) and proteasome inhibitors(PI), has dramatically changed the therapeutic scenario of this yet incurable disease. Due to the impressive results achieved with IMi Ds and PI both in terms of response rates and in terms of progression free and overall survival, and to the toxicity linked to high dose therapy and autologous stem cell transplantation(ASCT), a burning question nowadays is whether all young patients should be offered autotransplanta-tion up front or if this should be reserved for the time of relapse. This article provides a review of the data available regarding ASCT in MM and of the current opinion of the scientific community regarding its optimal timing.展开更多
Glutathionyl-haemoglobin (Hb-SSG) is a minor form of haemoglobin characterized by the presence of a disulfide bond between the β-93 cysteine residue and the thiol group of glutathione. Hb-SSG is naturally present in ...Glutathionyl-haemoglobin (Hb-SSG) is a minor form of haemoglobin characterized by the presence of a disulfide bond between the β-93 cysteine residue and the thiol group of glutathione. Hb-SSG is naturally present in the erythrocytes at levels comparable to those of glycated haemoglobin and can be measured by MALDI mass spectrometry on very small samples of erythrocytes from peripheral blood. Since Hb-SSG has been recognized as a sensitive biomarker of oxidative stress in several degenerative diseases (diabetes, hyperlipidemia, kidney disease) and in healthy workers exposed to glutathione-depleting toxic agents such as butadiene, we have measured for the first time the levels of Hb-SSG in two groups: healthy heavy cigarette smokers and overweight-obese. For both classes of subjects, the measured levels (6.4%±1.7%, n=30 for smokers;3.0%±0.8%, n=20 for overweight-obese) are in the upper 97thpercentile of those measured in the Italian general population. Levels in smokers show a small, yet statistically significant dependence on the level of smoking addiction (>20 cig./day vs. ￡20 cig./day: 7.0% ± 1.4% vs. 5.7% ± 1.1%;p < 0.05). This biomarker thus adds to those presently available to rationally assess the extent of biological damage caused by tobacco smoking.展开更多
Follicular lymphoma(FL)is the most common indolent non-Hodgkin lymphoma,accounting for 70%of cases in Western countries.Despite this unique name,FL is an extremely heterogeneous disease,both clinically and biologicall...Follicular lymphoma(FL)is the most common indolent non-Hodgkin lymphoma,accounting for 70%of cases in Western countries.Despite this unique name,FL is an extremely heterogeneous disease,both clinically and biologically.The basis of FL heterogeneity lies in the different biological pathways which can be activated,because of the variety of gene mutations that can occur.Today,there is a growing interest in the knowledge of these activated pathways,which is also testified by the presence of a new model that incorporates FL mutations to define patient’s prognosis(m7-FLIPI).These evaluations are also appealing because of the recent possibility of using“targeted therapies”.Targeted therapies are new tools,currently applicable in the setting of relapse/refractory(R/R)disease,where we can find a great variety of“chemo-free”combinations.As in other hematologic malignancies,“cellular therapy”enriches FL drug scenario,including T-cell dependent bispecific antibodies and chimeric antigen receptor(CAR)T-cell.Since FL heterogeneity is the basis of the difference in therapeutic efficacy and disease course among patients,the hope for the future is to understand FL biology more deeply,to better comprehend how to obtain more representative samples and pre-treatment prognostic information in order to individualize the treatment strategy as early as frontline therapy.展开更多
文摘The main goal of the study was to identify a novel source of human multipotent cells, overcoming ethical issues involved in embryonic stem cell research and the limited availability of most adult stem cells. Amniotic fluid cells （AFCs） are routinely obtained for prenatal diagnosis and can be expanded in vitro; nevertheless current knowledge about their origin and properties is limited. Twenty samples of AFCs were exposed in culture to adipogenic, osteogenic, neurogenic and myogenic media. Differentiation was evaluated using immunocytochemistry, RT-PCR and Western blotting. Before treatments, AFCs showed heterogeneous morphologies. They were negative for MyoD, Myf-5, MRF4, Myogenin and Desmin but positive for osteocalcin, PPARgamma2, GAP43, NSE, Nestin, MAP2, GFAP and beta tubulin III by RT-PCR. The cells expressed Oct-4, Rex-1 and Runx-1, which characterize the undifferentiated stem cell state. By immunocytochemistry they expressed neural-glial proteins, mesenchymal and epithelial markers. After culture, AFCs differentiated into adipocytes and osteoblasts when the predominant cellular component was fibroblastic. Early and late neuronal antigens were still present after 2 week culture in neural specific media even if no neuronal morphologies were detectable. Our results provide evidence that human amniotic fluid contains progenitor cells with multi-lineage potential showing stem and tissue-specific gene/protein presence for several lineages.
文摘Introduction Epiploic appendagitis(EA)is an acute inflammation of the pedunculated mesenteric fat attached to the colonic surface,distinguished into two forms:primary EA,seemingly elicited by local ischaemic factors;and secondary EA(SEA),elicited by the inflammation of the adjacent organs,with diverticulitis being the most common trigger[1].Few case series have described the association between SEA and inflammatory bowel disease(IBD);however,information about clinical,laboratory and imaging findings,outcomes,and the impact of IBD-specific therapy were not reported.We first report the case of a woman affected by ulcerative colitis(UC)who developed a SEA during vedolizumab therapy(Figure 1A).
文摘BACKGROUND Immunosuppression(IS)therapy may contribute to cancer development.Some authors have proposed to reduce immunosuppression drugs dose in case of viral infections,in immunosuppression-related diseases,and in patients undergoing radiotherapy.The present analysis reports the results of a systematic review on kidney transplant recipients undergoing immunosuppression and radiotherapy.AIM To define if it is necessary reduce immunosuppression drugs during radiotherapy.METHODS The literature search was based on three electronic databases(Pubmed,Scopus,and Web of Science)using selected keywords linked through the"AND"and"OR"Boolean operators to build specific strings for each electronic search engine.Two researchers independently screened the citations,and disagreement was resolved by discussion or through the intervention of a third author.The review was conducted and reported according to the PRISMA statement.Extracted data were narratively synthesized,and,where possible,frequencies,percentages,and ranges were calculated.RESULTS The literature search resulted in 147 citations.After abstracts screening,21 records were selected for full-text evaluation.Fifteen of these were excluded,leaving six papers considered suitable for analysis.There is still no clear evidence that withdrawing antimetabolites and/or calcineurin inhibitors and/or mammalian target of rapamycin-inhibitors,as opposed to continuing maintenance IS,improves patient survival in kidney transplant recipients with cancer undergoing radiotherapy.Only few retrospective studies on small cancer patient cohorts are available in this setting,but without comparison of different immunosuppression treatments.Even where immunosuppression therapy was described,patient survival seemed to be correlated only with cancer stage and type.CONCLUSION The results of this systematic review do not support the reduction of immunosuppression dose in patients undergoing radiotherapy.
文摘Infantile pyknocytosis(IP) is a rare, self-limited neonatal haemolytic anaemia that may require multiple blood transfusions. Only a little more than 50 cases have been reported in the medical literature, and the great majority of them concerns term infants. The etiology of IP is not well understood; most likely it results from a transient extra-corpuscular factor, whose nature is unknown, transmitted from mother to child or, alternatively, from a deficiency of an anti-oxidative agent. We report the case of two preterm twins, one of which suffered from IP and developed severe anaemia at age 2 wk, while the other was unaffected. Although no specific agent was identified as the cause of anaemia and IP, we speculate that the transmission of an agent from mother to child was unlikely, as only twin one suffered from IP. Smelly greenish diarrhoea occurred just before the presentation of IP, suggesting that the same agent led to both the diarrhoea and the oxidative injury. Because IP may remain underdiagnosed, it should be considered in cases of early unexplained severe hemolytic anemia.
文摘Hereditary aceruloplasminemia is a rare disease characterized by iron overload and neurodegeneration. Aceruloplasminemia is due to the absence/deficiency of ceruloplasmin, responsible for iron overload in liver, pancreas and other organs. We report the case of an Italian patient with hyperferritinemia, diabetes and hepatic iron excess, suspected to be affected by aceruloplasminemia. Patient underwent brain magnetic resonance imaging with and without paramagnetic medium contrast, which showed a hypointesity due to iron storage. The presence of a neurological disease and iron storage in the brain has led to assume the suspect of the aceruloplasminemia disease. We confirmed this hypothesis by the identification of a new nonsense mutation in exon 12 ceruloplasmin gene at codon 748, in homozygous status. When the diagnosis of ACP was established, the patient started chelation therapy with 75 mg/Kg/day deferiprone (DFP). Two months of starting therapy with DFP, serum ferritin values decreased to 693 ng/ml;the patient well tolerated the drug, and there have been no adverse events. Although rare, aceruloplasminemia should be considered in the differential diagnosis of unexplained iron overload.
文摘Since the middle of 1990 s autologous stem cell trans-plantation has been the cornerstone for the treatment of young patients with multiple myeloma(MM). In the last decade the introduction of novel agents such as immunomodulatory drugs(IMi Ds) and proteasome inhibitors(PI), has dramatically changed the therapeutic scenario of this yet incurable disease. Due to the impressive results achieved with IMi Ds and PI both in terms of response rates and in terms of progression free and overall survival, and to the toxicity linked to high dose therapy and autologous stem cell transplantation(ASCT), a burning question nowadays is whether all young patients should be offered autotransplanta-tion up front or if this should be reserved for the time of relapse. This article provides a review of the data available regarding ASCT in MM and of the current opinion of the scientific community regarding its optimal timing.
文摘Glutathionyl-haemoglobin (Hb-SSG) is a minor form of haemoglobin characterized by the presence of a disulfide bond between the β-93 cysteine residue and the thiol group of glutathione. Hb-SSG is naturally present in the erythrocytes at levels comparable to those of glycated haemoglobin and can be measured by MALDI mass spectrometry on very small samples of erythrocytes from peripheral blood. Since Hb-SSG has been recognized as a sensitive biomarker of oxidative stress in several degenerative diseases (diabetes, hyperlipidemia, kidney disease) and in healthy workers exposed to glutathione-depleting toxic agents such as butadiene, we have measured for the first time the levels of Hb-SSG in two groups: healthy heavy cigarette smokers and overweight-obese. For both classes of subjects, the measured levels (6.4%±1.7%, n=30 for smokers;3.0%±0.8%, n=20 for overweight-obese) are in the upper 97thpercentile of those measured in the Italian general population. Levels in smokers show a small, yet statistically significant dependence on the level of smoking addiction (>20 cig./day vs. ￡20 cig./day: 7.0% ± 1.4% vs. 5.7% ± 1.1%;p < 0.05). This biomarker thus adds to those presently available to rationally assess the extent of biological damage caused by tobacco smoking.
文摘Follicular lymphoma(FL)is the most common indolent non-Hodgkin lymphoma,accounting for 70%of cases in Western countries.Despite this unique name,FL is an extremely heterogeneous disease,both clinically and biologically.The basis of FL heterogeneity lies in the different biological pathways which can be activated,because of the variety of gene mutations that can occur.Today,there is a growing interest in the knowledge of these activated pathways,which is also testified by the presence of a new model that incorporates FL mutations to define patient’s prognosis(m7-FLIPI).These evaluations are also appealing because of the recent possibility of using“targeted therapies”.Targeted therapies are new tools,currently applicable in the setting of relapse/refractory(R/R)disease,where we can find a great variety of“chemo-free”combinations.As in other hematologic malignancies,“cellular therapy”enriches FL drug scenario,including T-cell dependent bispecific antibodies and chimeric antigen receptor(CAR)T-cell.Since FL heterogeneity is the basis of the difference in therapeutic efficacy and disease course among patients,the hope for the future is to understand FL biology more deeply,to better comprehend how to obtain more representative samples and pre-treatment prognostic information in order to individualize the treatment strategy as early as frontline therapy.
