Congestive heart failure(CHF)is defined as a cardiac dysfunction leading to low cardiac output and inadequate tissue perfusion.Intravenous positive inotropes are used to increase myocardial contractility in hospitaliz...Congestive heart failure(CHF)is defined as a cardiac dysfunction leading to low cardiac output and inadequate tissue perfusion.Intravenous positive inotropes are used to increase myocardial contractility in hospitalized patients with advanced heart failure.Milrinone is a phosphodiesterase Ⅲ inhibitor and used most commonly for inotropic effect.The well-known PROMISE study investigated the effects of milrinone on mortality in patients with severe CHF,and concluded that long-term therapy with milrinone increased morbidity and mortality armong patients with advanced CHF.Previous studies have suggested that phosphodiesterase inhibitors can have potential effects on inflammatory pathways.Hence,we hypothesized that milrinone may alter inflammatory gene expressions in cardiomyocytes,thus leading to adverse clinical outcomes.We used rat cardiomyocyte cell line H9 C2 and studied the impact of exposing cardiomyocytes to milrinone(10 μmol/L)for 24 hours on inflammatory gene expressions.RNA extracted from cultured cardiomyocytes was used for whole rat genome gene expression assay(41 000 genes).The following changes in inflammatory response-related gene expressions were discovered.Genes with increased expressions included:THBS2(+ 9.98),MMP2(+3.47),DDIT3(+2.39),and ADORA3(+3.5).Genes with decreased expressions were:SPP1(-5.28)and CD14(-2.05).We found that the above mentioned gene expression changes seem to indicate that milrinone may hinder the inflammatory process which may potentially lead to adverse clinical outcomes.However,further in vivo and clinical investigations will be needed to illustrate the clinical relevance of these gene expression changes induced by milrinone.展开更多
We report an apparently benign familial 9p subtelomere deletion identified using chromosome-arm-specific subtelomere probes in a patient with multiple congenital anomalies. Our experience demonstrated that the discove...We report an apparently benign familial 9p subtelomere deletion identified using chromosome-arm-specific subtelomere probes in a patient with multiple congenital anomalies. Our experience demonstrated that the discovery of a subtelomeric deletion and/or duplication does not always guarantee the identification of the etiology for the patient’s phenotype and a positive finding with subtelomere probes should always be followed by parental study with the same probe in order to distinguish a disease causing alteration from a benign familial polymorphism.展开更多
Fluorescence in situ hybridization (FISH) has become an important diagnostic tool as an adjunct to classical cytogenetics. FISH utilizes DNA probes comprised of specific nucleic acid sequences tagged with fluorescent ...Fluorescence in situ hybridization (FISH) has become an important diagnostic tool as an adjunct to classical cytogenetics. FISH utilizes DNA probes comprised of specific nucleic acid sequences tagged with fluorescent molecules to identify the number and location of specific DNA sequences in human cells. These probes can be used to determine various numerical and structural chromosomal aberrations, in many cases, gene dosage and/or structure alterations. Chromosomal abnormalities are responsible for a considerable number of birth defects, and more than 50% of spontaneous abortions. These numbers have been significantly higher since the advent of FISH technology that allows the detection of submicroscopic chromosome alterations. The clinic application of FISH technology in postnatal, prenatal, and preimplantation diagnoses has been playing an important role in the diagnosis and prevention of birth defects. As new technologies evolve, more and more new FISH techniques — such as subtelomeric FISH, multicolor FISH (M-FISH), comparative genomic hybridization (CGH), and microarray — are used in clinical diagnoses, the role of FISH technology in both research and clinical aspects of birth defects will surely continue to expand.展开更多
The most frequent chromosomal rearrangement reported in acute promyelocytic leukemia (APL) is t(15;17)(q22;q21). The t(15;17) generates the PML/RARA fusion gene that blocks the transcription of genes involved in myelo...The most frequent chromosomal rearrangement reported in acute promyelocytic leukemia (APL) is t(15;17)(q22;q21). The t(15;17) generates the PML/RARA fusion gene that blocks the transcription of genes involved in myeloid cell differentiation. A small number of simple and complex variants of the classical t(15;17) have been reported. We report two complex three-way translocation variants,t(3;17;15)(q27;q21;q22) and t(8;17;15)(q24.3;q12;q22) in which the PML/RARA fusion gene has been created on the derivative 15 chromosomes. Many of these variant translocations are suspected by conventional cytogenetics but need to be confirmed with additional molecular testing. We discuss the importance of supplementing conventional cytogenetic testing with FISH and RT-PCR to accurately diagnose APL variant patients.展开更多
基金fully supported by an intemal funding from the Department of Anesthesiology&Perioperative Medicine to Dr. Henry Liu
文摘Congestive heart failure(CHF)is defined as a cardiac dysfunction leading to low cardiac output and inadequate tissue perfusion.Intravenous positive inotropes are used to increase myocardial contractility in hospitalized patients with advanced heart failure.Milrinone is a phosphodiesterase Ⅲ inhibitor and used most commonly for inotropic effect.The well-known PROMISE study investigated the effects of milrinone on mortality in patients with severe CHF,and concluded that long-term therapy with milrinone increased morbidity and mortality armong patients with advanced CHF.Previous studies have suggested that phosphodiesterase inhibitors can have potential effects on inflammatory pathways.Hence,we hypothesized that milrinone may alter inflammatory gene expressions in cardiomyocytes,thus leading to adverse clinical outcomes.We used rat cardiomyocyte cell line H9 C2 and studied the impact of exposing cardiomyocytes to milrinone(10 μmol/L)for 24 hours on inflammatory gene expressions.RNA extracted from cultured cardiomyocytes was used for whole rat genome gene expression assay(41 000 genes).The following changes in inflammatory response-related gene expressions were discovered.Genes with increased expressions included:THBS2(+ 9.98),MMP2(+3.47),DDIT3(+2.39),and ADORA3(+3.5).Genes with decreased expressions were:SPP1(-5.28)and CD14(-2.05).We found that the above mentioned gene expression changes seem to indicate that milrinone may hinder the inflammatory process which may potentially lead to adverse clinical outcomes.However,further in vivo and clinical investigations will be needed to illustrate the clinical relevance of these gene expression changes induced by milrinone.
文摘We report an apparently benign familial 9p subtelomere deletion identified using chromosome-arm-specific subtelomere probes in a patient with multiple congenital anomalies. Our experience demonstrated that the discovery of a subtelomeric deletion and/or duplication does not always guarantee the identification of the etiology for the patient’s phenotype and a positive finding with subtelomere probes should always be followed by parental study with the same probe in order to distinguish a disease causing alteration from a benign familial polymorphism.
文摘Fluorescence in situ hybridization (FISH) has become an important diagnostic tool as an adjunct to classical cytogenetics. FISH utilizes DNA probes comprised of specific nucleic acid sequences tagged with fluorescent molecules to identify the number and location of specific DNA sequences in human cells. These probes can be used to determine various numerical and structural chromosomal aberrations, in many cases, gene dosage and/or structure alterations. Chromosomal abnormalities are responsible for a considerable number of birth defects, and more than 50% of spontaneous abortions. These numbers have been significantly higher since the advent of FISH technology that allows the detection of submicroscopic chromosome alterations. The clinic application of FISH technology in postnatal, prenatal, and preimplantation diagnoses has been playing an important role in the diagnosis and prevention of birth defects. As new technologies evolve, more and more new FISH techniques — such as subtelomeric FISH, multicolor FISH (M-FISH), comparative genomic hybridization (CGH), and microarray — are used in clinical diagnoses, the role of FISH technology in both research and clinical aspects of birth defects will surely continue to expand.
文摘The most frequent chromosomal rearrangement reported in acute promyelocytic leukemia (APL) is t(15;17)(q22;q21). The t(15;17) generates the PML/RARA fusion gene that blocks the transcription of genes involved in myeloid cell differentiation. A small number of simple and complex variants of the classical t(15;17) have been reported. We report two complex three-way translocation variants,t(3;17;15)(q27;q21;q22) and t(8;17;15)(q24.3;q12;q22) in which the PML/RARA fusion gene has been created on the derivative 15 chromosomes. Many of these variant translocations are suspected by conventional cytogenetics but need to be confirmed with additional molecular testing. We discuss the importance of supplementing conventional cytogenetic testing with FISH and RT-PCR to accurately diagnose APL variant patients.
