Types Of MPS Research Articles

AB084. Cause of death and clinical characteristics of 34 mortality patients with mucopolysaccharidosis II in Taiwan, 1995-2012.

Background and objective Mucopolysaccharidosis type II (MPS II; Hunter syndrome; OMIM +309900) is an X-linked recessive, multisystemic lysosomal storage disorder caused by iduronate-2-sulfatase (I2S) deficiency, which catalyzes a step in the catabolism of glycosaminoglycans (GAGs). It leads to accumulation of GAGs in the lysosomes of many organs and tissues, causing progressive cellular dysfunction. MPS II has a variable age of onset and variable rate of progression. In Asian countries, there is a relatively higher incidence of MPS II compared to other types of MPS. The study aims to delineate the cause of death and natural history of Taiwanese patients with MPS II.

АВТОМАТИЗОВАНА КЛІНІЧНА БАЗА МОНІТОРИНГУ ХВОРИХ НА МУКОПОЛІСАХАРИДОЗ

This article describes the complexity of managing medical records of patients with MPS and monitoring them throughout their live. A general solution of these problems is produced by implementing an automated clinical database for monitoring the patients with mucopolysacharidosis. This application is designed to record and store information about patients with six types of MPS . The user can create, edit, store patient records , which include such data as the patients passport information, visits, test results, method of treatment , objective status . Also, the application has such functions such as : patient data search using a variety of filters, tracking patients visits on current week, estimation of the total requirement of drugs and the cost of these drugs.

Urine keratan sulfate (uKS) elevation in lysosomal disorders (LSD): Comparison of uKS levels in Morquio/MPS IV versus non-Morquio LSD

CO RR EC TE D P RO OF patients affected with different types of MPS, such as Hurler, Hurler/ Scheie and Scheie (MPS I/H, IH/S, I/S), Hunter (MPS II), Sanfilippo (MPS III), Morquio (MPS IV) and Maroteaux–Lamy (MPS VI) syndromes. Therefore, we have developed a quantitative methodology for the analysis of urine samples using an ultra-performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) multiplex approach. Specific glycosaminoglycans such as dermatan sulfate (DS), heparan sulfate (HS), and keratan sulfate (KS) were specifically targeted for mass spectrometry analysis. Twenty-five microliters of urine was evaporated at room temperature under a nitrogen flow. A methanolysis reaction was performed by adding methanol–HCl·3N to the dried urine sample, followed by heating at 65 °C for 60 min. After a second nitrogen evaporation, the residue was suspended in 200 μl of a solution containing deuterated internal standards synthesized in-house. Two microliters were injected onto an Acquity I-Class UPLC coupled to a Xevo TQ-S mass spectrometry system (Waters Corp.). The high sensitivity and good resolution of this methodology allowed the detection of small quantities of urinary GAG. Urinary excretion of specific GAG permitted a good differentiation between patients with MPS I, II, III, IV and VI and healthy reference controls. Except for MPS I and II which are characterized by the same GAG excretion profile, each MPS type was distinguished from one another due to a specific GAG profile. This UPLC–MS/MS quantitation of dermatan sulfate, heparan sulfate, and keratan sulfate is specific and sensitive for the detection of MPS disorders. This methodology might be applicable to high-risk screening and reliable for the diagnosis, and monitoring of treated MPS patients.

The Effect of Multiple Sulfatase Deficiency (MSD) on Dental Development: Can We Use the Teeth as an Early Diagnostic Tool?

Multiple sulfatase deficiency (MSD) is a rare autosomal recessive inborn error of metabolism due to reduced catalytic activity of the different sulfatase. Affected individuals show neurologic deterioration with mental retardation, skeletal anomalies, organomegaly, and skin changes as in X-linked ichthyosis. The only organ that was not examined in MSD patients is the dentition. To evaluate the effect of the metabolic error on dental development in a patient with the intermediate severe late-infantile form of MSD (S155P). Histological and chemical study were performed on three deciduous and five permanent teeth from MSD patient and pair-matched normal patients. Tooth germ size and enamel thickness were reduced in both deciduous and permanent MSD teeth, and the scalloping feature of the DEJ was missing in MSD teeth causing enamel to break off from the dentin. The mineral components in the enamel and dentin were different. The metabolic error insults the teeth in the stage of organogenesis in both the deciduous and permanent dentition. The end result is teeth with very sharp cusp tips, thin hypomineralized enamel, and exposed dentin due to the break off of enamel. These findings are different from all other types of MPS syndromes.Clinically the phenotype of intermediate severe late-infantile form of MSD appeared during the third year of life. In children of parents that are carriers, we can diagnose the disease as early as birth using X-ray radiograph of the anterior upper region or as early as 6-8 months when the first deciduous tooth erupt and consider very early treatment to ameliorate the symptoms.

Clinical Significance Of Circulating Microparticles In Ph- Myeloproliferative Neoplasms (MPN)

BackgroundMicroparticles (MPs) are small membrane vesicles that are classified as red blood cell MPs (RMPs), platelet-derived MPs (PMPs), tissue factor MPs (TF+MPs) and endothelial MPs (EMPs) based on their origins. Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPN) are disorders characterized by abnormal hematopoiesis, thrombosis, JAK2V617F mutation. Although MPs are considered as biomarkers reflecting procoagulant state in cancer patients, their involvement in the patients with Ph-MPN remains unclear. Our objective in this study was to measure the alterations of the four MPs types in the patients with MPN and to evaluate their correlations with JAK2V617F mutation and some clinical complications, especially for thrombosis and splenomegaly. MethodsSixty-seven patients with MPN were enrolled in this study, including 12 polycythaemia vera (PV), 49 essential thrombocythemia (ET) and 6 primary myelofibrosis (PMF). 30 healthy donors were selected as normal controls. Venous blood was anticoagulated with sodium citrate (1:9). Using flow cytometry, plasma samples were measured for RMPs, PMPs, TF+MPs and EMPs with phycoerythrin (PE)-conjugated monoclonal antibodies CD235a, CD61, CD142, and CD62E, respectively. Forward scatter was set in scale using fluorescent microspheres of 0.8μm and standard fluorescent microbeads (0-0.8μm) in diameter were used to set the microparticle gate. Data were expressed as median (M) and interquartile range (IQR). Meanwhile, genomic DNA was extracted from mononuclear cells and amplified by allele specific polymerase chain reaction (PCR). Results(1) Patients with MPN showed significantly higher plasma levels for all four MPs compared with healthy donors (P<0.05), namely 49.0/μl (15.8-109.5/μl) vs 21.0/μl (13.8-32.6/μl) for RMPs, 181.2/μl(75.8-1111.6/μl) vs 74.9/μl (55.5-115.4/μl) for PMPs, 48.1/μl (13.1-72.4/μl) vs 31.0/μl (14.9-47.6/μl) for TF+MPs and 310.2/μl (128.6-1130.5/μl) vs 155.9/μl (100.3-227.6/μl) for EMPs. (2) Among different subtypes of MPN, PMPs were higher in patients with PMF than patients with PV and ET (P<0.05), but there was no significant difference between PV and ET group. No obvious difference was found in RMPs, TF+MPs and EMPs among different subtypes of MPN patients. (3) MPN patients with JAK2V617F mutation (n=34) were found to have higher plasma levels of TF+MPs and RMPs than those without mutation (P<0.05) and this difference was not found for PMPs and EMPs. (4) MPN patients with various thrombotic complications (n=10) showed higher levels of all four types of MPs than those without thrombotic complications (n=31) (P<0.05). Elevated MP levels were also found in patients with splenomegaly (n=19) compared to those without splenomegaly (n=14) (P<0.05). ConclusionHigher levels of MPs were observed in MPN patients compared with healthy controls, especially in patients complicated with thrombosis and splenomegaly, which reflects a prothrombotic state. Moreover, significantly increased TF+MPs and RMPs were found in MPN patients with JAK2V617F mutatioin. Disclosures:No relevant conflicts of interest to declare.

Enhancement of Cost-effectiveness and Activity of Formaldehyde Dehydrogenase by Immobilization onto Mesoporous Silica with an Interparticle Pore Structure

Abstract Mesoporous silica (MPS) materials with cylindrical pore and interparticle mesoporous silica (IPMPS) were synthesized by common sol–gel methods. Using these two types of MPS, we examined the effect of enzyme activity on MPS with different pore structures. We observed that enzymes immobilized on IPMPS showed a higher activity.

Levels of Circulating Microparticles in Lung Cancer Patients and Possible Prognostic Value

Background. Endothelial-derived microparticles (EDMPs) and platelet-derived microparticles (PDMPs) have been reported to be increasing in various diseases including malignant diseases. Here, we investigated whether these MPs may be useful biomarkers for predicting lung cancer (LC) disease status, cell type, or metastasis. Methods and Results. One hundred and thirty LC patients were prospectively enrolled into the study between April 2011 and February 2012. Flow cytometric analysis demonstrated that the circulating levels of platelet-derived activated MPs (PDAc-MPs), platelet-derived apoptotic MPs (PDAp-MPs), endothelial-derived activated MPs (EDAc-MPs), and endothelial-derived apoptotic MPs (EDAp-MPs) were significantly higher in LC patients than in 30 age- and gender-matched normal control subjects (all P < 0.05). Additionally, circulating level of PDAc-MPs was significantly lower (P = 0.031), whereas the circulating levels of the other three biomarkers did not differ (all P > 0.1) in early stage versus late stage LC patients. Furthermore, the circulating levels of the four types of MPs did not differ among patients with different disease statuses (i.e., disease controlled, disease progression, and disease without treatment, i.e., fresh case) (all P > 0.2) or between patients with or without LC metastasis (all P > 0.5). Moreover, only the circulating level of EDAp-MPs was significantly associated with the different cell types (i.e., squamous cell carcinoma, adenocarcinoma, and small cell carcinoma) of LC (P = 0.045). Conclusion. Circulating MP levels are significantly increased in LC patients as compared with normal subjects. Among the MPs, only an increased level of EDAp-MPs was significantly associated with different LC cell types.

Behavioral consequences of mixed electoral systems: Deviating voting behavior of district and list MPs in the German Bundestag

Electoral rules should affect parliamentary behavior. In particular, deputies elected from single-member districts should be more likely to deviate from the party line than deputies elected under proportional representation. This paper suggests a framework for conceptualizing and modeling the effect of the type of mandate on deputies’ propensity to cast deviating votes in mixed electoral systems. The proposed modeling strategy uses disaggregated voting data and integrates dependencies among observations in a multi-level design. Empirically, the paper analyses voting behavior in the 16th German Bundestag (2005–2009) and shows that the odds of district MPs to deviate are significantly higher despite frequent claims that the two types of MPs behave alike. However, the behavioral differences cannot be attributed to attempts by district MPs to follow their local constituents as competing principals.

Validation of keratan sulfate level in mucopolysaccharidosis type IVA by liquid chromatography–tandem mass spectrometry

Mucopolysaccharidosis type IVA (MPS IVA, Morquio A disease), a progressive lysosomal storage disease, causes skeletal chondrodysplasia through excessive storage of keratan sulfate (KS). KS is synthesized mainly in cartilage and released to the circulation. The excess storage of KS disrupts cartilage, consequently releasing more KS into circulation, which is a critical biomarker for MPS IVA. Thus, assessment of KS level provides a potential screening strategy and determines clinical course and efficacy of therapies. We have recently developed a tandem mass spectrometry liquid chromatography [LC/MS/MS] method to assay KS levels in blood. Forty-nine blood specimens from patients with MPS IVA [severe (n = 33), attenuated (n = 11) and undefined (n = 5)] were analyzed for comparison of blood KS concentration with that of healthy subjects and for correlation with clinical severity. Plasma samples were digested by keratanase II to obtain disaccharides of KS. Digested samples were assayed by LC/MS/MS. We found that blood KS levels (0.4-26 µg/ml) in MPS IVA patients were significantly higher than those in age-matched controls (0.67-4.6 µg/ml; P < 0.0001). It was found that blood KS level varied with age and clinical severity in the patients. Blood KS levels in MPS IVA peaked between 2 years and 5 years of age (mean 11.4 µg/ml). Blood KS levels in severe MPS IVA (mean 7.3 µg/ml) were higher than in the attenuated form (mean 2.1 µg/ml) (P = 0.012). We also found elevated blood KS levels in other types of MPS. These findings indicate that the new KS assay for blood is suitable for early diagnosis and longitudinal assessment of disease severity in MPS IVA.

Enzyme-functionalized mesoporous silica for bioanalytical applications

The unique properties of mesoporous silica materials (MPs) have attracted substantial interest for use as enzyme-immobilization matrices. These features include high surface area, chemical, thermal, and mechanical stability, highly uniform pore distribution and tunable pore size, high adsorption capacity, and an ordered porous network for free diffusion of substrates and reaction products. Research demonstrated that enzymes encapsulated or entrapped in MPs retain their biocatalytic activity and are more stable than enzymes in solution. This review discusses recent advances in the study and use of mesoporous silica for enzyme immobilization and application in biosensor technology. Different types of MPs, their morphological and structural characteristics, and strategies used for their functionalization with enzymes are discussed. Finally, prospective and potential benefits of these materials for bioanalytical applications and biosensor technology are also presented.

Proteomic discovery of 21 proteins expressed in human plasma-derived but not platelet-derived microparticles

Microparticles (MPs) are small membrane vesicles generated by essentially all cell types. In the plasma, most MPs are derived from platelets, but those from other sources, particularly leukocytes (macrophages, lymphocytes, and neutrophils), endothelial cells, and even smooth muscle cells can be detected and appear to play an important role in normal physiology and various diseases. In previous work we analyzed the proteome of MPs generated from isolated platelets (platelet MPs). Here, we report on a comparative analysis of microparticles isolated from plasma (plasma MPs) versus platelet MP using two complementary methods of comparative analysis. The first method, spectral count analysis, yielded 21 proteins detected in plasma MPs (with a total spectral count of 10 or greater) that were essentially absent in platelet MPs (with a total spectral count of 1 or 0). An additional two proteins (von Willebrand Factor, albumin) were present in both types of MPs but enriched in the plasma MPs. The second method, isotope-coded affinity tag (ICAT) labeling of proteins, supported the spectral count results for the more abundant proteins and provided better relative quantitation of differentially expressed proteins. Proteins present only in the plasma MPs include several associated with apoptosis (CD5-like antigen, galectin 3 binding protein, several complement components), iron transport (transferrin, transferrin receptor, haptoglobin), immune response (complement components, immunoglobulin J and kappa chains), and the coagulation process (protein S, coagulation factor VIII).

Color and COD retention by nanofiltration membranes

In the present study the application of the nanofiltration process was investigated mainly in the retention ofcolor and chemical oxygen demand (COD) present in textile industry wastewater. Nanofiltration experiments were carried out in a pilot unit, operating in crossflow. Three different types of spiral wound membranes, DK 1073, NF 45 and MPS 31 were used simultaneously in the same unit. The results of the tests showed that for color retention, the values were around 99% for the DK 1073 and NF 45 membranes and the 87% for COD retention for the DK 1073. The permeate flux for the different wastewaters varied from 30.5 to 70 L/h.m 2. Fouling was observed in all membranes due to the accumulation of molecular species close to the filtering surface. The process was efficient and promising for the reuse of wastewater from this type of industry.

Peasants' Uprising or Religious War? Re-examining the 1975 Conservative Leadership Contest

This article analyses the nature of the support given to the candidates in the 1975 Conservative leadership contest, in which Margaret Thatcher replaced Edward Heath. In contrast to the orthodox account of the contest – which interprets it as largely non-ideological – the article argues that there were clear ideological forces at work. The right strongly supported Thatcher in both rounds; the left strongly backed Heath and then Whitelaw. Region, experience and education also influenced the voting. The traditional accounts, which explain those voting for Thatcher as doing so simply because she was not Heath, have, therefore, to explain why only certain types of MPs felt this way. Margaret Thatcher may have won because she was not Ted Heath; but she did not win solely because she was not Ted Heath.

The Influence of the Ethnic Composition of Australian Federal Electorates on the Parliamentary Responsiveness of MPs to their Ethnic Sub-constituencies

This paper examines the parliamentary responsiveness of Australian MPs with respect to their ethnic constituents in the official arena of representation, the federal parliament. It first reviews the notion of representation and discusses the twofold influence that ethnicity may exert on the representational behaviour of elected representatives: the ethnicity of the electorate and the ethnicity of the elected representative. It then presents and discusses the results of a content analysis of the parliamentary interventions of MPs from 12 ethnic electorates and 10 non-ethnic electorates between 1983 and 1996. On the basis of this analysis, two indexes were constructed, the ethnic reference ratio and the ethnic distance ratio in order to compare the responsiveness of MPs to their ethnic constituents. The findings suggest that the ethnicity of the electorate does have an influence on ethnic responsiveness in absolute terms but less so in relative terms. In other words, MPs from ethnic electorates generally make more ethnic-related interventions than MPs from non-ethnic electorates, but not as much as the proportion of ethnic constituents in these electorates would suggest they should make. The ethnicity of the electorate also influences the types of ethnic issues MPs make, with those from ethnic seats more likely to make constituency-related issues. The marginality of the seat, especially in ethnic electorates, rather than the political party to which the representative belongs, would appear to have a bigger influence on the degree and type of responsiveness. Finally, the ethnicity of the MP does have an influence in both the degree and type of ethnic responsiveness.