Purpose: To compare the activities of acid phosphatase, N-acetyl-β-glu-cosaminidase and a- mannosidase in cultured retinal pigment epithelium (RPE)and glial cells of Royal College of Surgeons (RCS) rat with those in ...Purpose: To compare the activities of acid phosphatase, N-acetyl-β-glu-cosaminidase and a- mannosidase in cultured retinal pigment epithelium (RPE)and glial cells of Royal College of Surgeons (RCS) rat with those in Long Evans(LE).Methods: The cultured RPE and glial cells of RCS and LE rat were plated into thesame 96 well microtitre, and the biochemical method in microsystem were usedfor enzyme assays.Results: The activities of acid phosphatase and N-acetyl- β-glucosaminidase arehigher by, respectively, 30% and 46% in cultured RPE of RCS rat than LE rat.The activity of a- mannosidase has no significant difference. The activities of 3enzymes in the retinal glial cells derived from RCS rats are higher than LE rat by43% to 77%.Conclusion: These results suggest that the high activities of lysosomal enzymes inRCS RPE and glial cells may play an important role in the pathogenesis of retinaldystrophy. Eye Science 1996; 12:20-27.展开更多
Macrophages (M) are the major target cells in endotoxin (bacterial lipopolysaccharide, LPS) stimulation. Endotoxin triggers the inflammatory cells to release mediators, including tumor necrosis factor (TNF). This is o...Macrophages (M) are the major target cells in endotoxin (bacterial lipopolysaccharide, LPS) stimulation. Endotoxin triggers the inflammatory cells to release mediators, including tumor necrosis factor (TNF). This is one possible reason for endotoxin shock and organ damage. Polydatin (PD) is a component of the rhizoma of Polygonum cuspidatum,a Chinese herb medicine. our previous studies showed that it attenuated TNF and NAG elevations in experimental intestinal ischemia-reperfusion injury and endotoxin shock. The present study is designed in vitro to demonstrate whether the attenuation was due to the effect of PD. Mice peritoneal M were isolated and incubated in 5% CO2in air at 37℃. Different doses of polydatin were added respectively into the wells before and after LPS stimulation. Concentrations of TNF and N-acetyl-β-D-glucosaminidase (NAG, a lysosomal enzyme) in the supernatants were determined. The results showed that PD decreased the levels of TNF and NAG in the supernatant of LPS- stimulated M with statistically significant differences. In 0. 50, 0. 82 and 1. 95 mmol/L PD -pretreated groups, LPS caused lower TNF production, 1. 26±0. 24, 0. 71 ±0. 34, and 0. 78± 0. 32 U/ml,respectively, vs 2. 17± 0. 24 U/ml of the untreated control. The NAG released was also much less, 3. 52± 0. 13, 2. 03± 0.30 and 2. 28± 0. 40 U/L,respectively,vs 4. 58±0. 18 U/L of untreated control. In the supernatants of M stimulated by LPS for 1 h, followed by addition of PD for 1 h, TNF produced was also less in PD- pretreated groups: 1.51±0. 47, 1. 43±0. 43 vs 2. 17± 0. 23 U/ml; while NAG levels decreased to 2. 89±0. 23, 2. 68±0. 16., and 2. 83± 0. 13 U/L vs 4. 58±0. 18 of control (P < 0. 001). It is concluded that PD inhibits TNF and NAG release from endotoxin-stimulated peritoneal macrophages in mice.展开更多
BACKGROUND Fabry disease(FD)is a rare X-linked lysosomal storage disease caused by a deficiency of the enzymeα-galactosidase A.CASE SUMMARY Herein,we analyzed a four-generation Chinese family.The proband is a 57-year...BACKGROUND Fabry disease(FD)is a rare X-linked lysosomal storage disease caused by a deficiency of the enzymeα-galactosidase A.CASE SUMMARY Herein,we analyzed a four-generation Chinese family.The proband is a 57-yearold woman who was diagnosed with left ventricular hypertrophy and atrial fibrillation 7 years ago.Echocardiography showed an end-diastolic diameter of the interventricular septum of 19.9 mm,left ventricular end-diastolic diameter of 63.1 mm,and moderate-to-severe mitral regurgitation.Cardiac magnetic resonance indicated an enlarged left heart and right atrium,decreased left ventricular systolic and diastolic function,a left ventricular ejection fraction of 20%,and thickening of the left ventricular septum.In March 2019,gene and enzyme activity tests confirmed the diagnosis of FD.Her son was diagnosed with FD after gene and enzyme activity assay,and was prescribed agalsidase-βfor enzyme replacement therapy in July 2020.Two sisters of the proband were also diagnosed with FD by genetic testing.Both of them had a history of atrial fibrillation.CONCLUSION A novel mutation was identified in a Chinese family with FD,in which the male patient had a low level of enzyme activity,early-onset,and severe organ involvement.Comprehensive analysis of clinical phenotype genetic testing and enzyme activity testing helped in the diagnosis and treatment of this FD family.展开更多
To the Editor:The mucopolysaccharidosis (MPS) disorders are a group of rare,inherited lysosomal storage disorders in which progressive cellular accumulation of glycosaminoglycans (GAGs) caused by lysosomal enzyme defi...To the Editor:The mucopolysaccharidosis (MPS) disorders are a group of rare,inherited lysosomal storage disorders in which progressive cellular accumulation of glycosaminoglycans (GAGs) caused by lysosomal enzyme deficiency,leads to multi-organ dysfunction.Each kind of MPS disorder (I-IX) is caused by deficiency of a specific lysosomal enzyme and subsequent degraded GAGs fragments increase in urine,blood,and cerebral spinal fluid.展开更多
Fabry Disease (FD) is a rare lysosomal storage disorder characterized by α-galactosidase A (α-Gal A) enzyme deficiency, resulting in glycosphingolipid accumulation. Its clinical spectrum ranges from severe classical...Fabry Disease (FD) is a rare lysosomal storage disorder characterized by α-galactosidase A (α-Gal A) enzyme deficiency, resulting in glycosphingolipid accumulation. Its clinical spectrum ranges from severe classical to milder nonclassical or late-onset phenotypes. Renal involvement, termed Fabry Nephropathy (FN), can vary from mild proteinuria to kidney failure. FN diagnosis, especially in nonclassical cases with a genetic Variant of Unknown Significance (VUS) in the GLA gene, poses challenges. Measurement of plasma lyso-Gb3 levels is gaining importance in FN diagnosis, while renal biopsy with electron microscopy remains the gold standard in equivocal cases. Treatment options include Enzyme Replacement Therapy (ERT) and chaperone therapy, demanding careful candidate selection due to high treatment costs. Research has predominantly focused on classical FD, revealing modest treatment benefits. However, evidence for treating patients, especially females, with milder nonclassical or late-onset phenotypes is scarce, emphasizing the necessity for placebo-controlled clinical trials in these subgroups. Meanwhile, participation in global FD registries can improve our understanding of disease management. Case Presentation: A woman in her late sixties presented with moderate chronic kidney disease, mild proteinuria, and microscopic hematuria. Her family history included a prevalence of renal, cardiac and cerebrovascular diseases. Kidney biopsy revealed characteristic myelin figures and zebra bodies in podocytes, strongly suggestive of FN. Genetic analysis identified a VUS in the GLA gene (c.655A > C, p.Ile219Leu), introducing diagnostic uncertainty. Further investigations revealed severe cardiac involvement. Considering the recurring difficulty presented by the finding of a VUS in the GLA gene during FN assessments, along with the uncertainty regarding the need for treatment in nonclassical or late-onset FD phenotypes, especially in women, this case becomes a central focus for a thorough review of the literature. This rev展开更多
Gaucher disease is the prototypical lysosomal storage disease.It results from the accumulation of undegrad-ed glucosylceramide in the reticuloendothelial system of the bone marrow,spleen and liver due to deficiency of...Gaucher disease is the prototypical lysosomal storage disease.It results from the accumulation of undegrad-ed glucosylceramide in the reticuloendothelial system of the bone marrow,spleen and liver due to deficiency of the enzyme glucocerebrosidase.This leads to he-matologic,visceral and skeletal maifestions.Build up of glucosylceramide in the liver and spleen results in hepatosplenomegaly.The normal bone marrow is re-placed by the accumulating substrate leading to many of the hematologic signs including anemia.The visceral and skeletal manifestations can be visualized with vari-ous imaging modalities including radiography,com-puted tomography,magnetic resonance imaging(MRI)and radionuclide scanning.Prior to the development of enzyme replacement therapy,treatment was only sup-portive.However,once intravenous enzyme replace-ment therapy became available in the 1990s it quickly became the standard of care.Enzyme replacement therapy leads to improvement in all manifestations.Thevisceral and hematologic manifestations respond more quickly usually within a few months or years.The skel-etal manifestations take much longer,usually several years,to show improvement.In recent years newer treatment strategies,such as substrate reduction thera-py,have been under investigation.Imaging plays a key role in both initial diagnosis and routine monitoring of patient on treatment particularly volumetric MRI of the liver and spleen and MRI of the femora for evaluating bone marrow disease burden.展开更多
文摘Purpose: To compare the activities of acid phosphatase, N-acetyl-β-glu-cosaminidase and a- mannosidase in cultured retinal pigment epithelium (RPE)and glial cells of Royal College of Surgeons (RCS) rat with those in Long Evans(LE).Methods: The cultured RPE and glial cells of RCS and LE rat were plated into thesame 96 well microtitre, and the biochemical method in microsystem were usedfor enzyme assays.Results: The activities of acid phosphatase and N-acetyl- β-glucosaminidase arehigher by, respectively, 30% and 46% in cultured RPE of RCS rat than LE rat.The activity of a- mannosidase has no significant difference. The activities of 3enzymes in the retinal glial cells derived from RCS rats are higher than LE rat by43% to 77%.Conclusion: These results suggest that the high activities of lysosomal enzymes inRCS RPE and glial cells may play an important role in the pathogenesis of retinaldystrophy. Eye Science 1996; 12:20-27.
文摘Macrophages (M) are the major target cells in endotoxin (bacterial lipopolysaccharide, LPS) stimulation. Endotoxin triggers the inflammatory cells to release mediators, including tumor necrosis factor (TNF). This is one possible reason for endotoxin shock and organ damage. Polydatin (PD) is a component of the rhizoma of Polygonum cuspidatum,a Chinese herb medicine. our previous studies showed that it attenuated TNF and NAG elevations in experimental intestinal ischemia-reperfusion injury and endotoxin shock. The present study is designed in vitro to demonstrate whether the attenuation was due to the effect of PD. Mice peritoneal M were isolated and incubated in 5% CO2in air at 37℃. Different doses of polydatin were added respectively into the wells before and after LPS stimulation. Concentrations of TNF and N-acetyl-β-D-glucosaminidase (NAG, a lysosomal enzyme) in the supernatants were determined. The results showed that PD decreased the levels of TNF and NAG in the supernatant of LPS- stimulated M with statistically significant differences. In 0. 50, 0. 82 and 1. 95 mmol/L PD -pretreated groups, LPS caused lower TNF production, 1. 26±0. 24, 0. 71 ±0. 34, and 0. 78± 0. 32 U/ml,respectively, vs 2. 17± 0. 24 U/ml of the untreated control. The NAG released was also much less, 3. 52± 0. 13, 2. 03± 0.30 and 2. 28± 0. 40 U/L,respectively,vs 4. 58±0. 18 U/L of untreated control. In the supernatants of M stimulated by LPS for 1 h, followed by addition of PD for 1 h, TNF produced was also less in PD- pretreated groups: 1.51±0. 47, 1. 43±0. 43 vs 2. 17± 0. 23 U/ml; while NAG levels decreased to 2. 89±0. 23, 2. 68±0. 16., and 2. 83± 0. 13 U/L vs 4. 58±0. 18 of control (P < 0. 001). It is concluded that PD inhibits TNF and NAG release from endotoxin-stimulated peritoneal macrophages in mice.
基金Supported by Key Research and Development Program of Zhejiang Province,No.2019C03022.
文摘BACKGROUND Fabry disease(FD)is a rare X-linked lysosomal storage disease caused by a deficiency of the enzymeα-galactosidase A.CASE SUMMARY Herein,we analyzed a four-generation Chinese family.The proband is a 57-yearold woman who was diagnosed with left ventricular hypertrophy and atrial fibrillation 7 years ago.Echocardiography showed an end-diastolic diameter of the interventricular septum of 19.9 mm,left ventricular end-diastolic diameter of 63.1 mm,and moderate-to-severe mitral regurgitation.Cardiac magnetic resonance indicated an enlarged left heart and right atrium,decreased left ventricular systolic and diastolic function,a left ventricular ejection fraction of 20%,and thickening of the left ventricular septum.In March 2019,gene and enzyme activity tests confirmed the diagnosis of FD.Her son was diagnosed with FD after gene and enzyme activity assay,and was prescribed agalsidase-βfor enzyme replacement therapy in July 2020.Two sisters of the proband were also diagnosed with FD by genetic testing.Both of them had a history of atrial fibrillation.CONCLUSION A novel mutation was identified in a Chinese family with FD,in which the male patient had a low level of enzyme activity,early-onset,and severe organ involvement.Comprehensive analysis of clinical phenotype genetic testing and enzyme activity testing helped in the diagnosis and treatment of this FD family.
基金This work was supported by grants from the National Natural Science Foundation of China (Nos.81770875, 81702156, 81572639)the Science and Technology Department of Sichuan Province (No.2018SZ0142)+1 种基金Postdoctoral Science Foundation of China (No.2017M61060)the Sichuan University (Nos. 2018SCUH0093, 2017SCU12038).
文摘To the Editor:The mucopolysaccharidosis (MPS) disorders are a group of rare,inherited lysosomal storage disorders in which progressive cellular accumulation of glycosaminoglycans (GAGs) caused by lysosomal enzyme deficiency,leads to multi-organ dysfunction.Each kind of MPS disorder (I-IX) is caused by deficiency of a specific lysosomal enzyme and subsequent degraded GAGs fragments increase in urine,blood,and cerebral spinal fluid.
文摘Fabry Disease (FD) is a rare lysosomal storage disorder characterized by α-galactosidase A (α-Gal A) enzyme deficiency, resulting in glycosphingolipid accumulation. Its clinical spectrum ranges from severe classical to milder nonclassical or late-onset phenotypes. Renal involvement, termed Fabry Nephropathy (FN), can vary from mild proteinuria to kidney failure. FN diagnosis, especially in nonclassical cases with a genetic Variant of Unknown Significance (VUS) in the GLA gene, poses challenges. Measurement of plasma lyso-Gb3 levels is gaining importance in FN diagnosis, while renal biopsy with electron microscopy remains the gold standard in equivocal cases. Treatment options include Enzyme Replacement Therapy (ERT) and chaperone therapy, demanding careful candidate selection due to high treatment costs. Research has predominantly focused on classical FD, revealing modest treatment benefits. However, evidence for treating patients, especially females, with milder nonclassical or late-onset phenotypes is scarce, emphasizing the necessity for placebo-controlled clinical trials in these subgroups. Meanwhile, participation in global FD registries can improve our understanding of disease management. Case Presentation: A woman in her late sixties presented with moderate chronic kidney disease, mild proteinuria, and microscopic hematuria. Her family history included a prevalence of renal, cardiac and cerebrovascular diseases. Kidney biopsy revealed characteristic myelin figures and zebra bodies in podocytes, strongly suggestive of FN. Genetic analysis identified a VUS in the GLA gene (c.655A > C, p.Ile219Leu), introducing diagnostic uncertainty. Further investigations revealed severe cardiac involvement. Considering the recurring difficulty presented by the finding of a VUS in the GLA gene during FN assessments, along with the uncertainty regarding the need for treatment in nonclassical or late-onset FD phenotypes, especially in women, this case becomes a central focus for a thorough review of the literature. This rev
文摘Gaucher disease is the prototypical lysosomal storage disease.It results from the accumulation of undegrad-ed glucosylceramide in the reticuloendothelial system of the bone marrow,spleen and liver due to deficiency of the enzyme glucocerebrosidase.This leads to he-matologic,visceral and skeletal maifestions.Build up of glucosylceramide in the liver and spleen results in hepatosplenomegaly.The normal bone marrow is re-placed by the accumulating substrate leading to many of the hematologic signs including anemia.The visceral and skeletal manifestations can be visualized with vari-ous imaging modalities including radiography,com-puted tomography,magnetic resonance imaging(MRI)and radionuclide scanning.Prior to the development of enzyme replacement therapy,treatment was only sup-portive.However,once intravenous enzyme replace-ment therapy became available in the 1990s it quickly became the standard of care.Enzyme replacement therapy leads to improvement in all manifestations.Thevisceral and hematologic manifestations respond more quickly usually within a few months or years.The skel-etal manifestations take much longer,usually several years,to show improvement.In recent years newer treatment strategies,such as substrate reduction thera-py,have been under investigation.Imaging plays a key role in both initial diagnosis and routine monitoring of patient on treatment particularly volumetric MRI of the liver and spleen and MRI of the femora for evaluating bone marrow disease burden.
