RESUMO
BACKGROUND: Autoantibodies, in particular those against aquaporin-4 and myelin-oligodendrocyte glycoprotein (MOG), aid as biomarkers in the differential diagnosis of demyelination. Here, we report on discovery of autoantibodies against flotillin in patients with multiple sclerosis (MS). METHODS: The target antigen was identified by histo-immunoprecipitation using the patients' sera and cryosections of rat or pig cerebellum combined with mass spectrometrical analysis. Correct identification was ascertained by indirect immunofluorescence and neutralization tests using the target antigens recombinantly expressed in HEK293 cells. RESULTS: Serum and CSF of the index patient produced a fine-granular IgG indirect immunofluorescence staining of the hippocampal and cerebellar molecular layers. Flotillin-1 and flotillin-2 were identified as target autoantigens. They also reacted with recombinant human flotillin-1/2 co-expressed in HEK293 cells, but not with the individual flotillins in fixed- and live-cell assays. Moreover, neutralization using flotillin-1/2, but not the single flotillins, abolished the tissue reactivity of patient serum. Screening of 521 patients, for whom anti-aquaporin-4 testing was requested and negative, revealed 8 additional patients with anti-flotillin-1/2 autoantibodies. All eight were negative for anti-MOG. Six patients ex post fulfilled the revised McDonald criteria for MS. Vice versa, screening of 538 MS sera revealed anti-flotillin-1/2 autoantibodies in eight patients. The autoantibodies were not found in a cohort of 67 patients with other neural autoantibody-associated syndromes and in 444 healthy blood donors. CONCLUSIONS: Autoantibodies against the flotillin-1/2 heterocomplex, a peripheral membrane protein that is involved in axon outgrowth and regeneration of the optic nerve, are present in 1-2% of patients with bona fide MS.
Assuntos
Autoanticorpos/metabolismo , Microdomínios da Membrana/metabolismo , Proteínas de Membrana/metabolismo , Esclerose Múltipla/metabolismo , Adulto , Animais , Autoanticorpos/imunologia , Feminino , Células HEK293 , Humanos , Masculino , Microdomínios da Membrana/imunologia , Proteínas de Membrana/imunologia , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Ratos , SuínosRESUMO
Employment status is related to treatment recovery and quality of life in breast cancer survivors, yet little is known about return to work in immigrant and minority survivors. We conducted an exploratory qualitative study using ethnically cohesive focus groups of urban breast cancer survivors who were African-American, African-Caribbean, Chinese, Filipina, Latina, or non-Latina white. We audio- and video-recorded, transcribed, and thematically coded the focus group discussions and we analyzed the coded transcripts within and across ethnic groups. Seven major themes emerged related to the participants' work experiences after diagnosis: normalcy, acceptance, identity, appearance, privacy, lack of flexibility at work, and employer support. Maintaining a sense of normalcy was cited as a benefit of working by survivors in each group. Acceptance of the cancer diagnosis was most common in the Chinese group and in participants who had a family history of breast cancer; those who described this attitude were likely to continue working throughout the treatment period. Appearance was important among all but the Chinese group and was related to privacy, which many thought was necessary to derive the benefit of normalcy at work. Employer support included schedule flexibility, medical confidentiality, and help maintaining a normal work environment, which was particularly important to our study sample. Overall, we found few differences between the different ethnic groups in our study. These results have important implications for the provision of support services to and clinical management of employed women with breast cancer, as well as for further large-scale research in disparities and employment outcomes.
Assuntos
Neoplasias da Mama/etnologia , Emigrantes e Imigrantes/psicologia , Emprego/psicologia , Grupos Minoritários/psicologia , Sobreviventes/psicologia , População Urbana , Adaptação Psicológica , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/psicologia , Emigrantes e Imigrantes/estatística & dados numéricos , Emprego/estatística & dados numéricos , Etnicidade/psicologia , Etnicidade/estatística & dados numéricos , Feminino , Grupos Focais , Humanos , Relações Interprofissionais , Pessoa de Meia-Idade , Grupos Minoritários/estatística & dados numéricos , Pesquisa Qualitativa , Sobreviventes/estatística & dados numéricos , População Urbana/estatística & dados numéricosRESUMO
BACKGROUND & AIMS: In contrast to the infection with other hepatotropic viruses, hepatitis A virus (HAV) always causes acute self-limited hepatitis, although the role for virus-specific CD8 T cells in viral containment is unclear. Herein, we analyzed the T cell response in patients with acute hepatitis by utilizing a set of overlapping peptides and predicted HLA-A2 binders from the polyprotein. METHODS: A set of 11 predicted peptides from the HAV polyprotein, identified as potential binders, were synthesized. Peripheral blood mononuclear cells (PBMCs) from patients were tested for IFNγ secretion after stimulation with these peptides and ex vivo with HLA-A2 tetramers. Phenotyping was carried out by staining with the activation marker CD38 and the memory marker CD127. RESULTS: Eight out of 11 predicted HLA-A2 binders showed a high binding affinity and five of them were recognized by CD8+ T cells from patients with hepatitis A. There were significant differences in the magnitude of the responses to these five peptides. One was reproducibly immunodominant and the only one detectable ex vivo by tetramer staining of CD8+ T cells. These cells have an activated phenotype (CD38hi CD127lo) during acute infection. Three additional epitopes were identified in HLA-A2 negative patients, most likely representing epitopes restricted by other HLA-class I-alleles (HLA-A11, B35, B40). CONCLUSIONS: Patients with acute hepatitis A have a strong multi-specific T cell response detected by ICS. With the tetramer carrying the dominant HLA-A2 epitope, HAV-specific and activated CD8+ T cells could be detected ex vivo. This first description of the HAV specific CTL-epitopes will allow future studies on strength, breadth, and kinetics of the T-cell response in hepatitis A.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Hepatite A/imunologia , Doença Aguda , Adolescente , Adulto , Idoso , Epitopos , Feminino , Antígeno HLA-A2/metabolismo , Vírus da Hepatite A/imunologia , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Legislação sobre Alimentos , Extratos Vegetais , Rotulagem de Produtos/legislação & jurisprudência , Árvores , Indústria Alimentícia , Geografia , Patentes como Assunto/legislação & jurisprudência , Extratos Vegetais/normas , Rotulagem de Produtos/normas , Sacarose , Estados Unidos , VermontRESUMO
The fsr locus of Enterococcus faecalis confers virulence in animal models. A retrospective analysis of fsr prevalence in diverse E. faecalis clinical isolates demonstrated fsr in all endocarditis isolates versus 53% of stool isolates (P = 0.005). This supports a role for fsr-mediated virulence in the pathogenesis of enterococcal infections in humans.
Assuntos
Enterococcus faecalis/genética , Enterococcus faecalis/patogenicidade , Genes Bacterianos , Infecções por Bactérias Gram-Positivas/microbiologia , Animais , Proteínas de Bactérias/genética , Sequência de Bases , DNA Bacteriano/genética , Endocardite Bacteriana/microbiologia , Humanos , Estudos Retrospectivos , Virulência/genéticaRESUMO
Little is known about the persistence of colonization with vancomycin-resistant Enterococcus faecium (VRE) in the nononcologic, non-intensive care unit patient. We studied all patients who had VRE isolated on > or =2 occasions of > 1 year apart (Study A) and those who had been "cleared" of VRE colonization after 3 negative stool cultures (Study B). Twelve patients had stored VRE isolates recovered > 1 year apart (Study A), and 58% of paired isolates were genotypically related according to pulsed field gel electrophoresis patterns. In Study B, stool samples were obtained weekly from 21 "cleared" patients for 5 weeks, which revealed that 24% were VRE positive. For these culture-positive patients, 72% of the cultures failed to detect VRE. Recent antibiotic use was significantly more common in the culture-positive patients, as compared with culture-negative patients (P=.003). Colonization with VRE may persist for years, even if the results of intercurrent surveillance stool and index site cultures are negative. Cultures for detection of VRE in stool samples obtained from patients declared "cleared" are insensitive.
Assuntos
Enterococcus faecium/efeitos dos fármacos , Enterococcus faecium/crescimento & desenvolvimento , Infecções por Bactérias Gram-Positivas/microbiologia , Resistência a Vancomicina/genética , Meios de Cultura , Eletroforese em Gel de Campo Pulsado , Enterococcus faecium/classificação , Enterococcus faecium/isolamento & purificação , Fezes/microbiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , Hospitais de Veteranos , Humanos , Assistência de Longa Duração , Testes de Sensibilidade Microbiana/métodosRESUMO
Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for an increasing number of serious nosocomial and community-acquired infections. Phenotypic heterogeneous drug resistance (heteroresistance) to antistaphylococcal beta-lactams affects the results of susceptibility testing. The present study compared the MRSA-Screen latex agglutination test (Denka Seiken Co., Ltd., Tokyo, Japan) for detection of PBP 2a with agar dilution, the VITEK-1 and VITEK-2 systems (bioMérieux, St. Louis, Mo.), and the oxacillin agar screen test for detection of MRSA, with PCR for the mecA gene used as the "gold standard" assay. Analysis of 107 methicillin-susceptible S. aureus (MSSA) isolates and 203 MRSA isolates revealed that the MRSA-Screen latex agglutination test is superior to any single phenotype-based susceptibility testing method, with a sensitivity of 100% and a specificity of 99.1%. Only one isolate that lacked mecA was weakly positive by the MRSA-Screen latex agglutination test. This isolate was phenotypically susceptible to oxacillin and did not contain the mecA gene by Southern blot hybridization. The oxacillin agar screen test, the VITEK-1 system, the VITEK-2 system, and agar dilution showed sensitivities of 99.0, 99.0, 99.5, and 99%, respectively, and specificities of 98.1, 100, 97.2, and 100%, respectively. The differences in sensitivity or specificity were not statistically significant. Oxacillin bactericidal assays showed that mecA- and PBP 2a-positive S. aureus isolates that are susceptible to antistaphylococcal beta-lactams by conventional methods are functionally resistant to oxacillin. We conclude that the accuracy of the MRSA-Screen latex agglutination method for detection of PBP 2a approaches the accuracy of PCR and is more accurate than any susceptibility testing method used alone for the detection of MRSA.
Assuntos
Antibacterianos/farmacologia , Hexosiltransferases , Resistência a Meticilina/genética , Oxacilina/farmacologia , Penicilinas/farmacologia , Peptidil Transferases , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/farmacologia , Proteínas de Bactérias/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Humanos , Testes de Fixação do Látex , Testes de Sensibilidade Microbiana/métodos , Muramilpentapeptídeo Carboxipeptidase/genética , Muramilpentapeptídeo Carboxipeptidase/metabolismo , Proteínas de Ligação às Penicilinas , Sensibilidade e Especificidade , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/classificação , Staphylococcus aureus/genéticaRESUMO
While the concept of plaque 'vulnerability' implies a propensity towards thrombosis, the term vulnerable was originally intended to provide a morphologic description consistent with plaques that are prone to rupture. It is now known that the etiology of coronary thrombi is diverse and can arise from entities of plaque erosion or calcified nodules. These findings have prompted the search for more definitive terminology to describe precursor lesions associated with rupture, now referred to as thin-cap fibroatheromas. This review focuses on the thin-cap fibroatheroma, as a specific cause of acute coronary syndromes. To put these issues into current perspective, we need to revisit some of the older literature describing plaque morphology in stable and unstable angina, acute myocardial infarction, and sudden coronary death. The morphology, frequency, and precise location of these thin-cap fibroatheromas are further discussed in detail. Potential mechanisms of fibrous cap thinning are also addressed, in particular emerging data, which suggests the role of cell death "apoptosis" in cap atrophy.
Assuntos
Doença da Artéria Coronariana/fisiopatologia , Doença Aguda , Angina Pectoris/epidemiologia , Angina Pectoris/etiologia , Angina Pectoris/fisiopatologia , Doença da Artéria Coronariana/epidemiologia , Trombose Coronária/complicações , Trombose Coronária/epidemiologia , Trombose Coronária/fisiopatologia , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Humanos , Incidência , Ruptura Espontânea/fisiopatologiaRESUMO
The new oxazolidinone antimicrobial, linezolid, has been approved for the treatment of infections caused by various gram-positive bacteria, including meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Although instances of linezolid resistance in VRE have been reported, resistance has not been encountered among clinical isolates of S aureus. We have characterised an MRSA isolate resistant to linezolid that was recovered from a patient treated with this agent for dialysis-associated peritonitis.
Assuntos
Acetamidas/farmacologia , Antibacterianos/farmacologia , Oxazolidinonas/farmacologia , Inibidores da Síntese de Proteínas/farmacologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Acetamidas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Resistência Microbiana a Medicamentos , Humanos , Linezolida , Masculino , Resistência a Meticilina , Oxazolidinonas/uso terapêutico , Peritonite/tratamento farmacológico , Peritonite/microbiologia , Inibidores da Síntese de Proteínas/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológicoRESUMO
BACKGROUND: Pneumococcal immunization has been shown to be cost effective, is recommended by the Advisory Committee on Immunization Practices, and is covered by Medicare. Despite that, over 50% of the population aged > or =65 is not vaccinated, leading to significant mortality and morbidity. The objective of this study is to evaluate the costs and the cost utility of immunization in nontraditional settings (community clinics set up to provide influenza and pneumococcal vaccinations) as a strategy to increase pneumococcal immunization rates. METHODS: A cost-utility analysis of public immunization clinics in Monroe County, New York, during the fall of 1998. The study included 1207 adults aged > or =65. Costs of operating the clinics and of vaccine administration were measured. The cost of health sequela and estimates of quality-adjusted life years (QALYs) were obtained from prior studies. Sensitivity analyses were performed to test several important assumptions. RESULTS: Unlike immunizations in physician offices, immunizations in nontraditional settings are not cost saving. Estimates of incremental cost-utility ratios ranged from $4215 per QALY to $12,617 per QALY, depending on the underlying assumptions of the model. CONCLUSIONS: Clinics in nontraditional settings offering pneumococcal immunization have cost-utility ratios near and below those of other recommended vaccines. These results suggest that such clinics should be considered a viable strategy for increasing pneumococcal immunization rates.
Assuntos
Centros Comunitários de Saúde/economia , Serviços de Saúde para Idosos/economia , Imunização/economia , Vacinas Pneumocócicas/economia , Prática de Saúde Pública/economia , Idoso , Centros Comunitários de Saúde/normas , Análise Custo-Benefício , Custos de Cuidados de Saúde/estatística & dados numéricos , Pesquisa sobre Serviços de Saúde , Serviços de Saúde para Idosos/normas , Humanos , Imunização/estatística & dados numéricos , New York , Avaliação de Programas e Projetos de Saúde , Prática de Saúde Pública/normas , Garantia da Qualidade dos Cuidados de Saúde , Anos de Vida Ajustados por Qualidade de Vida , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: We sought to evaluate the ability of type 5 phosphodiesterase (PDE5) inhibitors to augment the antithrombotic effects of inhaled nitric oxide (NO) in a canine model of platelet-mediated coronary thrombosis after thrombolysis. BACKGROUND: Type 5 phosphodiesterase inhibitors potentiate the ability of NO to inhibit platelet aggregation in vitro by preventing platelet cyclic guanosine monophosphate catabolism. We previously reported that breathing low concentrations of NO gas attenuated, but did not prevent, cyclic flow reductions (CFRs) in a canine model of coronary thrombosis after thrombolysis. METHODS: Cyclic flow reductions were induced after creation of a left anterior descending coronary artery stenosis, endothelial injury, thrombus formation and thrombolysis. Dogs were either untreated or treated with inhaled NO (20 ppm by volume), intravenous zaprinast, intravenous dipyridamole or the combination of inhaled NO with either PDE5 inhibitor (n = 4 per group). RESULTS: Cyclic flow reductions ceased, and complete coronary patency was achieved in all dogs after they breathed NO combined with zaprinast (by 12.0+/-4.7 min [mean +/- SEM]) or dipyridamole (by 9.8+/-4.7 min). The frequency of CFRs was unaffected by NO, dipyridamole or zaprinast alone. Systemic arterial blood pressure and bleeding time were unchanged with any treatment. Ex vivo thrombin-induced platelet aggregation in dogs breathing NO and receiving dipyridamole was reduced by 75+/-7% (p < 0.05). CONCLUSIONS: The PDE5 inhibitors potentiated the antithrombotic properties of inhaled NO in a canine model of platelet-mediated coronary artery thrombosis after thrombolysis, without prolonging the bleeding time or causing systemic hypotension.
Assuntos
Plaquetas , Trombose Coronária/tratamento farmacológico , Dipiridamol/uso terapêutico , Óxido Nítrico/administração & dosagem , Inibidores de Fosfodiesterase/uso terapêutico , Purinonas/uso terapêutico , Terapia Trombolítica , Administração por Inalação , Animais , Cães , Quimioterapia CombinadaRESUMO
Enterococci are not generally regarded as highly virulent bacterial pathogens. However, resistance to many antimicrobial drugs complicates treatment of enterococcal infections. Acquired resistance to high concentrations of glycopeptide antibiotics, specifically vancomycin, has exacerbated this problem. This article seeks to concisely review the mechanisms of that resistance and its effects on clinical management of enterococcal infections, as well as clinical microbiology and infection control.
Assuntos
Enterococcus/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/microbiologia , Resistência a Vancomicina , Antibacterianos/farmacologia , Tomada de Decisões , Enterococcus/classificação , Enterococcus/genética , Genótipo , Glicopeptídeos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/prevenção & controle , Humanos , Laboratórios Hospitalares , FenótipoAssuntos
Bacteriemia/tratamento farmacológico , Meticilina/uso terapêutico , Penicilinas/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Bacteriemia/microbiologia , Quimioterapia Combinada/uso terapêutico , Humanos , Masculino , Resistência a Meticilina , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificaçãoRESUMO
OBJECTIVE: To determine risk factors for vancomycin-resistant Enterococcus (VRE) colonization during a hospital outbreak and to evaluate Centers for Disease Control and Prevention (CDC)-recommended control measures. DESIGN: Epidemiological study involving prospective identification of colonization and a case-control study. SETTING: A university hospital. PARTICIPANTS: Patients on eight wards involved in outbreak from late 1994 through early 1995. METHODS: Cases were matched by ward and culture date with up to two controls. Risk factors were evaluated with four multivariate models using conditional logistic regression. The first evaluated proximity to other VRE patients and isolation status. The second evaluated proximity to unisolated VRE cases and three variables independently predictive after adjustment for proximity. The third evaluated seven significant univariate predictors in addition to proximity to unisolated VRE in backward, stepwise logistic regression. The fourth assessed proximity to VRE with all other variables collected, clustered in a principal components analysis. Pulsed-field gel electrophoresis was performed to assess clonality of two outbreak strains. RESULTS: The incidence of transmission declined significantly after CDC guidelines were implemented. Proximity to unisolated VRE cases during the prior week was a significant predictor of acquisition in each of four multivariate models. Other significant risk factors in multivariate models included a history of major trauma and treatment with metronidazole. Pulsed-field gel electrophoresis confirmed the clonality of two outbreak strains. CONCLUSIONS: VRE was transmitted between patients during a hospital epidemic, with proximity to previously unisolated VRE patients being an important risk factor. Weekly surveillance cultures and contact isolation of colonized patients significantly reduced spread
Assuntos
Surtos de Doenças/prevenção & controle , Enterococcus faecalis/isolamento & purificação , Enterococcus faecium/isolamento & purificação , Infecções por Bactérias Gram-Positivas/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Feminino , Hospitais Universitários , Humanos , Incidência , Lactente , Unidades de Terapia Intensiva , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Resistência a Vancomicina , Virginia/epidemiologiaRESUMO
We assessed the ability of gene transfer to reverse vancomycin resistance in class A (VanA) glycopeptide-resistant Enterococcus faecalis. Recombinant shuttle vectors containing a vanH promoter-vanA antisense gene cassette fully restored vancomycin susceptibility through a combined transcriptional activator binding domain decoy and inducible vanA antisense RNA effect.
Assuntos
Antibacterianos/farmacologia , Enterococcus faecalis/genética , Oligonucleotídeos Antissenso/farmacologia , Resistência a Vancomicina/genética , Vancomicina/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Carbono-Oxigênio Ligases/antagonistas & inibidores , Carbono-Oxigênio Ligases/genética , Interações Medicamentosas , Enterococcus faecalis/efeitos dos fármacos , Técnicas de Transferência de Genes , Vetores Genéticos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Oligonucleotídeos Antissenso/genética , Transformação BacterianaRESUMO
Clinical, demographic and laboratory data from infants with congenital hypothyroidism (CH) born in the Australian state of Victoria from the commencement of neonatal screening in mid-1977 until December 1988 are reported. These provide a baseline for a 12-year prospective longitudinal study on physical and neuro-psychological outcome until mid-1997, the subject of a second paper. Infants with CH were detected using a primary TT4 screening test. Demographic data were collected prospectively using a clinical assessment protocol. Nearly all affected infants underwent 99mTc pertechnetate scanning at the initial assessment to determine the underlying aetiology of their hypothyroidism. 704,723 infants were screened and 199 with permanent primary hypothyroidism (one in 3,541) were identified. The most common aetiologies were thyroid ectopia (46%), thyroid aplasia (33%), and 'dyshormonogenesis' (11%). The clinical abnormalities classically described in CH were more evident in infants with aplasia, and the striking female preponderance in infants with thyroid dysplasia (syn. dysgenesis) was confirmed. Other features included increased frequencies of 'dyshormonogenesis' in infants of parents of Middle-Eastern origin and of labour induction in infants with dysplasia. A closed posterior fontanelle was not found in any infant with thyroid aplasia.
Assuntos
Hipotireoidismo Congênito , Hipotireoidismo/diagnóstico , Doenças do Recém-Nascido/diagnóstico , Programas de Rastreamento/métodos , Determinação da Idade pelo Esqueleto , Austrália , Demografia , Erros de Diagnóstico , Doenças em Gêmeos , Feminino , Humanos , Hipotireoidismo/classificação , Hipotireoidismo/epidemiologia , Incidência , Recém-Nascido , Doenças do Recém-Nascido/classificação , Doenças do Recém-Nascido/epidemiologia , Estudos Longitudinais , Masculino , Prontuários Médicos , Pais , Gravidez , Gravidez Prolongada , Estudos Prospectivos , Cintilografia , Testes de Função TireóideaRESUMO
A patient with carbohydrate-deficient glycoprotein syndrome type 1b (CDGS1b) is reported. The patient presented at 5 months of age with failure to thrive, prolonged diarrhoea, hepatomegaly and elevated serum liver transaminases. Liver biopsy showed steatosis. A low serum albumin and elevated serum liver transaminases persisted throughout childhood during which he had repeated infectious illnesses. From the age of 10 years he had oesophageal and duodenal ulceration together with recurrent bacterial cholangitis. Liver biopsy demonstrated hepatic fibrosis. CDGS1b was suspected, supported by the finding of a protein-losing enteropathy and finally confirmed by showing a reduced phosphomannoseisomerase activity. This case illustrates a rare condition with a wide range of presentations.
Assuntos
Defeitos Congênitos da Glicosilação/diagnóstico , Manose-6-Fosfato Isomerase/deficiência , Manose/uso terapêutico , Adolescente , Defeitos Congênitos da Glicosilação/tratamento farmacológico , Defeitos Congênitos da Glicosilação/enzimologia , Diagnóstico Diferencial , Humanos , Lactente , Masculino , Manose-6-Fosfato Isomerase/biossíntese , Resultado do TratamentoRESUMO
The highly conserved central loop of domain V of 23S RNA (nucleotides 2042 to 2628; Escherichia coli numbering) is implicated in peptidyltransferase activity and represents one of the target sites for macrolide, lincosamide, and streptogramin B antibiotics. DNA encoding domain V (590 bp) of several species of Enterococcus was amplified by PCR. Twenty enterococcal isolates were tested, including Enterococcus faecium (six isolates), Enterococcus faecalis, Enterococcus avium, Enterococcus durans, Enterococcus gallinarum, Enterococcus casseliflavus (two isolates of each), and Enterococcus raffinosus, Enterococcus mundtii, Enterococcus malodoratus, and Enterococcus hirae (one isolate of each). For all isolates, species identification by biochemical testing was corroborated by 16S rRNA gene sequencing. The sequence of domain V of the 23S rRNA gene from E. faecium and E. faecalis differed from those of all other enterococci. The domain V sequences of E. durans and E. hirae were identical. This was also true for E. gallinarum and E. casseliflavus. E. avium differed from E. casseliflavus by 23 bases, from E. durans by 16 bases, and from E. malodoratus by 2 bases. E. avium differed from E. raffinosus by one base. Despite the fact that domain V is considered to be highly conserved, substantial differences were identified between several enterococcal species.
Assuntos
Enterococcus/genética , Genes de RNAr/genética , Variação Genética , Infecções por Bactérias Gram-Positivas/microbiologia , RNA Ribossômico 23S/genética , Animais , Enterococcus/isolamento & purificação , Genes Bacterianos , Humanos , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase , RNA Ribossômico 23S/química , Análise de Sequência de DNARESUMO
Three sets of carbapenem-resistant Serratia marcescens isolates have been identified in the United States: 1 isolate in Minnesota in 1985 (before approval of carbapenems for clinical use), 5 isolates in Los Angeles (University of California at Los Angeles [UCLA]) in 1992, and 19 isolates in Boston from 1994 to 1999. All isolates tested produced two beta-lactamases, an AmpC-type enzyme with pI values of 8.6 to 9.0 and one with a pI value of approximately 9.5. The enzyme with the higher pI in each strain hydrolyzed carbapenems and was not inhibited by EDTA, similar to the chromosomal class A SME-1 beta-lactamase isolated from the 1982 London strain S. marcescens S6. The genes encoding the carbapenem-hydrolyzing enzymes were cloned in Escherichia coli and sequenced. The enzyme from the Minnesota isolate had an amino acid sequence identical to that of SME-1. The isolates from Boston and UCLA produced SME-2, an enzyme with a single amino acid change relative to SME-1, a substitution from valine to glutamine at position 207. Purified SME enzymes from the U. S. isolates had beta-lactam hydrolysis profiles similar to that of the London SME-1 enzyme. Pulsed-field gel electrophoresis analysis revealed that the isolates showed some similarity but differed by at least three genetic events. In conclusion, a family of rare class A carbapenem-hydrolyzing beta-lactamases first described in London has now been identified in S. marcescens isolates across the United States.