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1.
mSphere ; : e0046624, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39136454

RESUMO

The cyst wall of the eye pathogen Acanthamoeba castellanii contains cellulose and has ectocyst and endocyst layers connected by conical ostioles. Cyst walls contain families of lectins that localize to the ectocyst layer (Jonah) or the endocyst layer and ostioles (Luke and Leo). How lectins and an abundant laccase bind cellulose and why proteins go to locations in the wall are not known and are the focus of the studies here. Structural predictions identified ß-jelly-roll folds (BJRFs) of Luke and sets of four disulfide knots (4DKs) of Leo, each of which contains linear arrays of aromatic amino acids, also present in carbohydrate-binding modules of bacterial and plant endocellulases. Ala mutations showed that these aromatics are necessary for cellulose binding and proper localization of Luke and Leo in the Acanthamoeba cyst wall. BJRFs of Luke, 4DKs of Leo, a single ß-helical fold (BHF) of Jonah, and a copper oxidase domain of the laccase each bind to glycopolymers in both layers of deproteinated cyst walls. Promoter swaps showed that ectocyst localization does not just correlate with but is caused by early encystation-specific expression, while localization in the endocyst layer and ostioles is caused by later expression. Evolutionary studies showed distinct modes of assembly of duplicated domains in Luke, Leo, and Jonah lectins and suggested Jonah BHFs originated from bacteria, Luke BJRFs share common ancestry with slime molds, while 4DKs of Leo are unique to Acanthamoeba.IMPORTANCEAcanthamoebae is the only human parasite with cellulose in its cyst wall and conical ostioles that connect its inner and outer layers. Cyst walls are important virulence factors because they make Acanthamoebae resistant to surface disinfectants, hand sanitizers, contact lens sterilizers, and antibiotics applied to the eye. The goal here was to understand better how proteins are targeted to specific locations in the cyst wall. To this end, we identified three new proteins in the outer layer of the cyst wall, which may be targets for diagnostic antibodies in corneal scrapings. We used structural predictions and mutated proteins to show linear arrays of aromatic amino acids of two unrelated wall proteins are necessary for binding cellulose and proper wall localization. We showed early expression during encystation causes proteins to localize to the outer layer, while later expression causes proteins to localize to the inner layer and the ostioles.

2.
Arch Orthop Trauma Surg ; 144(6): 2691-2701, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38700675

RESUMO

INTRODUCTION: The optimal arthroscopic management for popliteal cyst decompression remains uncertain, with ongoing debate between preserving the cyst wall or completely removing it. The purpose of this study is to compare the outcomes and complications of arthroscopic popliteal cyst decompression with cyst wall preservation and cyst wall resection. METHODS: A systematic review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines was conducted. It encompassed studies that focused on arthroscopic popliteal cyst decompression, considering both cyst wall preservation and cyst wall resection. The quality assessment of the included studies was carried out using the Methodology Index for Non-Randomized Research criteria. Following this, meta-analyses were conducted, employing odds ratios (ORs) for dichotomous outcomes and calculating mean differences (MDs) for continuous outcomes. RESULTS: Four articles included a collective of 214 knees. Each of these studies presented level 3 evidence. The comparison between the cyst wall preservation group and the cyst wall resection group revealed similar clinical outcomes based on the Rauschning and Lindgren grade (grade 0 [OR = 0.66, 95% CI: 0.37-1.19, p = 0.17]; grade I [OR = 1.33, 95% CI: 0.66-2.67, p = 0.43]; grade II [OR = 1.39, 95% CI: 0.46-4.14, p = 0.56]; grade III [OR = 3.46, 95% CI: 0.13-89.95, p = 0.46]) and Lysholm score (MD = 0.83, 95% CI: -0.65-2.32, p = 0.27). However, MRI results indicated a significant improvement in the cyst wall resection group (cyst disappearance [OR = 0.50, 95% CI: 0.28-0.90, p = 0.02]; cyst shrinkage or decrease in size [OR = 1.41, 95% CI: 0.78-2.55, p = 0.26]; cyst persistence or recurrence [OR = 7.63, 95% CI: 1.29-45.08, p = 0.02]). Nevertheless, the operative time for cyst resection was significantly longer compared to cyst preservation (MD = -14.90, 95% CI: -21.96 - -7.84, p < 0.0001), and the cyst wall resection group experienced significantly higher complications than the cyst wall preservation group (OR = 0.24, 95% CI: 0.06 to 1.02, p = 0.05). CONCLUSION: During arthroscopic popliteal cyst decompression, cyst wall resection led to longer operative times and higher complication rates but lower recurrence rates and better MRI outcomes. The functional outcomes after surgery were found to be similar.


Assuntos
Artroscopia , Descompressão Cirúrgica , Cisto Popliteal , Humanos , Artroscopia/métodos , Cisto Popliteal/cirurgia , Descompressão Cirúrgica/métodos , Resultado do Tratamento
3.
Genes (Basel) ; 14(9)2023 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-37761895

RESUMO

α-1,2-mannosyltransferase (ALG9) germline variants are linked to autosomal dominant polycystic kidney disease (ADPKD). Many individuals affected with ADPKD possess polycystic livers as a common extrarenal manifestation. We performed whole exome sequencing in a female with autosomal dominant polycystic liver disease (ADPLD) without kidney cysts and established the presence of a heterozygous missense variant (c.677G>C p.(Gly226Ala)) in ALG9. In silico pathogenicity prediction and 3D protein modeling determined this variant as pathogenic. Loss of heterozygosity is regularly seen in liver cyst walls. Immunohistochemistry indicated the absence of ALG9 in liver tissue from this patient. ALG9 expression was absent in cyst wall lining from ALG9- and PRKCSH-caused ADPLD patients but present in the liver cyst lining derived from an ADPKD patient with a PKD2 variant. Thus, heterozygous pathogenic variants in ALG9 are also associated with ADPLD. Somatic loss of heterozygosity of the ALG9 enzyme was seen in the ALG9 patient but also in ADPLD patients with a different genetic background. This expanded the phenotypic spectrum of ADPLD to ALG9.


Assuntos
Cistos , Hepatopatias , Rim Policístico Autossômico Dominante , Humanos , Feminino , Rim Policístico Autossômico Dominante/genética , Hepatopatias/genética , Hepatopatias/patologia , Cistos/genética , Manosiltransferases , Proteínas de Membrana/genética
4.
Pathogens ; 13(1)2023 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-38251328

RESUMO

The "Wattle and Daub" model of cyst wall formation in Entamoeba invadens has been used to explain encystment in Entamoeba histolytica, the causal agent of amoebiasis, and this process could be a potential target for new antiamoebic drugs. In this study, we studied the morphological stages of chitin wall formation in E. invadens in more detail using fluorescent chitin-binding dyes and the immunolocalization of cyst wall proteins. It was found that chitin deposition was mainly initiated on the cell surface at a specific point or at different points at the same time. The cystic wall grew outward and gradually covered the entire surface of the cyst over time, following the model of Wattle and Daub. The onset of chitin deposition was guided by the localization of chitin synthase 1 to the plasma membrane, occurring on the basis of the Jacob lectin in the cell membrane. During encystation, F-actin was reorganized into the cortical region within the early stages of encystation and remained intact until the completion of the chitin wall. The disruption of actin polymerization in the cortical region inhibited proper wall formation, producing wall-less cysts or cysts with defective chitin walls, indicating the importance of the cortical actin cytoskeleton for proper cyst wall formation.

5.
Pediatric Health Med Ther ; 13: 361-365, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386041

RESUMO

Hydatidosis is a parasitic disease caused by Echinococcus granulosus, which affects children in many different parts of the world. It commonly affects the lungs and the liver of the children. Brain hydatidosis is an extremely rare clinical condition in the pediatric population, presenting with non-specific symptoms and signs. The diagnosis of intracranial hydatid cysts can be established by brain magnetic resonance imaging and histopathological examination of the specimen. Here, we report an 8-year-old female child diagnosed with a temporoparietal brain hydatid cyst. Brain magnetic resonance imaging showed a thin-walled cystic lesion located in the right temporoparietal lobe with significant mass effect and midline shift, with no abnormal wall or solid enhancement, and no surrounding edema. The diagnosis of brain temporoparietal hydatid cyst was made radiologically. The patient was operated on and the cyst was completely removed without rupture. The removed cyst was sent for histopathological examination; the histological sections showed a laminated acellular cyst wall with a nucleated germinal layer and no protoscolices, and the diagnosis of temporoparietal brain hydatid cyst was confirmed. The patient had a smooth postoperative course, started albendazole therapy, and was discharged with improvement.

6.
Front Vet Sci ; 9: 1033380, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36311681

RESUMO

Toxoplasma gondii is commonly transmitted among animals and humans by ingestion of infected animal tissues or by consumption of food and water contaminated with environmentally-resistant oocysts excreted by cats. Tissue cysts and oocysts have different walls, whose structures and compositions are poorly known. Herein, we describe an immunomagnetic separation (IMS) method that was successfully used for purification of T. gondii tissue cysts generated in cell culture. We used an IgG monoclonal antibody (mAb) that reacts against antigens in tissue cyst walls. Many in vitro produced cysts were obtained by this IMS; >2,000 T. gondii cysts were isolated from a single culture flask of 25 cm2. Tissue cysts from two Hammondia spp., H. hammondi, and H. heydorni, produced in cell culture were also separated using this method. As a reference, purification of tissue cysts by Percoll gradients was used. Percoll was able to separate T. gondii tissue cysts produced in mice but was not suitable for purifying T. gondii tissue cysts produced in vitro. The IMS described here should favor proteomic studies involving tissue cysts of T. gondii.

7.
Mol Microbiol ; 118(6): 601-622, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36210525

RESUMO

Virulence and persistence of the obligate intracellular parasite Toxoplasma gondii involve the secretion of effector proteins belonging to the family of dense granule proteins (GRAs) that act notably as modulators of the host defense mechanisms and participate in cyst wall formation. The subset of GRAs residing in the parasitophorous vacuole (PV) or exported into the host cell, undergo proteolytic cleavage in the Golgi upon the action of the aspartyl protease 5 (ASP5). In tachyzoites, ASP5 substrates play central roles in the morphology of the PV and the export of effectors across the translocon complex MYR1/2/3. Here, we used N-terminal amine isotopic labeling of substrates to identify novel ASP5 cleavage products by comparing the N-terminome of wild-type and Δasp5 lines in tachyzoites and bradyzoites. Validated substrates reside within the PV or PVM in an ASP5-dependent manner. Remarkably, Δasp5 bradyzoites are impaired in the formation of the cyst wall in vitro and exhibit a considerably reduced cyst burden in chronically infected animals. More specifically two-photon serial tomography of infected mouse brains revealed a comparatively reduced number and size of the cysts throughout the establishment of persistence in the absence of ASP5.


Assuntos
Ácido Aspártico Proteases , Toxoplasma , Animais , Camundongos , Toxoplasma/metabolismo , Ácido Aspártico Proteases/metabolismo , Proteínas de Protozoários/metabolismo , Infecção Persistente , Vacúolos/metabolismo , Ácido Aspártico Endopeptidases/metabolismo
8.
Eur J Protistol ; 86: 125922, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36155308

RESUMO

Resting cysts protect ciliates against adverse environmental conditions. The morphology and ultrastructure of resting cysts has been described in very few Oligotrichea, a group of mainly marine planktonic ciliates. The present study provides the first ultrastructural data for loricate choreotrichids, applying light and electron microscopy on the cysts of the tintinnid Schmidingerella meunieri (Kofoid and Campbell, 1929) Agatha and Strüder-Kypke, 2012. The morphology of live cysts and the wall ultrastructure of cryofixed cysts were morphometrically analysed. The resting cyst is roughly flask-shaped, broadening to a slightly concave, laterally protruding anterior plate. An emergence pore closed by a skull cap-shaped papula is directed to the bottom of the lorica on the opposite side of the cyst. The cyst wall consists of an ectocyst, mesocyst, and endocyst differing in thickness, structure, and nitrogen concentration as revealed by conventional transmission electron microscopy, electron energy loss spectroscopy, and electron spectroscopic imaging. The cysts of S. meunieri belong to the kinetosome-resorbing type, which also occurs in the majority of hypotrich ciliates. Two main features (flask-shape and presence of an emergence pore) are shared with the closely related aloricate choreotrichids and oligotrichids, distinguishing the Oligotrichea from the hypotrich and the more distantly related euplotid ciliates.


Assuntos
Alveolados , Cilióforos , Filogenia , Cilióforos/ultraestrutura , Microscopia Eletrônica de Transmissão
9.
Acta Trop ; 232: 106514, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35580637

RESUMO

Toxoplasma gondii poses a major threat to economies and public health, and there are still no available vaccines for human against T. gondii infection. T. gondii cyst wall 2 (TgCST2, also known as dense granule protein-47) is a critical molecule in the establishment of chronic infection, making it a potential vaccine candidate. In this research, the recombinant TgCST2 (rTgCST2) was employed to evaluate the protective efficacy of TgCST2 antigen using BALB/c mice model against T. gondii infections via active immunization trials. First, the strong immunogenicity of TgCST2 was indicated by immunoblotting and immunofluorescence, which mean that TgCST2 might elicit robust immune responses in the organism. Then, after triply subcutaneous immunization with rTgCST2/ISA 201 emulsion, high levels of Toxoplasma-specific IgG, IgG1, IgG2a and cytokines (Interferon γ and interleukin 10) further suggested that TgCST2 was a promising immunogenic antigen. More importantly, this antigen could prolong survival in RH strain infected mice and resulted in the lower brain cysts size and number of PRU strain infected mice. These preliminary results demonstrated the immunoprophylactic effects of TgCST2 antigen and will inform new studies in developing subunit recombinant vaccines against T. gondii.


Assuntos
Vacinas Protozoárias , Toxoplasma , Toxoplasmose Animal , Vacinas de DNA , Animais , Anticorpos Antiprotozoários , Citocinas/metabolismo , Imunoglobulina G , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Protozoários/genética , Vacinas Protozoárias/genética , Proteínas Recombinantes/genética , Toxoplasmose Animal/prevenção & controle
10.
Surg Neurol Int ; 13: 102, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399892

RESUMO

Background: Glioependymal cysts (GECs) are rare, benign congenital intracranial cysts that account for 1% of all intracranial cysts. Surgical interventions are required for patients with symptomatic GECs. However, the optimal treatment remains controversial, especially in infants. Here, we report a male infant case of GECs that successfully underwent minimally invasive combined neuroendoscopic cyst wall fenestration and cyst-peritoneal (CP) shunt. Case Description: The boy was delivered transvaginally at 38 weeks and 6 days of gestation with no neurological deficits. Magnetic resonance imaging (MRI) at birth revealed multiple cysts with smooth and rounded borders and a non-enhancing wall in the right parieto-occipital region. The size of the cyst had increased rapidly compared to that of the prenatal MRI, which was performed at 37 weeks and 2 days. On the day of birth, Ommaya cerebrospinal fluid (CSF) reservoir was placed into the largest outer cyst. The patient underwent intermittent CSF drainage; however, he experienced occasional vomiting. At 2 months, he underwent combined neuroendoscopic cyst wall fenestration and CP shunt through a small hole. The patient's postoperative course was uneventful and there was no recurrence of the cyst. The pathological diagnosis was GEC. Conclusion: Combined neuroendoscopic cyst wall fenestration and CP shunt are a minimally invasive and effective treatment for infants with GECs.

11.
FEBS Lett ; 596(1): 112-127, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34820838

RESUMO

Zinc ribbons, one of the largest fold groups among zinc fingers, often include proteins involved in the transcription machinery. Here, we identify and characterize one such zinc ribbon-bearing protein in the apicomplexan parasite Toxoplasma gondii, annotated as putative transcription elongation factor 1 (ELF1), with predicted functions in transcription and chromatin maintenance. We show that this ELF1 homolog, referred to as T. gondii ELF1-like divergent (TgELD), is expressed in both tachyzoite and bradyzoite developmental stages. TgELD associates with the cytoskeleton in the tachyzoites, while it transiently becomes a part of the cyst wall in the early bradyzoites, followed by a cytosolic and peripheral localization in late bradyzoites. TgELD is phosphorylated by a casein kinase 2-like protein, which has potential implications for its localization and function in the parasite.


Assuntos
Toxoplasma
12.
IDCases ; 27: e01359, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34917473

RESUMO

Echinococcosis is a re-emerging public health issue in developing countries as most communities are homes to dogs and other domesticated animals while cattle raising is a major habit of most sub-Saharan countries. The usual presentations include liver and lung cysts. While few documentations and publications have been made on extra-pulmonary intrathoracic hydatid cysts in other parts of the world, there has been no published document on extra-pulmonary intrathoracic hydatid cysts consisting of eighty or more cystic masses in a single patient in Ethiopia. We present a case of right sided extra-pulmonary intrathoracic hydatid cysts in a 20-year old Ethiopian male patient with compressive respiratory symptoms and significant social history of cohabiting with dogs throughout childhood. The patient was treated by surgery via a posterolateral thoracotomy and had a smooth Post-operative course and discharged home on postoperative day 15 on albendazole and analgesics. Intraoperative findings included approximately 1500 ml of cystic fluid, eighty cystic masses and collapsed lung.

13.
Front Neurol ; 12: 701177, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630280

RESUMO

Objective: Rathke cleft cysts (RCC) are benign sellar lesions, and endoscopic endonasal surgery (EES) for symptomatic RCC is becoming increasingly popular, but total resection or partial resection (TR or PR) of the cyst wall is still inconclusive. The aim of this study was to review the complications and clinical prognoses associated with total and partial resection of the cyst wall by EES. Methods: We retrospectively analyzed a series of 72 patients with symptomatic RCC treated by EES from -January 2011 to June 2019 at Shenzhen University First Affiliated Hospital. For these 72 cases, 30 were treated with TR and 42 were treated with PR. Intra- and post-operative complications and clinical prognosis were investigated. Results: All 72 patients underwent a pure EES. In the TR group, 10 patients (33.3%) had intraoperative cerebrospinal fluid leakage (CSF leak), three patients (10%) had postoperative CSF leak, eight patients (26.7%) had postoperative diabetes insipidus (DI), eight patients (26.7%) had postoperative electrolyte disturbance, and 12 patients (40%) had temporary hypopituitarism postoperatively. While in the PR group, three patients (7.1%) had intraoperative CSF leak, two patients (4.8%) had postoperative DI, three patients (7.1%) had postoperative electrolyte disturbance, four patients (9.5%) had temporary hypopituitarism postoperatively, and no cases experienced postoperative CSF leak. The intra- and post-operative complications were significantly higher in TR group then PR group (P IntraoperativeCSFleak = 0.004, P Post-operativeCSFleak =0.036, P TransientDI = 0.008, P Temporaryhypopituitarism = 0.002, P Permanenthypopituitarism = 0.036, P Electrolytedisturbance = 0.023). No significant differences in post-operative improvement and recurrence. Conclusions: EES is a safe and effective approach for the treatment of symptomatic RCC. Complete sucking out the cyst contents and partial resection of the cyst wall may be sufficient for treatment, and total resection of the cyst wall is associated with a higher incidence of complications.

14.
Zhonghua Zhong Liu Za Zhi ; 43(9): 973-978, 2021 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-34530582

RESUMO

Objective: To investigate the reoperation and perioperative management of residual cyst wall with perineal intractable sinus after resection of presacral cyst tumors. Methods: The clinical data of 29 patients with residual cyst wall and perineal intractable sinus after resection of presacral cyst tumors in Affiliated Cancer Hospital of Zhengzhou University from January 2014 to August 2019 were reviewed, including the characteristics of the residual cyst wall with perineal intractable sinus after resection of presacral cyst tumors, surgical method, and perioperative management. Results: Twenty-nine patients with residual cyst wall and perineal intractable sinus after resection of presacral cyst tumors, including 9 cases of epidermoid cysts, 7 cases of dermoid cysts, 10 cases of mature teratomas and 3 cases of malignant cysts (including malignant transformation of caudate cyst and teratoma); The 29 patients underwent posterior approaches for cyst resection in other hospital before, of whom 1 patient underwent posterior combined with transabdominal approach. All of thes patients underwent resection of residual presacral cyst wall and perineal intractable sinus in our hospital, of whom 25 patients underwent a transperineal approach through an arc-shaped incision anterior to the apex of the coccyx, and the other 4 patients underwent transperineal arc-shaped incision combined with transabdominal approach. All of the patients were cured without serious complications occurring, postoperative pathological and the magnetic resonance imaging diagnosis showed that the residual cyst wall and perineal intractable sinus were all completely removed. Conclusion: Appropriate surgical approache and perioperative treatment for the patients with residual cyst wall and perineal intractable sinus are very important to promote the resection of residual cyst wall and the healing of perineal intractable sinus.


Assuntos
Cistos , Teratoma , Humanos , Imageamento por Ressonância Magnética , Reoperação , Teratoma/diagnóstico por imagem , Teratoma/cirurgia
15.
Orthop Surg ; 13(4): 1159-1169, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33942543

RESUMO

OBJECTIVE: To compare the clinical efficacy and safety of arthroscopic internal drainage for the treatment of unicameral popliteal cysts with or without cyst wall resection. METHODS: This was a retrospective case-control study of 73 patients diagnosed with unicameral popliteal cysts from January 2012 to January 2019 who received arthroscopic treatment. The study included 38 cases with cyst wall resection (CWR group) and 35 cases with cyst wall preservation (CWP group). The CWR group consisted of 14 men and 24 women with an average age of 51.8 years, while the CWP group consisted of 13 men and 22 women with an average age of 52.0 years. All patients were examined for intra-articular lesions and communicating ports by magnetic resonance imaging (MRI) prior to surgery, and recurrence of cysts was evaluated at the last follow-up examination. Rauschning and Lindgren grade (R-L grade) and Lysholm score were used to evaluate clinical outcomes. In addition, operation time and complications were recorded. RESULTS: The average length of follow-up was 24.2 months (range, 16 to 32 months). There were no considerable differences in age, gender, cyst size, Lysholm score, R-L grade and concomitant intra-articular cases between the CWR group and CWP group prior to surgery (P > 0.05). The last follow-up MRI scans showed that in the CWR group, the cyst disappeared in 25 cases and shrunk in 13 cases. In the CWP group, the cyst disappeared in 22 cases, shrunk in 12 cases and persisted in one case. There was no obvious difference in recurrence rate between the two groups (0% vs 2.9%, P = 0.899). At the last follow-up, there were no differences in the R-L grade (P = 0.630) and Lysholm score (88.3 ± 5.6 points vs 90.1 ± 3.8 points, P = 0.071) between the two groups. Compared with the CWP group, operation time was significantly prolonged in the CWR group (38.3 ± 3.1 min vs 58.3 ± 4.4 min, P < 0.05). In the CWR group, three cases occurred fluid infiltration under the gastrocnemius muscle, which improved after pressure bandaging and cold compress. In another three cases, hematoma was found. The incidence of complications in the CWR group was markedly higher than that in the CWP group (15.8% vs 0%, P < 0.05). During the follow-up period, none of the patients developed serious complications such as neurovascular injury, deep venous thrombosis, or infection. CONCLUSION: For unicameral popliteal cysts, arthroscopic internal drainage combined with resection of the cyst wall did not further improve the clinical outcomes or reduce the recurrence rate, while prolonging the operation time and increasing the possibility of complications.


Assuntos
Artroscopia/métodos , Drenagem/métodos , Procedimentos de Cirurgia Plástica/métodos , Cisto Popliteal/cirurgia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários
16.
mSphere ; 6(2)2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33883265

RESUMO

Toxoplasma gondii causes a chronic infection that renders the immunocompromised human host susceptible to toxoplasmic encephalitis triggered by cyst reactivation in the central nervous system. The dense granule protein GRA12 is a major parasite virulence factor required for parasite survival during acute infection. Here, we characterized the role of four GRA12-related genes in acute and chronic stages of infection. While GRA12A, GRA12B, and GRA12D were highly expressed in asexual stage tachyzoites and bradyzoites, expression of GRA12C appeared to be restricted to the sexual stages. In contrast to deletion of GRA12 (Δgra12), no major defects in acute virulence were observed in Δgra12A, Δgra12B, or Δgra12D parasites, though Δgra12B parasites exhibited an increased tachyzoite replication rate. Bradyzoites secreted GRA12A, GRA12B, and GRA12D and incorporated these molecules into the developing cyst wall, as well as the cyst matrix in distinct patterns. Similar to GRA12, GRA12A, GRA12B, and GRA12D colocalized with the dense granules in extracellular tachyzoites, with GRA2 and the intravacuolar network in the tachyzoite stage parasitophorous vacuole and with GRA2 in the cyst matrix and cyst wall. Chronic stage cyst burdens were decreased in mice infected with Δgra12A parasites and were increased in mice infected with Δgra12B parasites. However, Δgra12B cysts were not efficiently maintained in vivo Δgra12A, Δgra12B, and Δgra12D in vitro cysts displayed a reduced reactivation efficiency, and reactivation of Δgra12A cysts was delayed. Collectively, our results suggest that a family of genes related to GRA12 play significant roles in the formation, maintenance, and reactivation of chronic stage cysts.IMPORTANCE If host immunity weakens, Toxoplasma gondii cysts recrudesce in the central nervous system and cause a severe toxoplasmic encephalitis. Current therapies target acute stage infection but do not eliminate chronic cysts. Parasite molecules that mediate the development and persistence of chronic infection are poorly characterized. Dense granule (GRA) proteins such as GRA12 are key virulence factors during acute infection. Here, we investigated four GRA12-related genes. GRA12-related genes were not major virulence factors during acute infection. Instead, GRA12-related proteins localized at the cyst wall and cyst matrix and played significant roles in cyst development, persistence, and reactivation during chronic infection. Similar to GRA12, the GRA12-related proteins selectively associated with the intravacuolar network of membranes inside the vacuole. Collectively, our results support the hypothesis that GRA12 proteins associated with the intravacuolar membrane system support parasite virulence during acute infection and cyst development, persistence, and reactivation during chronic infection.


Assuntos
Antígenos de Protozoários/genética , Regulação da Expressão Gênica , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Toxoplasma/genética , Vacúolos/metabolismo , Animais , Antígenos de Protozoários/metabolismo , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Vacúolos/parasitologia , Fatores de Virulência
17.
World Neurosurg ; 149: 190-194, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33677088

RESUMO

OBJECTIVE: The purpose of this paper is to describe the variation of surgical plan and technique required in a rare subset of hemangioblastomas compared with the accepted general strategy. The established rule in hemangioblastoma surgery is to avoid cyst wall removal, as it is not neoplastic, and it will not recur if mural nodule is completely removed. However, the wall of the associated cyst is occasionally enhanced by gadolinium on preoperative magnetic resonance imaging. METHODS: We present the case of a patient with a hemangioblastoma that was progressively compressed by a growing cyst, with the final appearance of a contrast-enhanced cyst wall. We collected similar cases reported in the literature. RESULTS: Our study points out the need for a tailored preoperative strategy, the usefulness of intraoperative fluorescent dyes, and the crucial role of frozen section histopathologic analysis to confirm diagnosis and optimize treatment. CONCLUSIONS: When a hemangioblastoma is associated with a contrast-enhanced cyst, care must be taken to intraoperatively confirm the presence of neoplastic cells and eventually remove the neoplastic cyst wall to reduce the risk of recurrence.


Assuntos
Neoplasias Cerebelares/cirurgia , Meios de Contraste , Cistos/cirurgia , Hemangioblastoma/cirurgia , Imageamento por Ressonância Magnética/métodos , Adolescente , Neoplasias Cerebelares/complicações , Neoplasias Cerebelares/diagnóstico por imagem , Cistos/complicações , Cistos/diagnóstico por imagem , Feminino , Hemangioblastoma/complicações , Hemangioblastoma/diagnóstico por imagem , Humanos
18.
IJU Case Rep ; 4(1): 18-21, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33426489

RESUMO

INTRODUCTION: Renal tumors are often associated with renal cysts. Meanwhile, in some cases there are challenging issues of how to diagnose renal cystic tumors and to decide surgical procedures. CASE PRESENTATION: A 75-year-old man was referred to our department for a 21-mm tumor by his left kidney. Contrast-enhanced computed tomography showed an intense contrast uptake the tumor, which was adjacent to a 64-mm unilocular renal cyst with no contrasting effects. It was clinically diagnosed as renal cell carcinoma, stage T1aN0M0, and treated with robot-assisted partial nephrectomy, for both the solid tumor and the adjacent cyst. Pathological findings revealed a tumor cell clump within the cyst wall, concurrent with the renal cell carcinoma. The patient has remained free of disease at 1 year after surgery. CONCLUSION: A partial nephrectomy that includes the entire cyst wall should be considered for renal tumor associated with unilocular renal cyst.

19.
Microb Pathog ; 152: 104643, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33232762

RESUMO

Toxoplasma gondii differentiation from proliferating tachyzoites into latent bradyzoites is central to pathogenesis and transmission. Strong humoral immune response has been reported against tachyzoite antigens, however, antibody-mediated response towards bradyzoite antigens is poorly characterized. This work aimed to study the humoral immune response towards bradyzoite and associated cyst wall antigens particularly CST1. The immunoreactivity of 404 goats, 88 sheep and 92 human sera to recombinant (CST1 and SRS9) and native proteins of encysted bradyzoite along with well-established tachyzoite antigens (SAG1 and GRA7) was determined using ELISA, Western blot and immunofluorescence analysis (IFA). ELISA results revealed nearly 50% of sera contain T. gondii specific antibodies. Results were further validated using Western blot and IFA. T. gondii positive sera predominantly recognized the cyst wall besides the known tachyzoite surface antigens. The presence of CST1 antibodies in seropositive samples were in line with the staining patterns which were consistent with CST localization. Notably, T. gondii IgM- IgG+ sera recognize the cyst wall whereas IgM + IgG-sera recognize tachyzoite antigens indicating acute infection consistent with presence of parasite DNA. The study demonstrates a strong humoral response against bradyzoite associated cyst wall antigens across naturally infected animals and humans. CST1 emerged as a key immunomodulatory antigen which may have direct implications for clinical immunodiagnostics.


Assuntos
Imunidade Humoral , Toxoplasma , Toxoplasmose , Animais , Antígenos de Protozoários/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Proteínas de Protozoários , Ovinos , Toxoplasmose/imunologia
20.
BMC Musculoskelet Disord ; 21(1): 440, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631287

RESUMO

BACKGROUND: This study aimed to compare the arthroscopic internal drainage of popliteal cysts alone or in combination with cyst wall resection in terms of clinical outcomes. METHODS: Forty-two consecutive patients with symptomatic popliteal cysts received arthroscopic treatment. Specifically, 20 of them received arthroscopic internal drainage (AI group) alone and 22 received arthroscopic internal drainage combined with cyst wall resection (AICR group) through double posteromedial portals. Magnetic resonance imaging (MRI) was performed to identify recurrence of popliteal cysts. The Lysholm score and Rauschning-Lindgren grade were used to assess the clinical outcomes. The median of the follow-up period was 24 months (12-48 months). RESULTS: The two groups (AI group and AICR group) were similar in age, gender, cyst diameter, associated joint disorder, preoperative Lysholm score, preoperative Rauschning-Lindgren grade and follow-up period (P > 0.05). Relative to the AI group, the AICR group had a significantly prolonged operation time (P < 0.05) and a higher incidence of complications (P < 0.05). In both groups, the Rauschning-Lindgren grade at the last follow-up significantly differed from the preoperative grade (P < 0.05) and the Lysholm knee score remarkably increased compared to the preoperative score (P < 0.05); however, there were no differences between the two groups at the last follow-up (P > 0.05). According to the MRI results, the cyst disappeared in 11 (55%), shrank in size in 6 (30%) and existed in 3 (15%) patients in the AI group, and was absent in 18 (81.8%) and shrank in size in 4 (18.2%) patients in the AICR group, suggesting a significant difference between the two (P < 0.05). CONCLUSION: Additional resection of cyst wall can result in a lower recurrence rate of cysts but extend the operation time and increase the incidence of perioperative complications compared with arthroscopic internal drainage of popliteal cysts alone.


Assuntos
Artroscopia/métodos , Drenagem/métodos , Recidiva Local de Neoplasia/prevenção & controle , Cisto Popliteal/cirurgia , Adulto , China , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Cisto Popliteal/diagnóstico por imagem , Complicações Pós-Operatórias , Índice de Gravidade de Doença , Resultado do Tratamento
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