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1.
Ochsner J ; 23(4): 332-342, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38143542

RESUMO

Background: Spinal arachnoid cysts are rarely occurring benign cerebrospinal fluid-containing lesions that can occur anywhere along the spinal axis but are principally seen in the thoracic spine. They occur either ventrally or dorsally and can be extradural, intradural extramedullary, or intramedullary. They may be asymptomatic or can present with insidious pain and neurologic symptoms related to spinal cord and/or nerve root compression. Case Report: A 49-year-old male developed sudden midback pain with rapid progression to gait instability, urinary retention, and paraplegia within 10 hours. His presentation for neurosurgical care was delayed because of lack of funds and unfavorable insurance policies. At presentation 3 months after the onset of symptoms, magnetic resonance imaging of his spine showed a ventrolateral intradural extramedullary cystic lesion at T5-T6 with severe cord compression. He underwent T5-T6 and T6-T7 laminectomies with a limited left sixth rib costotransversectomy for microsurgical resection of the cyst. Postoperatively, the patient reported improvement in bladder and bowel control, but his paraplegia persisted. Conclusion: Arachnoid cysts are mostly benign lesions; however, they may have disastrous outcomes if not promptly addressed with the necessary urgency when symptoms are progressive, as in our patient.

2.
Dev Comp Immunol ; 147: 104894, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37467826

RESUMO

B-cell cloning methods enable the analysis of antibody responses against target antigens and can be used to reveal the host antibody repertoire, antigenic sites (epitopes), and details of protective immunity against pathogens. Here, we describe improved methods for isolation of canine peripheral blood B cells producing antibodies against canine parvovirus (CPV) capsids by fluorescence-activated cell sorting, followed by cell cloning. We cultured sorted B cells from an immunized dog in vitro and screened for CPV-specific antibody production. Updated canine-specific primer sets were used to amplify and clone the heavy and light chain immunoglobulin sequences directly from the B cells by reverse transcription and PCR. Monoclonal canine IgGs were produced by cloning heavy and light chain sequences into antibody expression vectors, which were screened for CPV binding. Three different canine monoclonal antibodies were analyzed, including two that shared the same heavy chain, and one that had distinct heavy and light chains. The antibodies showed broad binding to CPV variants, and epitopes were mapped to antigenic sites on the capsid. The methods described here are applicable for the isolation of canine B cells and monoclonal antibodies against many antigens.


Assuntos
Infecções por Parvoviridae , Parvovirus Canino , Parvovirus , Cães , Animais , Anticorpos Antivirais , Parvovirus Canino/genética , Anticorpos Monoclonais , Epitopos , Clonagem Molecular , Infecções por Parvoviridae/veterinária
3.
J Virol ; 97(7): e0016123, 2023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37367301

RESUMO

Parvoviruses are among the smallest and superficially simplest animal viruses, infecting a broad range of hosts, including humans, and causing some deadly infections. In 1990, the first atomic structure of the canine parvovirus (CPV) capsid revealed a 26-nm-diameter T=1 particle made up of two or three versions of a single protein, and packaging about 5,100 nucleotides of single-stranded DNA. Our structural and functional understanding of parvovirus capsids and their ligands has increased as imaging and molecular techniques have advanced, and capsid structures for most groups within the Parvoviridae family have now been determined. Despite those advances, significant questions remain unanswered about the functioning of those viral capsids and their roles in release, transmission, or cellular infection. In addition, the interactions of capsids with host receptors, antibodies, or other biological components are also still incompletely understood. The parvovirus capsid's apparent simplicity likely conceals important functions carried out by small, transient, or asymmetric structures. Here, we highlight some remaining open questions that may need to be answered to provide a more thorough understanding of how these viruses carry out their various functions. The many different members of the family Parvoviridae share a capsid architecture, and while many functions are likely similar, others may differ in detail. Many of those parvoviruses have not been experimentally examined in detail (or at all in some cases), so we, therefore, focus this minireview on the widely studied protoparvoviruses, as well as the most thoroughly investigated examples of adeno-associated viruses.


Assuntos
Parvoviridae , Animais , Humanos , Capsídeo/ultraestrutura , Proteínas do Capsídeo/química , Proteínas do Capsídeo/metabolismo , DNA Viral/metabolismo , Parvoviridae/genética , Parvoviridae/ultraestrutura , Infecções por Parvoviridae/metabolismo , Infecções por Parvoviridae/virologia , Dependovirus/genética , Dependovirus/metabolismo , Dependovirus/ultraestrutura
4.
J Virol ; 97(6): e0009023, 2023 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-37199627

RESUMO

Canine parvovirus (CPV) is a small nonenveloped single-stranded DNA virus that causes serious diseases in dogs worldwide. The original strain of the virus (CPV-2) emerged in dogs during the late 1970s due to a host range switch of a virus similar to the feline panleukopenia virus that infected another host. The virus that emerged in dogs had altered capsid receptor and antibody binding sites, with some changes affecting both functions. Further receptor and antibody binding changes arose when the virus became better adapted to dogs or to other hosts. Here, we used in vitro selection and deep sequencing to reveal how two antibodies with known interactions select for escape mutations in CPV. The antibodies bound two distinct epitopes, and one largely overlapped the host receptor binding site. We also generated mutated antibody variants with altered binding structures. Viruses were passaged with wild-type (WT) or mutated antibodies, and their genomes were deep sequenced during the selective process. A small number of mutations were detected only within the capsid protein gene during the first few passages of selection, and most sites remained polymorphic or were slow to go to fixation. Mutations arose both within and outside the antibody binding footprints on the capsids, and all avoided the transferrin receptor type 1 binding footprint. Many selected mutations matched those that have arisen in the natural evolution of the virus. The patterns observed reveal the mechanisms by which these variants have been selected in nature and provide a better understanding of the interactions between antibody and receptor selections. IMPORTANCE Antibodies protect animals against infection by many different viruses and other pathogens, and we are gaining new information about the epitopes that induce antibody responses against viruses and the structures of the bound antibodies. However, less is known about the processes of antibody selection and antigenic escape and the constraints that apply in this system. Here, we used an in vitro model system and deep genome sequencing to reveal the mutations that arose in the virus genome during selection by each of two monoclonal antibodies or their mutated variants. High-resolution structures of each of the Fab:capsid complexes revealed their binding interactions. The wild-type antibodies or their mutated variants allowed us to examine how changes in antibody structure influence the mutational selection patterns seen in the virus. The results shed light on the processes of antibody binding, neutralization escape, and receptor binding, and they likely have parallels for many other viruses.


Assuntos
Anticorpos Antivirais , Sítios de Ligação de Anticorpos , Capsídeo , Parvovirus Canino , Animais , Cães , Capsídeo/metabolismo , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Epitopos/genética , Epitopos/análise , Parvovirus Canino/genética , Parvovirus Canino/metabolismo , Mutação , Anticorpos Antivirais/genética , Anticorpos Antivirais/metabolismo , Sítios de Ligação de Anticorpos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Antígenos Virais/metabolismo , Seleção Genética
5.
bioRxiv ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36711712

RESUMO

Canine parvovirus (CPV) is a small non-enveloped single-stranded DNA virus that causes serious diseases in dogs worldwide. The original strain of the virus (CPV-2) emerged in dogs during the late-1970s due to a host range switch of a virus similar to the feline panleukopenia virus (FPV) that infected another host. The virus that emerged in dogs had altered capsid receptor- and antibody-binding sites, with some changes affecting both functions. Further receptor and antibody binding changes arose when the virus became better adapted to dogs or to other hosts. Here, we use in vitro selection and deep sequencing to reveal how two antibodies with known interactions select for escape mutations in CPV. The antibodies bind two distinct epitopes, and one largely overlaps the host receptor binding site. We also engineered antibody variants with altered binding structures. Viruses were passaged with the wild type or mutated antibodies, and their genomes deep sequenced during the selective process. A small number of mutations were detected only within the capsid protein gene during the first few passages of selection, and most sites remained polymorphic or were slow to go to fixation. Mutations arose both within and outside the antibody binding footprints on the capsids, and all avoided the TfR-binding footprint. Many selected mutations matched those that have arisen in the natural evolution of the virus. The patterns observed reveal the mechanisms by which these variants have been selected in nature and provide a better understanding of the interactions between antibody and receptor selections. IMPORTANCE: Antibodies protect animals against infection by many different viruses and other pathogens, and we are gaining new information about the epitopes that induce antibody responses against viruses and the structures of the bound antibodies. However, less is known about the processes of antibody selection and antigenic escape and the constraints that apply in this system. Here, we use an in vitro model system and deep genome sequencing to reveal the mutations that arise in the virus genome during selection by each of two monoclonal antibodies or their engineered variants. High-resolution structures of each of the Fab: capsid complexes revealed their binding interactions. The engineered forms of the wild-type antibodies or mutant forms allowed us to examine how changes in antibody structure influence the mutational selection patterns seen in the virus. The results shed light on the processes of antibody binding, neutralization escape, and receptor binding, and likely have parallels for many other viruses.

6.
Clin Neurol Neurosurg ; 179: 35-41, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30818126

RESUMO

OBJECTIVES: A general consensus based on a multidisciplinary perspective involving an international panel was recently developed for management of patients with idiopathic intracranial hypertension (IIH). In this paper, the authors sought to develop further on the aspect of this consensus that concerns monitoring progression of the disease. PATIENTS AND METHODS: A systematic literature review of previous publications on monitoring disease progression in IIH and a meta-analysis to examine efficacy of method of monitoring employed in each study. The authors present a brief descriptive analysis of challenges with monitoring progression of the disease and propose a risk stratification to aid monitoring. RESULTS: Of a total of 382 publications identified from the literature search, only 8 studies (144 patients) satisfied inclusion criteria and were included for analysis. Among these, 3 were based on ICP monitoring while the remaining 5 focused on ophthamological evaluation. Interestingly, there were neither any studies on monitoring with progression of clinical features nor any study on monitoring with symptomatology associated with IIH among the selected studies. CONCLUSION: There is a paucity of studies in the literature on methods of monitoring disease progression in IIH. Though close attention to adequate evaluation and proper care of patients with IIH remains the key in managing this problem, this proposed risk stratification will be an objective tool and useful guide to better monitor these patients according to their extent of risk from the disease and possibly for planning treatment and intervention.


Assuntos
Hipertensão Intracraniana/complicações , Cegueira/epidemiologia , Cegueira/etiologia , Progressão da Doença , Humanos , Hipertensão Intracraniana/diagnóstico , Monitorização Fisiológica , Medição de Risco
7.
Lett Appl Microbiol ; 67(4): 354-362, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29947432

RESUMO

Analysis of the bacterial community dynamics during the production of traditional fermented condiments is important for food safety assessment, quality control and development of starter culture technology. In this study, bacteria isolated during the processing of iru and ogiri, two commonly consumed condiments in Nigeria, were characterized based on phylogenetic analyses of the bacterial 16S rRNA gene. A total of 227 isolates were obtained and clustered into 12 operational taxonomic units (OTUs) based on 97% 16S rRNA gene similarity. The OTUs spanned three phyla (Firmicutes, Actinobacteria and Proteobacteria), and nine genera: Acinetobacter, Aerococcus, Bacillus, Enterococcus, Enterobacter, Lysinibacillus, Micrococcus, Proteus and Staphylococcus. OTUs closely related to species of Bacillus dominated the processing stages of both condiments. Although no single OTU occurred throughout iru processing stages, an OTU (mostly related to B. safensis) dominated the ogiri processing stages indicating potentials for the development of starter culture. However, other isolates such as those of Enterococcus spp. and Lysinibacillus spp. may be potential starters for iru fermentation. Presumptive food-borne pathogens were also detected at some stages of the condiments' processing, possibly due to poor hygienic practices. SIGNIFICANCE AND IMPACT OF THE STUDY: Iru and ogiri are important condiments used for flavour enhancement in foods and serve as protein substitutes in diets among rural populations across West Africa. Consumption of these condiments is growing, reinforcing the need to scale up their production. Production of these condiments includes spontaneous fermentation, which often leads to inconsistent product quality and unguaranteed safety. This study has demonstrated the bacterial succession in iru and ogiri processing and highlights species that could be selected and exploited for starter culture development. This study provides a starting point to produce quality and microbiologically safe iru and ogiri condiments.


Assuntos
Actinobacteria/metabolismo , Condimentos/microbiologia , Alimentos Fermentados/microbiologia , Firmicutes/metabolismo , Proteobactérias/metabolismo , Actinobacteria/classificação , Actinobacteria/genética , Bacillus/classificação , Bacillus/genética , Bacillus/metabolismo , Fermentação , Firmicutes/classificação , Firmicutes/genética , Inocuidade dos Alimentos , Nigéria , Filogenia , Proteobactérias/classificação , Proteobactérias/genética , RNA Ribossômico 16S/genética , Sementes/metabolismo
9.
Childs Nerv Syst ; 34(2): 311-319, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29026989

RESUMO

PURPOSE: Spina bifida is a common congenital anomaly of the nervous system. It is frequently associated with significant morbidity and sometimes mortality in affected children. In this paper, we review the clinico-epidemiological pattern, peculiarities, and therapeutic challenges of this condition in our practice setting. METHODS: This is a retrospective study of all cases of spina bifida managed from July 2000 to March 2016 at a tertiary health facility located in the southwest region of Nigeria. Relevant information was retrieved from the medical records. The data was collected using a pro forma and analyzed with SPSS version 22. RESULTS: Data from 148 patients was reviewed and analyzed. There were 78 males and 70 females. Only 5.8% of these children were delivered at the health institution. A fifth (20%) of the patients were first born of their mothers. The mean maternal age was 29 years. Few (10.1%) mothers use folate medication prior to conception and only 58% of the mothers use folate during antenatal care. Mean duration of pregnancy was 38 weeks. The most common anatomical site was lumbosacral region (74.3%) while the most common pathology was myelomeningocele 80.4%. Mean age at surgery was 88.68 h. Mean duration of surgery was 92.8 min. Mean follow-up duration was 46.8 weeks. As many as 59% of the patients had some neurologic improvement noticed during follow-up clinic visits. CONCLUSION: Spina bifida occurs frequently in our environment. Low socio-economic status and poor antenatal clinic visits contributes significantly to its occurrence.


Assuntos
Gerenciamento Clínico , Hospitais de Ensino/tendências , Disrafismo Espinal/epidemiologia , Disrafismo Espinal/cirurgia , Adulto , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Nigéria/epidemiologia , Estudos Retrospectivos , Disrafismo Espinal/diagnóstico
10.
Afr J Paediatr Surg ; 13(2): 76-81, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27251657

RESUMO

BACKGROUND: It has been generally observed that children achieve better convalescence in the home environment especially if discharged same day after surgery. This is probably due to the fact that children generally tend to feel more at ease in the home environment than in the hospital setting. Only few tertiary health institutions provide routine day-case surgery for paediatric neurosurgical patients in our sub-region. OBJECTIVE: To review the pattern and practice of paediatric neurosurgical day-cases at our hospital. PATIENTS AND METHODS: A prospective study of all paediatric day-case neurosurgeries carried out between June 2011 and June 2014. RESULTS: A total of 53 patients (34 males and 19 females) with age ranging from 2 days to 14 years were seen. Majority of the patients (77.4%) presented with congenital lesions, and the most common procedure carried out was spina bifida repair (32%) followed by ventriculoperitoneal shunt insertion (26.4%) for hydrocephalus. Sixty-eight percentage belonged to the American Society of Anesthesiologists physical status class 2, whereas the rest (32%) belonged to class 1. General anaesthesia was employed in 83% of cases. Parenteral paracetamol was used for intra-operative analgesia for most of the patients. Two patients had post-operative nausea and vomiting and were successfully managed. There was no case of emergency re-operation, unplanned admission, cancellation or mortality. CONCLUSION: Paediatric day-case neurosurgery is feasible in our environment. With careful patient selection and adequate pre-operative preparation, good outcome can be achieved.


Assuntos
Procedimentos Cirúrgicos Ambulatórios , Encefalopatias/cirurgia , Procedimentos Neurocirúrgicos , Adolescente , Encefalopatias/diagnóstico , Encefalopatias/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Nigéria , Padrões de Prática Médica , Estudos Prospectivos
11.
Mycotoxin Res ; 30(4): 207-11, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25033991

RESUMO

Aflatoxin M1 (AFM1) in milk from 100 different herds of free-grazing cows in Abeokuta, Nigeria, was analysed by immunoaffinity column cleanup and HPLC with fluorescence detection. AFM1 was found in 75% of the samples, the toxin levels in positive samples ranged from 9.0 to 456.0 ng/l. The mean AFM1 level in positive samples was 108.15 ng/l, exceeding, for example, the European Union maximum level by a factor of two. These results indicated that there is an urgent need to more closely control the milk of free-grazing cows for AFM1 in order to protect the health of humans consuming milk and milk products.


Assuntos
Aflatoxina M1/análise , Leite/química , Animais , Bovinos , Cromatografia de Afinidade , Cromatografia Líquida de Alta Pressão , Fluorometria , Nigéria
12.
J Health Popul Nutr ; 29(4): 415-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21957681

RESUMO

Five million children aged less than five years die annually due to diarrhoea. The aim of the study was to identify some possible contributing factors for persistent diarrhoea. Seven weaning foods, including a locally-made food, were evaluated by estimating the microbial load using the most probable number method and aflatoxin levels (AFM1, AFG1, AFG2, and AFB2) by immunoaffinity column extraction and high-performance liquid chromatography (HPLC) with detection of fluorescence. The results showed that the locally-made weaning food had the highest microbial count (2,000 cfu/g) and faecal streptococcal count (25 cfu/g). Moulds isolated were mainly Aspergillus niger, A. flavus, A. glaucus, Cladosporium sp., and Penicillium sp. The home-made weaning food recorded the highest fungal count (6,500 cfu/g). AFM1 of the weaning foods was 4.6-530 ng/mL. One weaning food had AFB1 level of 4,806 ng/g. Aflatoxin metabolites, apart from AFM1 and AFB1 present in the weaning foods, were AFG1 and AFG2. There were low microbial counts in commercial weaning foods but had high levels of aflatoxins (AFM1, AFG1, AFG2, AFB1, and AFB2). Growth and development of the infant is rapid, and it is, thus, possible that exposure to aflatoxins in weaning foods might have significant health effects.


Assuntos
Alimentos Infantis/microbiologia , Aflatoxinas/análise , Contaminação de Alimentos , Humanos , Lactente , Alimentos Infantis/análise , Fungos Mitospóricos/isolamento & purificação , Nigéria , Desmame
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