Existence Of Antibodies Research Articles

Zwitterionic polymer with minimal reactivity against PEG antibodies to enhance the therapeutic effects of cytokine-targeting DNA aptamer.

Overcoming poor in vivo pharmacokinetics is a critical challenge in developing therapeutic aptamers, and conjugation to poly(ethylene glycol) (PEG) is a well-established technique for aptamers to prolong blood circulation. However, the existence of antibodies that specifically recognize PEG and their adverse effects on in vivo behaviors have been increasingly reported, highlighting the necessity of alternative modification strategies for aptamers. To address this issue, we focused on a zwitterionic polymer, particularly poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), as a PEG alternative to modify DNA aptamers. We conjugated PMPC to a DNA aptamer targeting IFN-gamma and investigated the properties of the PMPC-conjugated DNA aptamer as a therapeutic agent. PMPC modification did not affect the neutralizing activity of the aptamer. PMPC demonstrated lower reactivity against anti-PEG antibodies than PEG-like aptamer modifiers previously reported to exhibit low reactivity against PEG antibodies. In addition, PMPC extended the blood circulation time of the aptamer as long as or longer than PEG with a similar molecular size. In the LPS-induced inflammation animal model, the survival rate after treatment with the PMPC-aptamer conjugate was significantly superior to that with unmodified aptamer. These results indicate that PMPC has potential as an aptamer or other nucleic acid drug modifier to replace or be compatible with PEG.

Seroprevalence and associated risk factors for Fasciola hepatica in sheep in Nile Delta of Egypt

Fascioliasis is a globally distributed zoonotic parasitic disease that affects ruminants, including sheep. This study conducted from January to December 2023, aimed to determine the prevalence of Fasciola hepatica in sheep across three governorates in Egypt's Nile Delta and to assess associated risk factors. A total of 455 serum samples were analyzed using a commercial ELISA kit, revealing antibodies against F. hepatica in 22.2 % of the tested sheep. There was no significant association between locality or sex and the seroprevalence of F. hepatica in sheep; however, the highest prevalence was observed in Kafr ElSheikh and in female sheep.Concerning risk factors, poor conditioned sheep aged between 1 and 2 years showed 2.1 and 3.8 times higher of infection probability than others. In addition, the risk of F. hepatica infection in sheep increased significantly in winter season (OR = 6.6, 95 %CI: 2.6–16.8), in absence of prophylactic treatment (OR = 2.2, 95 %CI: 1.3–3.3) and in presence of snail (OR = 3, 95 %CI: 3–5.4). The existence of antibodies against F. hepatica in examined sheep raising in Nile Delta indicating that the disease is reported in the studied areas and needs to be managed on farms through control and preventative measures.

Anti-NMDAR antibodies, the blood-brain barrier, and anti-NMDAR encephalitis.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an antibody-related autoimmune encephalitis. It is characterized by the existence of antibodies against NMDAR, mainly against the GluN1 subunit, in cerebrospinal fluid (CSF). Recent research suggests that anti-NMDAR antibodies may reduce NMDAR levels in this disorder, compromising synaptic activity in the hippocampus. Although anti-NMDAR antibodies are used as diagnostic indicators, the origin of antibodies in the central nervous system (CNS) is unclear. The blood-brain barrier (BBB), which separates the brain from the peripheral circulatory system, is crucial for antibodies and immune cells to enter or exit the CNS. The findings of cytokines in this disorder support the involvement of the BBB. Here, we aim to review the function of NMDARs and the relationship between anti-NMDAR antibodies and anti-NMDAR encephalitis. We summarize the present knowledge of the composition of the BBB, especially by emphasizing the role of BBB components. Finally, we further provide a discussion on the impact of BBB dysfunction in anti-NMDAR encephalitis.

Seroprevalence and Risk Factors of Infectious Bovine Rhinotracheitis in Dairy Cattle of Chitwan, Nawalpur and Rupandehi Districts of Nepal

The cross-sectional study from July 2018 to September 2018 was conducted to determine the seroprevalence and risk factors of Infectious Bovine Rhinotracheitis (IBR) in cattle of the Chitwan, Nawalpur, and Rupandehi districts of Nepal. The existence of antibodies against IBR was investigated in 92 serum samples obtained systematically from 55 cattle herds using Indirect-ELISA. A questionnaire interview was done to collect individual and herd-level data. The association between categorical variables and the outcome variable (seropositive) was assessed by bivariate analysis and multivariate logistic regression analysis in SPSS version 19.0. The seroprevalence of IBR was 18.48% (95% CI: 11.1-27.9), and district, breed, and herd size were identified as potential risk factors for IBR seropositivity. Significantly higher risk for IBR was found in Chitwan (Percentage-Positive “PP” = 36.37%; Odd ratio “OR” = 5.211; p = 0.008) than in Nawalpur (PP = 9.38%; OR = 0.931) and Rupandehi (PP = 10.00%). PP of IBR was significantly higher in Jersey crosses (PP = 30.00%; OR = 2.893; p = 0.048) than Holstein Friesian crosses (PP = 12.90%). Similarly, herds with more than 10 cattle (PP = 33.33%; OR = 4.167; p = 0.042) were found significantly at higher odds for seropositivity than herds having less than 10 cattle (PP = 10.71%). Due to the moderate prevalence of IBR among cattle in Nepal, this study recommends conducting additional planned research on IBR at the national level to safeguard the country's dairy businesses from potential financial losses.

Prevalence of serum immunoglobulin E against cross-reactive carbohydrate determinants in allergic and nonallergic horses, and its impact on polysensitisation in serum allergen tests.

The existence of antibodies against cross-reactive carbohydrate determinants (CCDs) has been studied extensively in humans, and more recently, in dogs and cats. These antibodies can reduce the specificity of in vitro serum allergen tests. To investigatethe prevalence of anti-CCDimmunoglobulin (Ig)E in both allergic and nonallergic horses as well as evaluateitspotential impact on serum allergen testing. Twenty-one allergic and 21 nonallergic horses. Sera were analysed for anti-CCD IgE utilising a commercial CHO enzyme-linked immunosorbent assay (ELISA). An allergen specific Fc-ε receptor ELISA then was performed to evaluate polysensitisation, both with and without the addition of a proprietary anti-CCD blocking solution. Antibodies against CCD were detected in 30 of 42 horses. There was no statistically significant difference (p=0.18) between the allergic and healthy groups in regard to anti-CCD prevalence. Horses with anti-CCD IgE exhibited more polysensitisation on serum allergen tests than horses without anti-CCD IgE in all allergen groups except mites. Polysensitisation was statistically significant at the 95% confidence interval for grasses (p <0.03), weeds (p=0.02) and stinging insects (p=0.0005). This was found to be true across both study groups. Inhibition with an anti-CCD blocking solution resulted in a 43% average reduction in polysensitisation. The prevalence of anti-CCD IgE of horses in this study coincides with the prevalence detected in pollen-sensitised people. Horses with anti-CCD IgE exhibited more positive reactions on serum allergen tests. By minimising potential artifactual polysensitisation, inclusion of an anti-CCD blocker may facilitate identification of allergen-specific IgE.

Potential of Polyethyleneimine as an Adjuvant To Prepare Long-Term and Potent Antifungal Nanovaccine

Background Candida albicans infections are particularly prevalent in immunocompromised patients. Even with appropriate treatment with current antifungal drugs, the mortality rate of invasive candidiasis remains high. Many positive results have been achieved in the current vaccine development. There are also issues such as the vaccine’s protective effect is not persistent. Considering the functionality and cost of the vaccine, it is important to develop safe and efficient new vaccines with long-term effects. In this paper, an antifungal nanovaccine with Polyethyleneimine (PEI) as adjuvant was constructed, which could elicit more effective and long-term immunity via stimulating B cells to differentiate into long-lived plasma cells.Materials and MethodsHsp90-CTD is an important target for protective antibodies during disseminated candidiasis. Hsp90-CTD was used as the antigen, then introduced SDS to “charge” the protein and added PEI to form the nanovaccine. Dynamic light scattering and transmission electron microscope were conducted to identify the size distribution, zeta potential, and morphology of nanovaccine. The antibody titers in mice immunized with the nanovaccine were measured by ELISA. The activation and maturation of long-lived plasma cells in bone marrow by nanovaccine were also investigated via flow cytometry. Finally, the kidney of mice infected with Candida albicans was stained with H&E and PAS to evaluate the protective effect of antibody in serum produced by immunized mice.ResultsNanoparticles (NP) formed by Hsp90-CTD and PEI are small, uniform, and stable. NP had an average size of 116.2 nm with a PDI of 0.13. After immunizing mice with the nanovaccine, it was found that the nano-group produced antibodies faster and for a longer time. After 12 months of immunization, mice still had high and low levels of antibodies in their bodies. Results showed that the nanovaccine could promote the differentiation of B cells into long-lived plasma cells and maintain the long-term existence of antibodies in vivo. After immunization, the antibodies in mice could protect the mice infected by C. albicans.ConclusionAs an adjuvant, PEI can promote the differentiation of B cells into long-lived plasma cells to maintain long-term antibodies in vivo. This strategy can be adapted for the future design of vaccines.

Research Advances on the Pathogenesis and Treatment of Hemolytic Uremic Syndrome --Review

Hemolytic uremic syndrome (HUS) is clinically rare, with high mortality and case fatality rates. In recent years, the research on HUS has been intensified and the pathophysiological mechanism has been continuously improved. At present, the main mechanism of pathogenesis is the excessive activation of complement alternative pathways mediated by complement-related gene mutations or the existence of antibodies. The treatment methods and strategies are also constantly updated, mainly including complement-blocking drugs such as Eculizumab, Lavalizumab, and Ravulizumab. In this review, the new developments in the pathogenesis and treatment of HUS is summarized, and provide references for the clinical treatment of HUS.

The Tip of Brucella O-Polysaccharide Is a Potent Epitope in Response to Brucellosis Infection and Enables Short Synthetic Antigens to Be Superior Diagnostic Reagents.

Brucellosis is a global disease and the world’s most prevalent zoonosis. All cases in livestock and most cases in humans are caused by members of the genus Brucella that possess a surface O-polysaccharide (OPS) comprised of a rare monosaccharide 4-deoxy-4-formamido-D-mannopyranose assembled with α1,2 and α1,3 linkages. The OPS of the bacterium is the basis for serodiagnostic tests for brucellosis. Bacteria that also contain the same rare monosaccharide can induce antibodies that cross-react in serological tests. In previous work we established that synthetic oligosaccharides, representing elements of the Brucella A and M polysaccharide structures, were excellent antigens to explore the antibody response in the context of infection, immunisation and cross reaction. These studies suggested the existence of antibodies that are specific to the tip of the Brucella OPS. Sera from naturally and experimentally Brucella abortus-infected cattle as well as from cattle experimentally infected with the cross-reactive bacterium Yersinia enterocolitica O:9 and field sera that cross react in conventional serological assays were studied here with an expanded panel of synthetic antigens. The addition of chemical features to synthetic antigens that block antibody binding to the tip of the OPS dramatically reduced their polyclonal antibody binding capability providing conclusive evidence that the OPS tip (non-reducing end) is a potent epitope. Selected short oligosaccharides, including those that were exclusively α1,2 linked, also demonstrated superior specificity when evaluated with cross reactive sera compared to native smooth lipopolysaccharide (sLPS) antigen and capped native OPS. This surprising discovery suggests that the OPS tip epitope, even though common to both Brucella and Y. enterocolitica O:9, has more specific diagnostic properties than the linear portion of the native antigens. This finding opens the way to the development of improved serological tests for brucellosis.

Neutralising Antibodies in Healthcare Workers after Two Doses of Covishield Vaccine at Three Months and Six Months: A Single-centre Observational Study

Introduction: The emergence of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) as a pandemic has put the global population at risk for its infection. It has also led to an accelerated effort to develop vaccines that can mitigate progression to severe infections at a minimum. The ambiguity about existence of antibodies in the human serum poses problem in formulating public health policies like suitable interval between doses of vaccines, appropriate time for vaccinating population, post natural infection, necessity of booster doses along with single dose. Aim: To estimate neutralising antibody level following vaccination of Healthcare Workers (HCWs) after three months and six months respectively. Materials and Methods: This was a prospective observational study performed in Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India after Institutional Ethics Committee (IEC) approval from January 2021 to February 2022. The study was conducted in 304 HCWs in the institute who had received two doses of Recombinant ChAdOx1 nCoV- 19 Corona Virus Vaccine (Covishield). 41 HCWs who were naturally infected with SARS-CoV-2 either before or after vaccination were also included. These participants were then subjected to IgG neutralising antibody titer estimation at three months and six months, postvaccination. Results: The study included 304 eligible HCWs. Majority of the participants belonged to the age group of 31-40 years (35.9%). Majority of the study participants were females (51%). Of the 304 participants, 263 were uninfected and 41 participants had been infected before and after vaccination. At the six month follow-up, it was observed that all but one HCW had seroconverted with majority of the participants showing more than 60% antibody level. Participants in the age group of 31-40 years showed the highest level and this observation was found to be statistically significant. Conclusion: Neutralising antibody response in HCWs is a key indicator of the efficacy of the vaccination program for Coronavirus Disease-2019 (COVID-19) in India.

The diagnostic benefit of antibodies against ribosomal proteins in systemic lupus erythematosus

BackgroundAnti-ribosomal P (anti-Rib-P) antibody is a specific serological marker for systemic lupus erythematosus (SLE) and routinely tested by targeting the common epitope of three ribosomal proteins of P0, P1 and P2. This study aimed to investigate if testing antibodies against individual ribosomal protein, but not the common epitope, is required to achieve the best diagnostic benefit in SLE.MethodsThe study included 82 patients with SLE and 22 healthy donors. Serum antibodies were determined by ELISA and immunoblot.ResultsThe prevalence of each antibody determined by ELISA was 35.4% (anti-Rib-P), 45.1% (anti-Rib-P0), 32.9% (anti-Rib-P1) and 40.2% (anti-Rib-P2) at 99% specificity, respectively. Of 53 patients with negative anti-Rib-P antibody, 21 (39.6%) were positive for anti-Rib-P0, 9 (17.0%) for anti-Rib-P1 and 12 (22.6%) for anti-Rib-P2 antibody. The positive rate of anti-Rib-P antibody detected by ELISA was close to the results by immunoblot (33.4%). Patients with any of these antibodies were featured by higher disease activity and prevalence of skin rashes than those with negative antibodies. Moreover, each antibody was particularly related to some clinical and laboratory disorders. The distribution of subclasses of IgG1–4 was varied with each antibody. Anti-Rib-P0 IgG1 and IgG3 were strongly correlated with disease activity and lower serum complement components 3 and 4.ConclusionsAnti-Rib-P antibody is not adequate to predict the existence of antibodies against ribosomal P0, P1 and P2 protein. The examination of antibodies against each ribosomal protein is required to achieve additional diagnostic benefit and to evaluate the association with clinical and serological disorders as well.

An Agent-Based Model of Infectious Diseases Taking into Account the Role of Immune Cells and Antibodies.

An agent-based infection model that takes into account the role of immune cells and antibodies has been constructed, and the effect of various factors on the spread and convergence of infection are analyzed. As a result, it was found that the calculated behavior of the numbers of newly infected, newly recovered, and the infected was qualitatively consistent with the actual phenomenon. It was found that an essential factor for the spread of infection is the number of infected persons with whom a healthy person encounters, while the existence of antibodies is not essential for the fundamental behavior of the spread and converge of infection. Based on these results, the fundamental mechanism for the spread of infection is that the probability of a healthy person encountering an infected person increases progressively, and the primary mechanism for convergence of the infection spread is that the above probability decreases progressively as the number of recovered people increases. It is considered that in order to control the spread of infection while minimizing economic deterioration, it is essential to identify infected persons, regulate their behavior, and minimize the probability for healthy persons encounter infected persons.

Post-vaccination rabies sero-survey in Georgia, 2015

ObjectiveThe objective of this survey was to study vaccination coverage andquality in dogs in Georgia through the detection of post-vaccinationantibodies.IntroductionRabies is endemic in Georgia with up to 100 confirmed cases inanimals per year. There is an estimated 350,000 domestic and straydogs/cats in Georgia. The prophylactic vaccination of domesticanimals against rabies was reestablished in Georgia in 2013. Each yearsince 2013, coverage has increased aiming to cover approximately70% of the total population of dogs/cats in Georgia.MethodsOnly vaccinated dog populations were included in the sero-survey. Using random selection, five locations were selected. Thesurvey was conducted over a period of 4-8 weeks after vaccination.In order to study vaccination coverage, the total dog population wasregistered. Samples were taken only from vaccinated dogs (confirmedby vaccination papers) and samples were sent to the Laboratory ofthe Ministry of Agriculture where they were tested for the presenceof antibodies using ELISA. Epidemiological information and GPScoordinates were recorded in the electronic integrated diseasesurveillance system (EIDSS) and geographic information system(GIS).ResultsOut of 572 dogs in sampled villages, 373 animal’s vaccination wasconfirmed leading to 65% vaccination coverage. Out of 255 samples,241 were suitable for testing; 237 samples (98.3%) were positive forthe existence of antibodies. Antibody titer was not measured.ConclusionsBased on the results of the survey, it can be seen that vaccinationcoverage is generally not high (65%) and needs improvement.The vaccination quality (as determined through the existence ofantibodies) is good (98.3%). In further surveys, antibody titersmust be measured in order to extract more information regardingvaccination quality.

Newcastle disease vaccines—A solved problem or a continuous challenge?

Newcastle disease (ND) has been defined by the World Organisation for Animal Health as infection of poultry with virulent strains of Newcastle disease virus (NDV). Lesions affecting the neurological, gastrointestinal, respiratory, and reproductive systems are most often observed. The control of ND must include strict biosecurity that prevents virulent NDV from contacting poultry, and also proper administration of efficacious vaccines. When administered correctly to healthy birds, ND vaccines formulated with NDV of low virulence or viral-vectored vaccines that express the NDV fusion protein are able to prevent clinical disease and mortality in chickens upon infection with virulent NDV. Live and inactivated vaccines have been widely used since the 1950’s. Recombinant and antigenically matched vaccines have been adopted recently in some countries, and many other vaccine approaches have been only evaluated experimentally. Despite decades of research and development towards formulation of an optimal ND vaccine, improvements are still needed. Impediments to prevent outbreaks include uneven vaccine application when using mass administration techniques in larger commercial settings, the difficulties associated with vaccinating free-roaming, multi-age birds of village flocks, and difficulties maintaining the cold chain to preserve the thermo-labile antigens in the vaccines. Incomplete or improper immunization often results in the disease and death of poultry after infection with virulent NDV. Another cause of decreased vaccine efficacy is the existence of antibodies (including maternal) in birds, which can neutralize the vaccine and thereby reduce the effectiveness of ND vaccines. In this review, a historical perspective, summary of the current situation for ND and NDV strains, and a review of traditional and experimental ND vaccines are presented.

Prevention of predicted neonatal isoerythrolysis with jaundice foal agglutination test in a newborn foal

This case report aims to highlight the utility of the jaundice foal agglutination (JFA) test used in the prevention of neonatal foal death caused by equine neonatal isoerythrolysis. The colostrum and the serum of a Friesian mare with repeated neonatal foal deaths and the whole blood of her newborn foal were tested for 5 days with the JFA test to detect a probable incompatibility. For the first 2 days, the JFA test gave a significantly positive reaction, indicating the existence of antibodies in the colostrum of the mare against the foal's erythrocyte antigens. The foal was not allowed access to her mother's colostrum and was fed with the frozen colostrum of other mares. At day 5, JFA test results were negative, indicating the disappearance of maternal antibodies from the colostrum.

The double‐edged sword of the immune system–a force for good or evil in the wound?

The double‐edged sword of the immune system–a force for good or evil in the wound?

Seroprevalence of Viral Upper Respiratory Infections in Dairy Cattle

Summary In this research, dairy cattle, located in Konya in Central Anatolian Region and its surrounding and had respiratory system symptoms, were investigated for the seroprevalence Infectious Bovine Rhinotracheitis (IBR), Bovine Viral Diarrhea Virus (BVDV), Bovine Respiratory Syncytial Virus (BRSV), Parainfluenza Virus type 3 (PI-3) and Bovine Adenovirus type 3 (BAV-3). For that purpose, 5800 animals, one year old and over, and bred in the private farms, were investigated and the blood samples were collected from 278 animals with respiratory system disease symptoms and high body temperatures. These samples were tested for presence of antibodies against IBR, BVDV, BRSV, PI-3 virus and BAV-3 by ELISA that was bought commercially. The seroprevalences which were determined for 5 viruses in cattle -(IBR, BVDV, BRSV, PI-3 virus and BAV-3)- were 35.25%, 96.04%, 94.40%, 92.80% and 85.97%, respectively. On the other hand, 0.35% (1 animal) of the dairy cattle sampled did not have any antibodies against the viruses. The existence of antibodies against the viruses were as such; 1.43% of cattle (4 animals) had antibodies against only one virus, 2.87% of cattle (8 animals) had antibodies against two, 14.02% of cattle (39 animals) had antibodies against three, 49.64% of cattle (138 animals) had antibodies against four and 31.65% of cattle (88 animals) had antibodies against five viruses. It was determined that IBR, BVDV, BRSV, PI-3 and BAV-3 infections were widespread and seroprevalences were high.

Isaacs' syndrome as a potassium channelopathy of the nerve.

Isaacs' syndrome (acquired neuromyotonia) is an antibody-mediated potassium channel disorder (channelopathy). The target channel proteins of the antigens are voltage-gated potassium channels (VGKCs), especially dendrotoxin-sensitive fast potassium channels. The suppression of voltage-gated outward K(+) current by antibodies induces hyperexcitability of the peripheral nerve. Patch clamp studies show that antibodies may not directly block the kinetics of VGKCs but may decrease channel density. Electrophysiological, pharmacological, and immunological findings indicate that the site of origin of spontaneous discharges is principally in the distal portion of the motor nerve and/or within the terminal arborization. The spectrum of potassium channelopathies is expanding. The existence of antibodies against VGKCs should be considered in patients who present with generalized nerve hyperexcitability of undetermined etiology.

Recognition by human monoclonal antibodies of free and complexed peptides representing the prefusogenic and fusogenic forms of human immunodeficiency virus type 1 gp41.

Human immunodeficiency virus type 1 (HIV-1) entry into target cells appears to be triggered when two heptad repeat regions in the ectodomain of gp41 associate, converting the prefusogenic form of gp41 to a fusogenic form. Peptides from these two heptad repeat regions, designated N51 and C43, form a coiled coil consisting of an alpha-helical trimer of heterodimers which approximates the core of the fusogenic form of gp41. To understand the antigenic structures of gp41 in these two configurations, and to examine the specificity of anti-gp41 antibodies produced by HIV-1-infected individuals, human anti-gp41 monoclonal antibodies (MAbs) were tested for their reactivity against N51, C43, and the complex formed by these peptides. Of 11 MAbs, 7 reacted with the complex but with neither of the parent peptides. These MAbs reacted optimally with the N51-C43 complex prepared at a 1:1 ratio and appeared to recognize the fusogenic form of gp41 in which the two heptad repeat regions are associated to form the coiled coil. The existence of antibodies from HIV-infected humans that exclusively recognize the N51-C43 complex constitutes the first proof that the coiled-coil conformation of gp41 exists in vivo and is immunogenic. Two of the 11 MAbs were specific for the hydrophilic loop region of gp41 and failed to react with either peptide alone or with the peptide complex, while the remaining 2 MAbs reacted with peptide C43. One of these two latter MAbs, 98-6, also reacted well with the equimolar N51-C43 complex, while reactivity with C43 by the other MAb, 2F5, was inhibited by even small amounts of N51, suggesting that the interaction of these peptides occludes or disrupts the epitope recognized by MAb 2F5. MAbs 98-6 and 2F5 are also unusual among the MAbs tested in their ability to neutralize multiple primary HIV isolates, although 2F5 displays more broad and potent activity. The data suggest that anti-gp41 neutralizing activity is associated with specificity for a region in C43 which participates in complex formation with N51.

Protein Fate in Neurodegenerative Proteinopathies: Polyglutamine Diseases Join the (Mis)Fold

Protein misfolding is now recognized to be a central feature of neurodegenerative diseases. Alzheimer disease (AD), Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), prion diseases, and the polyglutamine (polygln) diseases all represent proteinopathies—diseases in which a particular protein or set of proteins misfolds and aggregates. In the past decade, mutations have been identified in an increasing number of genes underlying specific forms of neurodegeneration—for example, genes encoding amyloid precursor protein (APP) and presenilins 1 and 2 in AD, parkin and alpha-synuclein in PD, Cu/Zn superoxide dismutase in ALS, tau in frontotemporal dementia, prion protein in Creutzfeldt-Jacob and Gerstmann-Straussler diseases, and at least eight different proteins in the polygln diseases (Hardy and GwinnHardy 1998; Price et al. 1998). Identification of these mutations was a first step in understanding the disease process; next, it will be necessary to explain how specific changes in disease proteins may alter the neuron’s physiology and to further question how neuronal responses to the mutant protein influence the disease process. This review examines the fate of mutant protein in neurons and the potential role of posttranslational events in pathogenesis, with particular focus on the polygln diseases. Posttranslational events have already been implicated

Studies on the relationship between anaphylactoid purpura and human parvovirus B19

Human parvovirus B19 (B19) has been shown to be the cause of erthema infectiousum (EI). Recently the various clinical manifestations with B19 infection are coming to light. The relationship between B19 and anaphylactoid purpura (Schölein-Henoch purpura: SHP) was investigated in a retrospective study. There were sixteen patients (male 9, female 7, average age 6.0 +/- 1.7) who were diagnosed as SHP. Serum specimens were used in the present study. Specific IgM and IgG were assayed by enzyme immunoassay, B19 DNA was assayed by polymerase chain reaction (PCR). Five of the sixteen patients were positive for B19 DNA assayed by PCR, three were positive for B19 IgM in the acute phase. Kidney involvement appeared in one case with B19 infection and in two cases without infection. Abdominal involvement appeared in one case with infection and in three cases without. In this study, five of the sixteen patients had evidence of recent B19 infection by the existence of antibodies and PCR method. In conclusion, it is necessary to investigate the B19 infection with or without EI in the cases of SHP.