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1.
Linking chronic wasting disease to scrapie by comparison of Spiroplasma mirum ribosomal DNA sequences 总被引:2,自引:0,他引:2
Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative diseases of man and animals and are transmitted by a filterable pathogen whose identity is currently unresolved. Our data indicates that Spiroplasma, a wall-less bacterium, is involved in the pathogenesis of TSE. We searched for Spiroplasma ribosomal gene sequences in 10 scrapie-infected sheep brains and 10 normal sheep brains, 7 cervid samples infected with chronic wasting disease (CWD), and 7 normal cervid brains. DNA was extracted from these tissue samples and amplified by polymerase chain reaction (PCR) using primers specific for Spiroplasma-specific 16S rDNA. Specificity of the amplicon was determined by Southern blotting and DNA sequence analyses. Spiroplasma 16S rDNA was found in 8 of 10 scrapie-infected sheep brains and 6 of 7 CWD-infected tissue samples. All normal animal brain samples were negative. Spiroplasma 16S rDNA was also found in two human Creutzfeldt-Jakob diseased (CJD) brains but not in two age-matched normal human brains. DNA sequence analyses of the amplified PCR products from human and animal TSE cases revealed greater than 99% nucleotide sequence homology with Spiroplasma mirum. The presence of Spiroplasma DNA in TSE-infected tissues supports our hypothesis that Spiroplasma may be involved in the pathogenesis of these diseases. 相似文献
2.
Hamir AN Kunkle RA Nicholson EM Miller JM Hall SM Schoenenbruecher H Brunelle BW Richt JA 《Journal of comparative pathology》2008,138(2-3):121-130
To determine the transmissibility of chronic wasting disease (CWD) to fallow deer (Dama dama) and to provide information about clinical course, lesions and suitability of currently used diagnostic procedures for detection of CWD in this species, 13 fawns were inoculated intracerebrally with CWD brain suspension from elk (n=6) or white-tailed deer (n=7). Three other fawns were kept as uninfected controls. Three CWD-inoculated deer were killed 7.6 months post-inoculation (mpi). None had abnormal prion protein (PrPd) in their tissues. One sick deer died at 24 mpi and one deer without clinical signs was killed at 26 mpi. Both animals had a small focal accumulation of PrPd in the midbrain. Between 29 and 37 mpi, three other deer became sick and were killed. All had shown gradual decrease in appetite and some loss of body weight. Microscopical lesions of spongiform encephalopathy were not observed, but PrPd was detected in tissues of the central nervous system (CNS) by immunohistochemistry, western blot and by two commercially available rapid diagnostic tests. This study demonstrates that intracerebrally inoculated fallow deer amplified CWD PrPd from white-tailed deer and elk in the absence of lesions of spongiform encephalopathy. Four years after CWD inoculation, the remaining five inoculated and two control deer are alive and apparently healthy. 相似文献
3.
Experimental chronic wasting disease (CWD) in the ferret 总被引:1,自引:0,他引:1
Sigurdson CJ Mathiason CK Perrott MR Eliason GA Spraker TR Glatzel M Manco G Bartz JC Miller MW Hoover EA 《Journal of comparative pathology》2008,138(4):189-196
Chronic wasting disease (CWD), a prion disease of North American deer, elk and moose, affects both free-ranging and captive cervids. The potential host range for CWD remains uncertain. The susceptibility of the ferret to CWD was examined experimentally by administering infectious brain material by the intracerebral (IC) or oral (PO) route. Between 15 and 20 months after IC inoculation, ferrets developed neurological signs consistent with prion disease, including polyphagia, somnolence, piloerection, lordosis and ataxia. Upon first sub-passage of ferret-adapted CWD, the incubation period decreased to 5 months. Spongiform change in the neuropil was most marked in the basal ganglia, thalamus, midbrain and pons. The deposition of PrP(CWD) was granular and was occasionally closely associated with, or localized within, neurons. There were no plaque-like or perivascular PrP aggregates as seen in CWD-infected cervids. In western blots, the PrP(CWD) glycoform profile resembled that of CWD in deer, typified by a dominant diglycosylated glycoform. CWD disease in ferrets followed IC but not PO inoculation, even after 31 months of observation. These findings indicate that CWD-infected ferrets share microscopical and biochemical features of CWD in cervids, but appear to be relatively resistant to oral infection by primary CWD inoculum of deer origin. 相似文献
4.
《Journal de Mycologie Médicale》2020,30(3):101009
Chronic renal disease patients under chronic dialysis (CRDD) have a multifactorial immunological deterioration with an increased risk of Candida infections. Incidence of Candida infections is increasing. Choice of suitable antifungal agents is limited due to the resistance of some species to several antifungals. Aim of the present study was to identify the distribution and antifungal susceptibility patterns of oral isolated Candida species from infected and colonized patients, as well as to investigate the risk factors for oral infection in patients on dialysis. Cross-sectional study, approved by the institutional bioethics committees was performed in CRDD patients. Demographic, clinic data, and oral mucosa samples were obtained. Infection diagnosis was established clinically and confirmed with exfoliative cytology, each sample was plated on CHROMagar Candida and incubated at 36 °C for 2 days. Yeast species were identified by carbohydrate assimilation ID 32 C AUX system and the apiweb database. For the antifungal susceptibility test, the M44 A-3 method (CLSI) using fluconazole (FCZ), miconazole (MCZ), nystatin (NYS), and voriconazole (VCZ). Study included 119 participants, the main cause of CRD was nephropathy due to DM2 (58%), and three-fourths of the patients were under hemodialysis. Candida prevalence was 56.3% of 67 colonized or infected patients, 88 isolates were obtained. Principal identified species were C. albicans (51.1%), C. glabrata (25%), and C. tropicalis (14.8%). C. glabrata showed a reduced response to FCZ in 50% of isolates and C. albicans had a reduced response in 16% of the isolates. Antifungal agent with the least efficacious response or with the lowest susceptibility in the isolates of these patients was MCZ, followed by VCZ and FCZ, whereas NYS induced the best antifungal response. 相似文献
5.
Our previous studies have shown that the persistent expression of Borna disease virus phosphoprotein (BDV P) in mice leads to behavioral abnormalities resembling those in BDV-infected animals. In this study, we investigated whether the neurobehavioral abnormalities genetically induced by BDV P influence experimental prion disease. The effect of the phosphoprotein on prion diseases was evaluated based on the incubation time and survival curve, as well as the abnormal isoform of prion protein (PrP(Sc)) levels in brains of BDV P Tg mice treated with proteinase K (PK) treatment and subjected to western blotting. Increased expression of the BDV P transgene had no effect on the PrP(Sc) level, incubation time, or survival curve. The abnormalities induced by BDV P are different from those induced by prion diseases, indicating that the signaling cascades induced by the phosphoprotein differ from those induced by prion diseases. 相似文献
6.
Raffaele D'Amelio Paolo Bellavite Paolo Bianco Pasquale De Sole Soccorsa Le Moli Silvio Lippa Rosalba Seminara Brunella Vercelli Filippo Rossi Giovanni Rocchi Fernando Aiuti 《Journal of clinical immunology》1984,4(3):220-227
Two sisters with chronic granulomatous disease (CGD) have been studied. The diagnosis was suggested by the histopathological findings from the spleen and lymph nodes of the proband and confirmed by the low values obtained in the following tests performed on polymorphonuclear leukocytes (PMN): chemiluminescence, nitroblue tetrazolium (NBT) reduction, killing ofStaphylococcus aureus, and O
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production. NADPH oxidase activity was not detected in the homogenates of the patients' PMN but cytochromeb was normally present. In addition, PMN depolarization induced by phorbol-myristate acetate was absent, thus suggesting a defect of the activation mechanism of the respiratory enzyme. The normal depolarization induced by ouabain indicated that the membrane polarity regulated by the Na/K pump in the patients' cells was not affected. The low, but not completely absent, respiratory activity of the patients' PMN could suggest an X-linked mode of inheritance with incomplete Lyonization. From a clinical point of view, one sister had mild symptoms whereas the other was almost symptomless, thus confirming once more the heterogeneity of CGD syndrome. 相似文献
7.
Goñi F Prelli F Schreiber F Scholtzova H Chung E Kascsak R Brown DR Sigurdsson EM Chabalgoity JA Wisniewski T 《Neuroscience》2008,153(3):679-686
Significant outbreaks of prion disease linked to oral exposure of the prion agent have occurred in animal and human populations. These disorders are associated with a conformational change of a normal protein, PrPC (C for cellular), to a toxic and infectious form, PrPSc (Sc for scrapie). None of the prionoses currently have an effective treatment. Some forms of prion disease are thought to be spread by oral ingestion of PrPSc, such as chronic wasting disease and variant Creutzfeldt-Jakob disease. Attempts to obtain an active immunization in wild-type animals have been hampered by auto-tolerance to PrP and potential toxicity. Previously, we demonstrated that it is possible to overcome tolerance and obtain a specific anti-PrP antibody response by oral inoculation of the PrP protein expressed in an attenuated Salmonella vector. This past study showed that 30% of vaccinated animals were free of disease more than 350 days post-challenge. In the current study we have both optimized the vaccination protocol and divided the vaccinated mice into low and high immune responder groups prior to oral challenge with PrPSc scrapie strain 139A. These methodological refinements led to a significantly improved therapeutic response. 100% of mice with a high mucosal anti-PrP titer immunoglobulin (Ig) A and a high systemic IgG titer, prior to challenge, remained without symptoms of PrP infection at 400 days (log-rank test P<0.0001 versus sham controls). The brains from these surviving clinically asymptomatic mice were free of PrPSc infection by Western blot and histological examination. These promising findings suggest that effective mucosal vaccination is a feasible and useful method for overcoming tolerance to PrP and preventing prion infection via an oral route 相似文献
8.
Haiying Wang Jiayu Wan Wei Wang Dongxu Wang Sha Li Peng Liao Zhuo Hao Songbo Wu Jing Xu Nan Li Hongsheng OuYang Hongwei Gao 《Neuroscience letters》2011
Shadoo is a glycoprotein expressed in the adult brain that is an interacting protein of prion protein; however, its function remains to be determined. To elucidate its role in prion pathogenesis, we generated transgenic mice overexpressing wild-type (wt) Shadoo driven by the murine PrP promoter. Expression of the murine Sprn transgene significantly increased brain Shadoo protein levels in all three mouse lines generated. Following infection with mouse-adapted scrapie strain 22L, all transgenic mice tested exhibited characteristics of scrapie disease. Importantly, there was no correlation between the expression level or incubation time of Shadoo with disease phenotype. We therefore conclude that Shadoo has little or no influence on the outcome of transmissible spongiform encephalopathy (TSE) disease in transgenic mice. 相似文献
9.
Chronic kidney disease has a significant worldwide prevalence affecting 7.2% of the global adult population with the number dramatically increasing in the elderly. Although the causes are various, diabetes is the most common cause of CKD in the United States and an increasing cause of the same worldwide. Therefore, we chose to focus on diabetic chronic kidney disease in this review. The pathogenesis is multifactorial involving adaptive hyperfiltration, advanced glycosylated end-product synthesis (AGES), prorenin, cytokines, nephrin expression and impaired podocyte-specific insulin signaling. Treatments focus on lifestyle interventions including control of hyperglycemia, hypertension and hyperlipidemia as well treatment of complications and preparation for renal replacement therapy. This review examines the current literature on the epidemiology, pathogenesis, complications and treatment of CKD as well as possible areas of future disease intervention. 相似文献
10.
Kang EM Marciano BE DeRavin S Zarember KA Holland SM Malech HL 《The Journal of allergy and clinical immunology》2011,127(6):1319-1326
Chronic granulomatous disease (CGD) still causes significant morbidity and mortality. The difficulty in considering high-risk yet curative treatments, such as allogeneic bone marrow transplantation, lies in the unpredictable courses of both CGD and bone marrow transplantation in different patients. Some patients with CGD can have frequent infections, granulomatous or autoimmune disorders necessitating immunosuppressive therapy, or both but also experience long periods of relative good health. However, the risk of death is clearly higher in patients with CGD of all types, and the complications of CGD short of death can still cause significant morbidity. Therefore, with recent developments and improvements, bone marrow transplantation, previously considered an experimental or high-risk procedure, has emerged as an important option for patients with CGD. We will discuss the complications of CGD that result in significant morbidity and mortality, particularly the most common infections and autoimmune/inflammatory complications, as well as their typical management. We will then discuss the status of bone marrow transplantation. 相似文献
11.
12.
人源轮状病毒转基因马铃薯口服免疫小鼠的免疫应答研究 总被引:2,自引:0,他引:2
目的分析人源轮状病毒转基因植物抗原的口服免疫应答反应。方法在根癌脓杆菌介导获得系列转基因马铃薯植株的基础上,用ELISA分析转基因马铃薯中目的蛋白表达水平。马铃薯块茎直接口服免疫Balb/c小鼠,ELISA分析免疫小鼠血清、唾液、粪便提取物特异抗体水平。结果获得一株最高表达量的转化株;口服免疫可诱导较强的血清IgG反应和强烈的黏膜sIgA反应,粪便的sIgA最高,唾液次之,尿液中无sIgA;加霍乱毒素B亚单位(CTB)佐剂免疫组小鼠和霍乱毒素(CT)佐剂免疫组小鼠抗体水平无显著差异,无佐剂免疫组小鼠抗体水平略低。结论人源轮状病毒转基因植物疫苗联合黏膜佐剂免疫动物可诱导特异的系统与黏膜免疫应答,且黏膜免疫强度略高于系统免疫。 相似文献
13.
Social transmission of food preference (STFP) is a test of olfactory memory that can be used in mice. Confounds in STFP that can lead to misinterpretation of an STFP deficit as a memory impairment include changes in social interaction and olfaction. The issue of changes in social interaction was addressed by evaluating an observer-centric and a demonstrator-centric method for scoring the interaction phase of STFP in mice. The demonstrator-centric method was applied to a line of STFP-impaired, galanin-overexpressing transgenic (GAL-tg). GAL-tg mice were impaired in STFP without deficits in social interaction. In tests of olfactory ability, GAL-tg mice were unimpaired on buried-food and habituation-dishabituation tasks. The current studies describe an expanded method for using STFP in mice and confirm a deficit in olfactory memory in GAL-tg mice. 相似文献
14.
Santhi WS Sebastian P Varghese BT Prakash O Pillai MR 《Experimental and molecular pathology》2006,81(2):123-130
Oral cancer is a major health problem in many parts of the world including India. The molecular mechanisms involved in oral tumorigenesis are not completely understood. Although surgery continues to be the most common treatment modality for this cancer, survival rates of oral cancer patients have still not significantly improved over the last few decades. Classical diagnostic methods are still not sensitive enough in detecting completeness of surgery and assessing minimal residual disease. This study investigated the role of NF-kappaB and COX-2 both in oral cancer progression and assessment of minimal residual disease. Expression of NF-kappaB proteins and its inhibitory protein IkappaB-alpha was evaluated using immunohistochemistry, ELISA and EMSA, while RT-PCR was used to detect COX-2 expression. Cytoplasmic expression as well as nuclear translocation of NF-kappaB proteins increased with histological progression of oral cancer (from normal to leukoplakia to cancer). A similar pattern of expression was observed for COX-2 also. NF-kappaB proteins, both cytoplasmic and nuclear, had a significant negative correlation from tumor to surgical margin to extra margin; COX-2 paralleled the expression of NF-kappaB proteins. Our results thus point to NF-kappaB and COX-2 as participants in oral tumor progression and also to the validation of these two molecular markers in assessing minimal residual disease. 相似文献
15.
Tzu-Wei Wei Ching-Feng Lien Tun-Yen Hsu Hong-Lin He 《International journal of clinical and experimental pathology》2015,8(7):8628-8631
Chronic sclerosing sialadenitis typically involves the submandibular gland. It usually occurs in the middle-aged and elderly adults with a slight male predominance. Recent evidences have suggested that it is an entity of IgG4-related sclerosing disease and has distinct histopathological features, such as a dense lymphoplasmacytic infiltrate, sclerosis and obliterative phlebitis. It is important to discriminate this entity from other diseases, trying to give effective treatment to the patients. In this report, we described a patient having chronic sclerosing sialadenitis in the submandibular gland. 相似文献
16.
John L. Pilon Paul B. Nash Terry Arver Don Hoglund Kurt C. VerCauteren 《Journal of virological methods》2009,161(1):168-172
Two serine protease enzymes, subtilisin 309 and subtilisin 309-v, were used to digest brain homogenates containing high levels of prion infectivity using mildly alkaline conditions to investigate prion decontamination methods. To establish that PrPres infectivity was eliminated, we utilized the Rocky Mountain Laboratory (RML) mouse-adapted scrapie model system for bioassay. Only one digestion condition (subtilisin 309 at 138 mAU/ml, 55 °C and 14 h digestion time pH 7.9) was considered to be highly relevant statistically (P < 0.001) compared to control, with 52% of challenged mice surviving until the end of the study period. In contrast, treatment of PrPres by autoclaving at 134 °C or treatment with hypochlorite at a concentration of 20,000 ppm completely protected mice from prionosis. Further, in vitro assays suggest that potential proteolytic based PrPres decontamination methods must use high enzyme concentration, pH values >9.0, and elevated temperatures to be a safely efficacious, thereby limiting applicability on delicate surgical instruments and use in the environment. 相似文献
17.
Arne Burkhardt Ingeborg R. Bos Thomas Löning Jan -Olaf Gebbers Herwart F. Otto Gerhard Seifert 《Virchows Archiv : an international journal of pathology》1979,384(2):223-244
Summary Non-epithelial mesenchymal and neuroectodermal cells occur between the keratinocytes in the stratified squamous epithelium of the oral mucosa. These cells cannot be classified adequately by light microscopy. In the present study the oral mucosa of the lip, cheek and tongue of 50 mice were studied by light and electron microscopy. 3,025 mononuclear interepithelial cells were documented and analysed.Monocytogenic macrophages, plasma cells and mast cells were not found interepithelially and cannot be regarded as a regular constituent of the epithelium. Only a few neuroectodermal cells — in mice these are exclusively Merkel cells, with no melanocytes — were localized in the epithelium. The majority of the interepithelial cell population is made up of lymphocytes (22.8%) and Langerhans cells (56.8%). They are an integral constituent of the epithelium. Lymphocytes with rounded and indented nuclei can be identified. The larger and dendritic Langerhans cells are a specific cell of squamous epithelium and also occur in the oral mucosa. Not all cells which feature the cytological characteristics of Langerhans cells contain Langerhans or Birbeck granules. Accordingly these granules cannot be considered an exclusive identification characteristic. Two types of Langerhans cells can be differentiated. 80.9% have the more or less typical appearance known from the epidermis and were termed macrophagocytoid Langerhans cells. The nuclei are irregularly indented and moderately heterochromatic. 19.1% possessed conspicuous large, spherical, euchromatic nuclei and an electron-lucent cytoplasm. These were termed reticuloid Langerhans cells. About 20% of the interepithelial cell population could not be identified, neither as typical lymphocytes nor as Langerhans cells. These were small to medium sized cells with deeply indented cerebriform strongly heterochromatic nuclei. They are similar to the Sézary cells or mycosis fungoides cells of epidermotropic human T-cell lymphomas. The lymphocytic nature of these cells has been confirmed. It seems likely that differentiation of lymphocytes to cerebriform cells occurs within the epithelium. It is further discussed whether cerebriform cells are precursors of Langerhans cells, a conclusion suggested morphologically by transitional forms. This would imply that Langerhans cells originate from lymphocytes, and that the cerebriform cell is an intermediate step of differentiation. The microenvironment of the squamous epithelium may play a role in the process of differentiation, which could explain the epitheliotropy of lymphocytes. The possibility is considered that Langerhans cells and interdigitating reticulum cells of the T-cell area of lymph nodes are identical. The close functional cooperation of Langerhans cells, lymphocytes, and interdigitating reticulum cells in immunological defenses against external antigens is discussed.The authors wish to express their sincere appreciation to Miss P. Starck and Miss I. Brandt for invaluable technical assistance in this project. 相似文献
18.
Cyril Desvignes Hlne Bour Jean-Franois Nicolas Dominique Kaiserlian 《European journal of immunology》1996,26(8):1756-1761
Oral tolerance is defined by immune unresponsiveness after oral administration of soluble antigens and by antigen-specific inhibition of peripheral immune responses induced by prior antigen feeding. The aim of this study was to investigate the implication of the major histocompatibility complex (MHC) class II presentation pathway to CD4+ T cells in oral tolerance of contact sensitivity (CS) to the hapten dinitrofluorobenzene (DNFB). We used MHC class II knockout (ABº/º) and invariant chain knockout (Iiº/º) mice, which have, respectively, a total or partial defect in class II-restricted activation of CD4+ T cells, as well as normal C57BL/6 mice depleted of CD4+ T cells by injection of a specific antibody. Intragastric administration of DNFB prior to skin sensitization induced specific inhibition of contact sensitivity to DNFB in Aβ+/º and Ii+/º heterozygotes comparable to that observed in C57BL/6 mice. In contrast, no oral tolerance was observed in either MHC class II-deficient Aβº/º and Iiº/º homozygote mutants or in syngeneic anti-CD4-depleted C57BL/6 mice. Moreover, a single oral administration of DNFB, without skin sensitization, could prime Aβº/º, Iiº/º as well as anti-CD4-depleted C57BL/6 mice for DNFB-specific CS. These findings demonstrate that the class II/CD4 pathway is involved in oral tolerance manifested both as the inhibition of CS by hapten feeding prior to skin sensitization, and as immune unresponsiveness of normal mice to oral administration of hapten. Furthermore, our data provide evidence that a single oral feeding with DNFB is able to prime mice for hapten-specific CS, provided that the class II/CD4 pathway is bypassed. 相似文献
19.
Beeri Rachel; Gnatt Averell; Lapidot-Lifson Yaron; Ginzberg Dalia; Shani Moshe; Soreq Hermona; Zakut Haim 《Human reproduction (Oxford, England)》1994,9(2):284-292
Gene amplification occurs frequently in tumour tissues yet is,in general, non-inheritable. To study the molecular mechanismsconferring this restraint, we created transgenic mice carryinga human butyrylcholinesterase (BCHE) coding sequence, previouslyfound to be amplified in a father and son. Blot hybridizationof tail DNA samples revealed somatic transgene amplificationswith variable restriction patterns and intensities, suggestingthe occurrence of independent amplification events, in 31% (11/35)of mice from the FII generation but in only 3.5% (2/58) of theFII and FIV generations. In contrast, >10-fold amplificationsof the BCHE transgene and the endogenous acetylcholinesteraseand c-raf genes appeared in both testis and epididymis DNA from>80% of FIII mice. Drastic, selective reductions in testisBCHEmRNA but not in actin mRNA were detected by the PCR amplificationof testis cDNA from the transgenic mice, and apparently resultedin the limited transmission of amplified genes. The testicularamplification of the BCHE transgene may potentially representa general phenomenon with clinical implications in human infertility. 相似文献
20.
Jannot AS Amiel J Pelet A Lantieri F Fernandez RM Verheij JB Garcia-Barcelo M Arnold S Ceccherini I Borrego S Hofstra RM Tam PK Munnich A Chakravarti A Clerget-Darpoux F Lyonnet S 《European journal of human genetics : EJHG》2012,20(9):917-920
Hirschsprung disease (HSCR, aganglionic megacolon) is a complex and heterogeneous disease with an incidence of 1 in 5000 live births. Despite the multifactorial determination of HSCR in the vast majority of cases, there is a monogenic subgroup for which private rare RET coding sequence mutations with high penetrance are found (45% of HSCR familial cases). An asymmetrical parental origin is observed for RET coding sequence mutations with a higher maternal inheritance. A parent-of-origin effect is usually assumed. Here we show that a differential reproductive rate for males and females also leads to an asymmetrical parental origin, which was never considered as a possible explanation till now. In the case of HSCR, we show a positive association between penetrance of the mutation and parental transmission asymmetry: no parental transmission asymmetry is observed in sporadic RET CDS mutation carrier cases for which penetrance of the mutation is low, whereas a parental transmission asymmetry is observed in affected sib-pairs for which penetrance of the mutation is higher. This allows us to conclude that the explanation for this parental asymmetry is that more severe mutations have resulted in a differential reproductive rate between male and female carriers. 相似文献