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Storage Disease (storage + disease)
Kinds of Storage Disease Terms modified by Storage Disease Selected AbstractsSeventh International Symposium on Lysosomal Storage DiseasesACTA PAEDIATRICA, Issue 2008Johannes Aerts No abstract is available for this article. [source] Storage diseases of apples (preharvest application)EPPO BULLETIN, Issue 1 2003Article first published online: 11 APR 200 First page of article [source] Advances in the treatment of lysosomal storage diseaseDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2001J E Wraith MB ChB FRCP FRCPCH First page of article [source] Lysosomal storage disease in Sida carpinifolia toxicosis: an induced mannosidosis in horsesEQUINE VETERINARY JOURNAL, Issue 5 2003A. P. LORETTI Summary Reasons for performing study: This study reports a neurological disease unrecognised until now in ponies in southern Brazil. Hypothesis: Epidemiological data strongly suggests that the ingestion of Sida carpinifolia is involved in the aetiology. We tested the hypothesis that it is an acquired lyosomal storage disease. Methods: Following the death of 3 ponies, all ponies from the premises were closely monitored; epidemiological data and clinical findings carefully recorded. Fragments of several organs, including CNS, were fixed in neutral formalin and embedded in paraffin-wax. Sections were stained with haematoxylin and eosin. Representative sections of the cerebellum and trigeminal ganglia were submitted to lectin histochemical procedures. Results: The neurological disorder, characterised by stiff gait, muscle tremors, abdominal pain and death, was observed on a farm with 3 hectares of pasture. Three of 11 ponies died 15,20 days after they had been introduced into a new paddock heavily infested by the plant Sida carpinifolia. No significant gross lesions were observed. The main histological findings included multiple cytoplasmatic vacuoles in swollen neurones in the brain, cerebellum, spinal cord, autonomic ganglia (trigeminal and celiac ganglia), and submucosal and myenteric plexus of the intestines. In the kidneys, there was marked vacuolation of the proximal convoluted tubular cells. Sections of cerebellum and trigeminal ganglion were submitted to lectin histochemistry. The vacuoles in different cerebellar and ganglion cells reacted strongly to the following lectins: Concanavalia ensiformis, Triticum vulgaris and succinylated- Triticum vulgaris. Conclusions: The pattern of staining coincides with that of both swainsonine toxicosis and inherited mannosidosis reports. The histopathological changes were similar to those described in S. carpinifolia spontaneous and experimental poisoning in goats. This disease seems to be similar to Swainsona, Oxytropis and Astragalus toxicosis. Potential relevance: S. carpinifolia should be evaluated as a possible cause in the diagnosis of equine neuropathies. [source] Treatment of adult storage disease: cost versus benefitEUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2009B. Buehler No abstract is available for this article. [source] Glycolipid receptor depletion as an approach to specific antimicrobial therapyFEMS MICROBIOLOGY LETTERS, Issue 1 2006Majlis Svensson Abstract Mucosal pathogens recognize glycoconjugate receptors at the site of infection, and attachment is an essential first step in disease pathogenesis. Inhibition of attachment may prevent disease, and several approaches have been explored. This review discusses the prevention of bacterial attachment and disease by agents that modify the glycosylation of cell surface glycoconjugates. Glycosylation inhibitors were tested in the urinary tract infection model, where P-fimbriated Escherichia coli rely on glycosphingolipid receptors for attachment and tissue attack. N -butyldeoxynojirimycin blocked the expression of glucosylceramide-derived glycosphingolipids and attachment was reduced. Bacterial persistence in the kidneys was impaired and the inflammatory response was abrogated. N -butyldeoxynojirimycin was inactive against strains which failed to engage these receptors, including type 1 fimbriated or nonadhesive strains. In vivo attachment has been successfully prevented by soluble receptor analogues, but there is little clinical experience of such inhibitors. Large-scale synthesis of complex carbohydrates, which could be used as attachment inhibitors, remains a technical challenge. Antibodies to bacterial lectins involved in attachment may be efficient inhibitors, and fimbrial vaccines have been developed. Glycosylation inhibitors have been shown to be safe and efficient in patients with lipid storage disease and might therefore be tested in urinary tract infection. This approach differs from current therapies, including antibiotics, in that it targets the pathogens which recognize these receptors. [source] A novel aspartylglucosaminuria mutation affects translocation of aspartylglucosaminidase,,HUMAN MUTATION, Issue 4 2004Jani Saarela Abstract The AGA gene is mutated in patients with aspartylglucosaminuria (AGU), a lysosomal storage disease enriched in the Finnish population. The disease mechanism of AGU and the biochemistry and cell biology of the lysosomal aspartylglucosaminidase (AGA) enzyme are well characterized. Here, we have investigated a novel AGU mutation found in a Finnish patient. The mutation was detected as a compound heterozygote with the Finnish major mutation in the other allele. The novel point mutation, c.44T>G, causes the L15R amino acid substitution in the signal sequence of the AGA enzyme. The mutated AGA enzyme was here analyzed by over expression in BHK and COS-1 cells. The L15R AGA protein was only faintly detectable by immunofluorescence analysis and observed in the endoplasmic reticulum. Metabolic labeling and immunoprecipitation revealed only a small amount of AGA polypeptides but the specific activity of the mutant enzyme was surprisingly high, 37% of the wild type. The amino acid substitution probably affects translocation of AGA polypeptides by altering a critical hydrophobic core structure of the signal sequence. It appears that the small amounts of active enzyme are not able to reach the lysosomes thus explaining the development of AGU disease in the patient. © 2004 Wiley-Liss, Inc. [source] Analysis of the glucocerebrosidase gene and mutation profile in 144 Italian gaucher patients,,HUMAN MUTATION, Issue 3 2002Mirella Filocamo Abstract Gaucher disease (GD), the most prevalent lysosomal storage disease characterized by a remarkable degree of clinical variability, results from deleterious mutations in the glucocerebrosidase gene (GBA). In this paper we report the molecular characterization of 144 unrelated Italian GD patients with the three types of the disease. The allelic frequencies of Italians are reported and the mutation profile is analyzed. Besides the common N370S, L444P, RecNciI, G202R, IVS2+1G>A, D409H, F213I mutations, the different molecular strategies, used for the mutation detection, identified the rare N107L, R131C, R170C, R170P, N188S, S196P, R285C, R285H, W312C, D399N, A446P, IVS10-1G>A, Rec,55, total gene deletion, as well as 12 mutant alleles that were exclusively present in the Italian population until now: the previously reported R353G, N370S+S488P mosaicism, IVS8(-11delC)-14T>A), Rec I, Y418C, and the seven novel alleles D127X, P159T, V214X, T231R, L354X, H451R, and G202R+M361I. The wide phenotypic differences observed within the genotypic groups as well as between siblings implicate a significant contribution of other modifying genetic and/or non-genetic factors and claim a comprehensive valuation of the patient including clinical., biochemical and molecular investigations for prognosis, appropriate interventive therapy and reliable genetic counseling. © 2002 Wiley-Liss, Inc. [source] The expanding clinical spectrum of Anderson,Fabry disease: a challenge to diagnosis in the novel era of enzyme replacement therapyJOURNAL OF INTERNAL MEDICINE, Issue 6 2004A. C. Hauser Abstract. Anderson,Fabry disease is an X-linked recessive lysosomal storage disease resulting from deficient ,-galactosidase A activity. The conception of the disease has changed within the last decade. Studies of the last years have shown that the disease is not limited to the classical full-blown manifestation in affected males, which is well known since more than a century, but may also occur in carrier females. The phenomenology may differ in severity and kind of organ manifestation. Cardiac and renal variants with solely disease manifestation of these organs have also been described in an increasing number. It is likely that a spectrum exists regarding ,-galactosidase A activity in both genders on the one hand, and an additional one regarding the severity and the number of organs affected on the other. The purpose of this review is to sharpen physicians' perception of this disease. Early and accurate diagnosis is mandatory considering that this disorder is now, after introduction of the novel enzyme replacement therapy, a treatable disease. [source] Innate and adaptive immune activation in the brain of MPS IIIB mouse modelJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2009Julianne DiRosario Abstract Mucopolysaccharidosis (MPS) IIIB is a lysosomal storage disease with severe neurological manifestations due to ,- N -acetylglucosaminidase (NaGlu) deficiency. The mechanism of neuropathology in MPS IIIB is unclear. This study investigates the role of immune responses in neurological disease of MPS IIIB in mice. By means of gene expression microarrays and real-time quantitative reverse transcriptase,polymerase chain reaction, we demonstrated significant up-regulation of numerous immune-related genes in MPS IIIB mouse brain involving a broad range of immune cells and molecules, including T cells, B cells, microglia/macrophages, complement, major histocompatibility complex class I, immunoglobulin, Toll-like receptors, and molecules essential for antigen presentation. The significantly enlarged spleen and lymph nodes in MPS IIIB mice were due to an increase in splenocytes/lymphocytes, and functional assays indicated that the T cells were activated. An autoimmune component to the disease was further suggested by the presence of putative autoantigen or autoantigens in brain extracts that reacted specifically with serum IgG from MPS IIIB mice. We also demonstrated for the first time that immunosuppression with prednisolone alone can significantly slow the central nervous system disease progression. Our data indicate that immune responses contribute greatly to the neuropathology of MPS IIIB and should be considered as an adjunct treatment in future therapeutic developments for optimal therapeutic effect. © 2008 Wiley-Liss, Inc. [source] Novel fibrinogen mutation ,314Thr,Pro (fibrinogen AI duPont) associated with hepatic fibrinogen storage disease and hypofibrinogenaemiaLIVER INTERNATIONAL, Issue 10 2010Stephen O. Brennan Abstract Mutation in fibrinogen genes may lead to quantitative or qualitative disorders that result in bleeding, thrombosis or hepatic fibrinogen storage disease. Only three mutations in the fibrinogen , gene have been identified that cause hepatic endoplasmic reticulum storage of mutant fibrinogen. To investigate the possibility of hepatic fibrinogen storage disease in a 4-year-old male with persistently elevated serum aminotransferases and preserved synthetic function except for a prolonged INR. After informed consent, liver and blood samples were obtained. Liver sections were examined by light microscopy, anti-fibrinogen immunolabelling and electron microscopy. Purified fibrinogen was analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and reverse phase high performance liquid chromatography; DNA sequencing was performed using a BigDye Terminator (v. 3.1) cycle sequencing kit. Four-year-old male with persistently elevated transaminases with an INR 1.5 but otherwise normal synthetic function. Fibrinogen activity and thrombin clotting time were abnormal at 0.47 g/L and 46 s respectively. Hepatic histological examination revealed portal inflammatory infiltrates with bridging fibrosis. Clumped eosinophilic material was observed in hepatocytes that was immunoreactive to fibrinogen antisera. Ultrastructural examination showed cytoplasmic inclusions arrayed in fingerprint-like patterns. DNA sequence analysis revealed heterozygosity for a novel ,314Thr ,Pro mutation (fibrinogen AI duPont) in the fibrinogen , gene. Protein analyses showed normal patterns of A,, B, and , chains suggesting that the variant , allele was not expressed in plasma fibrinogen. We describe only the fourth mutation to be identified, ,314Thr,Pro (fibrinogen AI duPont), giving rise to hypofibrinogenaemia and hepatic fibrinogen storage disease. [source] Polyglutamine disease: Recent advances in the neuropathology of dentatorubral-pallidoluysian atrophyNEUROPATHOLOGY, Issue 4 2006Mitsunori Yamada Polyglutamine diseases are hereditary neurodegenerative disorders that are caused by the expansion of a CAG repeat in the causative genes. They comprise at least nine disorders, including DRPLA, HD, and Machado-Joseph disease. Initially, the discovery of neuronal intranuclear inclusions (NIIs) in human brains and in a murine model of HD provided a plausible hypothesis that the expression of expanded polyglutamine stretches leads to NII formation, resulting in neuronal cell death in selective brain regions characteristic to each disease. Recent studies, however, suggest that nuclear dysfunction, especially transcriptional abnormalities caused by the diffuse intranuclear accumulation of mutant proteins, plays a pivotal role in the development and progression of clinical symptoms. Polyglutamine diseases have a similarity with neuronal storage disease, and this pathological process might become a target for the establishment of an effective therapy for these diseases. [source] Reduced rates of axonal and dendritic growth in embryonic hippocampal neurones cultured from a mouse model of Sandhoff diseaseNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2003D. Pelled Sandhoff disease is a lysosomal storage disease in which ganglioside GM2 accumulates because of a defective ,-subunit of ,-hexosaminidase. This disease is characterized by neurological manifestations, although the pathogenic mechanisms leading from GM2 accumulation to neuropathology are largely unknown. We now examine the viability, development and rates of neurite growth of embryonic hippocampal neurones cultured from a mouse model of Sandhoff disease, the Hexb,/, mouse. GM2 was detected by metabolic labelling at low levels in wild type (Hexb+/+) neurones, and increased by approximately three-fold in Hexb,/, neurones. Hexb,/, hippocampal neurones were as viable as their wild type counterparts and, moreover, their developmental programme was unaltered because the formation of axons and of the minor processes which eventually become dendrites was similar in Hexb,/, and Hexb+/+ neurones. In contrast, once formed, a striking difference in the rate of axonal and minor process growth was observed, with changes becoming apparent after 3 days in culture and highly significant after 5 days in culture. Analysis of various parameters of axonal growth suggested that a key reason for the decreased rate of axonal growth was because of a decrease in the formation of collateral axonal branches, the major mechanism by which hippocampal axons elongate in culture. Thus, although the developmental programme with respect to axon and minor process formation and the viability of hippocampal neurones are unaltered, a significant decrease occurs in the rate of axonal and minor process growth in Hexb,/, neurones. These results appear to be in contrast to dorsal root ganglion neurones cultured from 1-month-old Sandhoff mice, in which cell survival is impaired but normal outgrowth of neurones occurs. The possible reasons for these differences are discussed. [source] Farber's disease diagnosed by nerve biopsyNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2002J. Jacobs Introduction:, Farber's disease (granulomatosis) is a rare inherited lipid storage disease caused by a deficiency of lysosomal acid-ceramidase. Clinical features include contractures of limbs with swelling of joints and multiple subcutaneous nodules. In a few cases there is prominent involvement of central and peripheral nervous systems. Ceramide accumulates in the nodules and in cells of many other tissues including brain. Electron microscopy of affected cells shows membrane-bound inclusions, some of which have a highly characteristic curved or ,banana' shape (Farber bodies). Nerve biopsy findings have been described in a few cases but our patient appears to be the first to have been diagnosed by nerve biopsy. Case report:, This male infant presented at 6 months with joint pain and swelling, fever weakness and nystagmus: EMNG demonstrated sensory-motor polyneuropathy with features of demyelination. Semi-thin resin sections show a moderately reduced density of myelinated fibres. The myelin sheaths of most fibres are inappropriately thin, which was confirmed morphometrically: some axons are demyelinated. Vacuolar inclusions are seen in some Schwann cells. Teased fibres show de- and remyelination. Electron microscopy shows oval, boomerang- or banana-shaped inclusions in Schwann cells associated with myelinated and unmyelinated axons, but not in other cell types. Conclusion:, Farber's disease is associated with a demyelinating neuropathy. [source] Early pulmonary involvement in Niemann-Pick type B disease: Lung lavage is not usefulPEDIATRIC PULMONOLOGY, Issue 2 2005Z.S. Uyan MD Abstract Niemann-Pick disease (NPD) is a rare, autosomal-recessively inherited lipid storage disease which is characterized by intracellular deposition of sphingomyelin in various body tissues. The disease is heterogeneous and classified into six groups. Pulmonary parenchymal involvement may be a feature of several subtypes of NPD, including type B. Progressive pulmonary involvement in NPD type B is a major cause of morbidity and mortality. It is usually diagnosed at older ages. Only a few cases with early pulmonary involvement have been reported. In this report, a patient with NPD type B, hospitalized with the diagnosis of pneumonia at age 3 months, is presented. Following treatment for pneumonia, she continued to have persistent respiratory symptoms and became oxygen-dependent. High-resolution computed tomography of the chest revealed diffuse interstitial changes. During follow-up, the patient developed hepatosplenomegaly. Lung, liver, and bone marrow biopsies showed characteristic findings for NPD. Biochemical studies also confirmed the diagnosis, and the sphingomyelinase enzyme level of the patient was low. Unilateral lung lavage was performed in order to decrease lipid storage as a treatment modality. However, there was no clinical or radiological improvement. The patient died at age 15 months due to progressive respiratory failure. Pulmonary involvement is a rare entity in early childhood in patients with NPD type B, but should be considered in the differential diagnosis of persistent interstitial lung disease. It may cause progressive respiratory failure, but the treatment options remain limited. Pediatr Pulmonol. 2005; 40:169,172. © 2005 Wiley-Liss, Inc. [source] Jordans' anomaly in a new neutral lipid storage diseaseAMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2009Elisa Piva No abstract is available for this article. [source] Prenatal diagnosis of free sialic acid storage disorders (SASD)PRENATAL DIAGNOSIS, Issue 8 2006Nina Aula Abstract Free sialic acid storage disorders, Salla disease (SD) and Infantile sialic acid storage disease (ISSD), are lysosomal storage diseases due to impaired function of a sialic acid transporter, sialin, at the lysosomal membrane. Several mutations of the sialin gene, SLC17A5, are known, leading either to the severe neonatal/infantile disease or to the milder, adult-type developmental disorder, Salla disease. Free sialic acid accumulation in lysosomes causes increased tissue concentration and consequently elevated urinary excretion. Prenatal diagnosis of SASD is possible either by determination of free sialic acid concentration or by mutation analysis of the SLC17A5 gene in fetal specimen, in chorionic villus biopsy particularly. Both techniques have been successfully applied in several cases, sialic acid assay more often in ISSD cases but mutation analysis preferentially in SD. Sialic acid assay of amniotic fluid supernatant or cultured amniotic fluid cells may give erroneous results and should not be used for prenatal diagnosis of these disorders. The present comments are mainly based on our experience of prenatal diagnosis of SD in Finnish families. A founder mutation in SLC17A5 gene, 115C-> T, represents 95% of the disease alleles in the Finnish SD patients, which provides a unique possibility to apply mutation analysis. Therefore, molecular studies have successfully been used in 17 families since the identification of the gene and the characterization of the SD mutations. Earlier, eight prenatal studies were performed by measuring the free sialic acid concentration in chorionic villus samples. Copyright © 2006 John Wiley & Sons, Ltd. [source] Hematologic iron analyte values as an indicator of hepatic hemosiderosis in callitrichidaeAMERICAN JOURNAL OF PRIMATOLOGY, Issue 7 2008Kristine M. Smith Abstract Hepatic hemosiderosis is one of the most common postmortem findings in captive callitrichid species. Noninvasive evaluation of hematologic iron analytes has been used to diagnose hepatic iron storage disease in humans, lemurs, and bats. This study evaluated the relationship between hematologic iron analyte values (iron, ferritin, total iron binding capacity, and percent transferrin saturation) and hepatic hemosiderosis in callitrichids at the Wildlife Conservation Society's Central Park and Bronx Zoos. Results revealed that both ferritin and percent transferrin saturation levels had strong positive correlations with hepatic iron concentration (P<0.001, r=0.77, n=20; P<0.001, r=0.85, n=10, respectively). Serum iron levels positively correlated with hepatic iron concentration (P=0.06, r=0.56, n=11), but this finding was not significant. Serum total iron binding capacity did not significantly correlate with hepatic iron concentration (P=0.47, r=0.25, n=10). Both ferritin and hepatic iron concentration positively correlated with severity of hepatic iron deposition on histology (P<0.05, r=0.49, n=21; P<0.001, r=0.67, n=21, respectively). This study suggests that ferritin, serum iron concentration, and percent transferrin saturation are convenient, noninvasive, antemortem methods for assessing severity of hemosiderosis in callitrichids. Am. J. Primatol. 70:629,633, 2008. © 2008 Wiley-Liss, Inc. [source] Restoration of central nervous system ,- N -acetylglucosaminidase activity and therapeutic benefits in mucopolysaccharidosis IIIB mice by a single intracisternal recombinant adeno-associated viral type 2 vector deliveryTHE JOURNAL OF GENE MEDICINE, Issue 7 2010Haiyan Fu Abstract Background Finding efficient central nervous system (CNS) delivery approaches has been the major challenge facing therapeutic development for treating diseases with global neurological manifestation, such as mucopolysaccharidosis (MPS) IIIB, a lysosomal storage disease, caused by autosomal recessive defect of ,- N -acetylglucosaminidase (NaGlu). Previously, we developed an approach, intracisternal (i.c.) injection, to deliver recombinant adeno-associated viral (rAAV) vector to the CNS of mice, leading to a widespread periventricular distribution of transduction. Methods In the present study, we delivered rAAV2 vector expressing human NaGlu into the CNS of MPS IIIB mice by an i.c. injection approach, to test its therapeutic efficacy and feasibility for treating the neurological manifestation of the disease. Results We demonstrated significant functional neurological benefits of a single i.c. vector infusion in adult MPS IIIB mice. The treatment slowed the disease progression by mediating widespread recombinant NaGlu expression in the CNS, resulting in the reduction of brain lysosomal storage pathology, significantly improved cognitive function and prolonged survival. However, persisting motor function deficits suggested that pathology in areas outside the CNS contributes to the MPS IIIB behavioral phenotype. The therapeutic benefit of i.c. rAAV2 delivery was dose-dependent and could be attribute solely to the CNS transduction because the procedure did not lead to detectable transduction in somatic tissues. Conclusions A single IC rAAV2 gene delivery is functionally beneficial for treating the CNS disease of MPS IIIB in mice. It is immediately clinically translatable, with the potential of improving the quality of life for patients with MPS IIIB. Copyright © 2010 John Wiley & Sons, Ltd. [source] Normoglycaemia in Type 1b glycogen storage disease with difficult venous accessANAESTHESIA, Issue 10 2009S. Hammond No abstract is available for this article. [source] Exclusion of NEU1 and PPGB from candidate genes for a lysosomal storage disease in Japanese Black cattleANIMAL SCIENCE JOURNAL, Issue 5 2009Ali Akbar MASOUDI ABSTRACT A case of lysosomal storage disease has been reported in a calf of Japanese Black cattle. Lysosomal storage diseases are hereditary diseases caused by deficiency of lysosomal hydrolases. The clinical and pathological features and accumulated substrates of the affected animal indicated a possibility of sialidosis or galactosialidosis caused by deficiency of neuraminidase (NEU1) or protective protein for ,-galactosidase (PPGB). In the present study, we investigated nucleotide sequences of the genes encoding these two proteins to evaluate whether mutation of these genes is involved in this disease. We determined cattle genomic sequences of these two genes by using bovine EST sequences and the nucleotide sequences of all exons of these genes were compared between affected and normal animals. The results showed several nucleotide substitutions, but none of them was a functional mutation or specific to the affected animal. Furthermore, genotyping of the microsatellite markers in the vicinity of these two genes revealed no homozygosity of the chromosomal regions including these genes in the affected animal. These findings indicated that neither NEU1 nor PPGB gene is responsible for the lysosomal storage disease of Japanese Black cattle and therefore the disease is neither sialidosis nor galactosialidosis. [source] Fungal community diversity and soil health in intensive potato cropping systems of the east Po valley, northern ItalyANNALS OF APPLIED BIOLOGY, Issue 2 2009L.M. Manici Abstract An ecological approach was used to investigate the relationship between diversity of soil fungal communities and soil-borne pathogen inoculum in a potato growing area of northern Italy affected by yield decline. The study was performed in 14 sites with the same tillage management practices: 10 named ,potato sites', that for many years had been intensely cultivated with potatoes, and 4 named ,rotation sites', subject to a 4-year rotation without potatoes or any recurrent crop for many years. Fungal communities were recorded using conventional (soil fungi by plate count and endophytic fungi as infection frequency on pot-grown potato plant roots in soil samples) and molecular approaches [Basidiomycetes and Ascomycetes with specific and denaturing gradient gel electrophoresis (DGGE) analysis]. Diversity of fungal communities in potato sites was significantly lower than that in rotation sites. In addition, fungal communities in rotation sites showed lower Berger,Parker dominance than those in the potato sites, suggesting that rotation sites had a higher diversity as well as a better fungal community balance than potato sites. The ANalysis Of SIMilarity test of soil fungi and root endophytic fungi revealed that the two cropping systems differed significantly for species composition. Root endophytic fungal communities showed a greater ability to colonise potato roots in soil samples from potato sites than those from rotation sites. Moreover, the majority of endophytic root fungal community species in potato sites belonged to the potato root rot complex and storage disease (Colletotrichum coccodes, Fusarium solani and Fusarium oxysporum), while those in rotation sites were mainly ubiquitous or saprobic fungi. Soil rDNA analyses showed that Ascomycetes were much more frequent than Basidiomycetes in all the soils examined. DGGE analysis, with the Ascomycete-specific primer (ITS1F/ITS4A), did not reveal distinctions between the communities found at the potato and rotation sites, although the same analysis showed differences between the communities of Basidiomycetes (specific primer ITS1F/ITS4B). These findings showed that recurrent potato cropping affected diversity and composition of soil fungal communities and induced a shift in specialisation of the endophytic fungi towards potato. [source] Free sialic acid storage disease without sialuria,ANNALS OF NEUROLOGY, Issue 6 2009Fanny Mochel MD We performed high-resolution in vitro proton nuclear magnetic resonance spectroscopy on cerebrospinal fluid and urine samples of 44 patients with leukodystrophies of unknown cause. Free sialic acid concentration was increased in cerebrospinal fluid of two siblings with mental retardation and mild hypomyelination. By contrast, urinary excretion of free sialic acid in urine was normal on repeated testing by two independent methods. Both patients were homozygous for the K136E mutation in SLC17A5, the gene responsible for the free sialic acid storage diseases. Our findings demonstrate that mutations in the SLC17A5 gene have to be considered in patients with hypomyelination, even in the absence of sialuria. Ann Neurol 2009;65:753,757 [source] Avascular necrosis of the femoral head in a patient with Fabry's disease: Identification of ceramide trihexoside in the bone by delayed-extraction matrix-assisted laser desorption ionization,time-of-flight mass spectrometryARTHRITIS & RHEUMATISM, Issue 7 2002Hiroshi Horiuchi Fabry's disease is a lipid storage disease caused by an X-linked hereditary deficiency of ,-galactosidase. The enzymatic defect causes progressive deposition of ceramide trihexoside (CTH) in various tissues, leading to renal failure, premature myocardial infarction, and stroke, with a high rate of mortality in younger patients. Among the complications associated with Fabry's disease, a few cases involving avascular necrosis (AVN) of the femoral head have been reported. However, direct evidence of deposition of CTH in bone marrow in the femoral head has not been demonstrated. This report describes a 58-year-old man who underwent total hip arthroplasty for femoral head AVN associated with Fabry's disease. The accumulation of CTH was examined by chemical analysis of the sphingolipid extracted from the femoral head, using delayed-extraction matrix-assisted laser desorption ionization,time-of-flight mass spectrometry. This is the first report confirming the presence of CTH in the sphingolipid fraction from normal and necrotic bone of a patient with Fabry's disease. [source] A case of multiple angiomas without any angiokeratomas in a female heterozygote with Fabry diseaseAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 1 2010Vesna Mirceva ABSTRACT Fabry disease is a rare, X-chromosome-linked lysosomal storage disease caused by a deficient ,-galactosidase A enzyme. The disease manifests primarily in affected hemizygous males and to some extent in heterozygous females (,carrier'). A 45-year-old female Fabry disease patient without angiokeratomas but with numerous angiomas is presented. Her leukocyte ,-galactosidase A activity was reduced (0.35 nmol/min/mg protein; normal range: 0.4,1). The analysis of her ,-galactosidase A gene (exon 1,7) showed the transition c.427 G>A. An intrafamilial follow-up search detected a reduced leukocyte ,-galactosidase A activity in her father, who suffered exclusively from coronary heart disease. Our case report underlines the possible wide range of clinical signs in Fabry disease patients, sometimes complicated by missing typical lesions (e.g. angiokeratomas). In oligosymptomatic Fabry disease cases, genetic analysis is recommended. [source] Is there a role for dynamic retinal vessel analysis in internal medicine?ACTA OPHTHALMOLOGICA, Issue 2008IM LANZL Purpose Human retinal vessels and their reaction to stimuli change during life and in disease due to physiological, genetic and pathological influences. Using the Dynamic Vessel Analyzer (DVA, Fa. IMEDOS, Jena) it is possible to assess changes in retinal vessel diameters in response to vasoactive stimuli in real time and non-invasively. Methods Retinal arterial vessel reaction in the natural time course and to the average of 3 consecutive monochromatic flicker stimulations (530-600 nm, 12,5 Hz, 20 s) with a 80 s observation pause between stimulations was investigated in healthy volunteers of different age groups, obese patients, diabetes type 1 patients, systemic hypertensive patients and patients with lysosomal storage disease. Statistical data analysis of vessel reactions independent from the DVA program was performed. Results There is a statistically significant difference in retinal vascular behaviour in different age groups in a healthy population. The same is true between a healthy population and each of the diseases investigated. Lysosomal storage disease however demonstrated an increase in dilation following flicker stimulation compared to normal persons. Conclusion Flicker stimulation of the retina light evokes a prompt vessel reaction in all healthy subjects. We could demonstrate an age dependence of the retinal arterial reaction in medically healthy persons and in hypertension, diabetes and obese patients. From the increased reaction in lysosomal storage disease further understanding of different factors leading to the vascular reaction to stimuli may be derived. Application of flicker stimulus to retinal vessels represents a method to assess the endothelial function of vessels which is important to understand in systemic disease. [source] Fetal hydrops in GM1 gangliosidosis: A case reportACTA PAEDIATRICA, Issue 12 2005Maria Teresa Sinelli Abstract GM1 gangliosidosis is a rare disorder characterized by deficiency of the ,-galactosidase enzyme, with the resulting accumulation of glycolipids, oligosaccharides and especially GM1 ganglioside. It can be classified into three clinical types according to the time of onset: infantile, juvenile and adult form. We report a case of GM1 gangliosidosis presenting with fetal hydrops at 24 wk of gestation. The parents were consanguineous; the baby, born at 35 wk of gestation, was dysmorphic and presented severe generalized oedema. The most common cause of fetal hydrops was excluded. A lysosomal storage disease was suspected, and GM1 gangliosidosis was diagnosed. The child developed severe growth and mental retardation and died when she was 21 mo old. Conclusion: We suggest that the possible association between inborn errors of metabolism and antenatal ascites should be considered, in order to offer genetic counselling due to the high recurrence risk and the availability of early antenatal diagnosis. [source] Treatment of neutral glycosphingolipid lysosomal storage diseases via inhibition of the ABC drug transporter, MDR1FEBS JOURNAL, Issue 9 2006Cyclosporin A can lower serum, liver globotriaosyl ceramide levels in the Fabry mouse model We have shown that the ABC transporter, multiple drug resistance protein 1 (MDR1, P-glycoprotein) translocates glucosyl ceramide from the cytosolic to the luminal Golgi surface for neutral, but not acidic, glycosphingolipid (GSL) synthesis. Here we show that the MDR1 inhibitor, cyclosporin A (CsA) can deplete Gaucher lymphoid cell lines of accumulated glucosyl ceramide and Fabry cell lines of globotriaosyl ceramide (Gb3), by preventing de novo synthesis. In the Fabry mouse model, Gb3 is increased in the heart, liver, spleen, brain and kidney. The lack of renal glomerular Gb3 is retained, but the number of verotoxin 1 (VT1)-staining renal tubules, and VT1 tubular targeting in vivo, is markedly increased in Fabry mice. Adult Fabry mice were treated with ,-galactosidase (enzyme-replacement therapy, ERT) to eliminate serum Gb3 and lower Gb3 levels in some tissues. Serum Gb3 was monitored using a VT1 ELISA during a post-ERT recovery phase ± biweekly intra peritoneal CsA. After 9 weeks, tissue Gb3 content and localization were determined using VT1/TLC overlay and histochemistry. Serum Gb3 recovered to lower levels after CsA treatment. Gb3 was undetected in wild-type liver, and the levels of Gb3 (but not gangliosides) in Fabry mouse liver were significantly depleted by CsA treatment. VT1 liver histochemistry showed Gb3 accumulated in Kupffer cells, endothelial cell subsets within the central and portal vein and within the portal triad. Hepatic venule endothelial and Kupffer cell VT1 staining was considerably reduced by in vivo CsA treatment. We conclude that MDR1 inhibition warrants consideration as a novel adjunct treatment for neutral GSL storage diseases. [source] Genetic background of Japanese patients with adult-onset storage diseases in the liverHEPATOLOGY RESEARCH, Issue 10 2007Hisao Hayashi In contrast to primary lysosomal diseases in young subjects, adult-onset liver storage disorders may be explained by non-lysosomal genetic defects. The aim of the present review is to summarize the genetic backgrounds of Japanese patients with hemochromatosis of unknown etiology, Wilson disease of primary copper toxicosis, and the black liver of Dubin,Johnson syndrome. Three patients with middle-age onset hemochromatosis were homozygous for mutations of HJV and two patients were homozygous for mutations of TFR2. Minor genes other than HJV and TFR2 might be involved in Japanese patients. Five of the six patients with Wilson disease were compound heterozygous, while the remaining patient was heterozygous for the mutation in ATP7B responsible for copper toxicosis. Involvement of MURR1 was not proved in the heterozygote of ATP7B. Because of ferroxidase deficiency,most patients had secondary lysosomes shared by cuprothioneins and iron complex. Six patients with Dubin,Johnson syndrome were homozygous or compound heterozygous for mutant MRP2. Despite complex metabolic disorders, the syndrome had a single genetic background. Thus, most patients with adult-onset lysosomal proliferation in the liver had genetic defects in non-lysosomal organelles, named the secondary lysosomal diseases. The proliferating lysosomes in these conditions seemed to be heterogeneous in their matrices. [source] Defective calcium homeostasis in the cerebellum in a mouse model of Niemann,Pick A diseaseJOURNAL OF NEUROCHEMISTRY, Issue 6 2005Luba Ginzburg Abstract We recently demonstrated that calcium homeostasis is altered in mouse models of two sphingolipid storage diseases, Gaucher and Sandhoff diseases, owing to modulation of the activities of a calcium-release channel (the ryanodine receptor) and of the sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA) respectively, by the accumulating sphingolipids. We now demonstrate that calcium homeostasis is also altered in a mouse model of Niemann,Pick A disease, the acid sphingomyelinase (A-SMase)-deficient mouse (ASM,/,), with reduced rates of calcium uptake via SERCA in the cerebellum of 6,7-month-old mice. However, the mechanism responsible for defective calcium homeostasis is completely different from that observed in the other two disease models. Thus, levels of SERCA expression are significantly reduced in the ASM,/, cerebellum by 6,7 months of age, immediately before death of the mice, as are levels of the inositol 1,4,5-triphosphate receptor (IP3R), the major calcium-release channel in the cerebellum. Systematic analyses of the time course of loss of SERCA and IP3R expression revealed that loss of the IP3R preceeded that of SERCA, with essentially no IP3R remaining by 4 months of age, whereas SERCA was still present even after 6 months. Expression of zebrin II (aldolase C), a protein found in about half of the Purkinje cells in the adult mouse cerebellum, was essentially unchanged during development. We discuss possible pathological mechanisms related to calcium dysfunction that may cause Purkinje cell degeneration, and as a result, the onset of neuropathology in Niemann,Pick A disease. [source] | ||||||||||||||||||||||||||||||||||