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1.
J Clin Microbiol ; 58(10)2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32817226

RESUMO

Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. There are limited data in the United States on the molecular epidemiological characteristics of M. pneumoniae We collected 446 M. pneumoniae-positive specimens from 9 states between August 2012 and October 2018. Culture, antimicrobial susceptibility testing, P1 subtyping, and multilocus VNTR (variable-number tandem repeats) analysis (MLVA) were performed to characterize the isolates. Macrolide-resistant M. pneumoniae (MRMp) was detected in 37 (8.3%) specimens. P1 subtype 2 (P1-2) was the predominant P1 subtype (59.8%). P1 subtype distribution did not change significantly chronologically or geographically. The macrolide resistance rate in P1 subtype 1 (P1-1) samples was significantly higher than that in P1-2 (12.9% versus 5.5%). Six P1-2 variants were identified, including two novel types, and variant 2c was predominant (64.6%). P1-2 variants were distributed significantly differently among geographic regions. Classical P1-2 was more frequent in lower respiratory tract specimens and had longer p1 trinucleotide repeats. Classical P1-2 was most common in MRMp (35.7%), while variant 2c was most common in macrolide-susceptible M. pneumoniae (67.5%). Fifteen MLVA types were identified; 3-5-6-2 (41.7%), 4-5-7-2 (35.3%), and 3-6-6-2 (16.6%) were the major types, and four MLVA clusters were delineated. The distribution of MLVA types varied significantly over time and geographic location. The predominant MLVA type switched from 4-5-7-2 to 3-5-6-2 in 2015. MLVA type was associated with P1 subtypes and P1-2 variant types but not with macrolide resistance. To investigate the M. pneumoniae genotype shift and its impact on clinical presentations, additional surveillance programs targeting more diverse populations and prolonged sampling times are required.


Assuntos
Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Genótipo , Humanos , Macrolídeos/farmacologia , Mycoplasma pneumoniae/genética , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/epidemiologia , Estados Unidos/epidemiologia
2.
J Clin Microbiol ; 58(6)2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32269102

RESUMO

We evaluated six commercial molecular tests targeting Mycoplasma pneumoniae, namely, the BioFire FilmArray respiratory panel (RP), the Meridian Alethia Mycoplasma Direct, the GenMark ePlex respiratory pathogen panel (RPP), the Luminex NxTAG RPP, the ELITech ELITe InGenius Mycoplasma MGB research use only (RUO) PCR, and the SpeeDx Resistance Plus MP assays. Laboratory-developed PCR assays at the University of Alabama at Birmingham and the Centers for Disease Control and Prevention were used as reference standards. Among 428 specimens, 212 were designated confirmed positives for M. pneumoniae The highest clinical sensitivities were found with the InGenius PCR (99.5%) and the FilmArray RP (98.1%). The Resistance Plus MP identified 93.3% of the confirmed-positive specimens, whereas 83.6, 64.6, and 55.7% were identified by the ePlex RPP, NxTAG RPP, and Mycoplasma Direct assays, respectively. There was no significant difference between the sensitivity of the reference methods and that of the FilmArray RP and InGenius assays, but the remaining four assays detected significantly fewer positive specimens (P < 0.05). Specificities of all assays were 99.5 to 100%. The Resistance Plus MP assay detected macrolide resistance in 27/33 specimens, resulting in a sensitivity of 81.8%. This study provides the first large-scale comparison of commercial molecular assays for detection of M. pneumoniae in the United States and identified clear differences among their performance. Additional studies are necessary to explore the impact of various test performances on patient outcome.


Assuntos
Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Humanos , Macrolídeos/farmacologia , Mycoplasma pneumoniae/genética , Patologia Molecular , Pneumonia por Mycoplasma/diagnóstico
3.
Diabet Med ; 37(12): 1966-1976, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31631398

RESUMO

AIM: To summarize and evaluate the existing evidence on the effectiveness of distal technology with regard to multiple health outcomes in people with diabetes. METHODS: We searched PubMed, EMBASE and the Cochrane Database of Systematic Reviews from database inception to 31 August 2018 for systematic reviews and/or meta-analyses of studies that examined the impact of distal technology and reported any clinical or patient-related outcomes among people with type 1 or type 2 diabetes. RESULTS: The umbrella review identified 95 reviews, including 162 meta-analyses with 46 unique outcomes. Evidence from meta-analyses of randomized controlled studies supports the use of distal technology, especially telehealth and mHealth (healthcare delivered by mobile technology), in people with diabetes for improving HbA1c values by 2-4 mmol/mol (0.2-0.4%). For other health outcomes, such as changes in fasting plasma glucose levels, risk of diabetic ketoacidosis or frequency of severe hypoglycaemia, the evidence was weaker. No evidence was reported for most patient-reported outcomes including quality of life, self-efficacy and medication-taking. The evidence base was poor, with most studies rated as low to very low quality. CONCLUSION: Distal technologies were associated with a modest improvement in glycaemic control, but it was unclear if they improved major clinical outcomes or were cost-effective in people with diabetes. More robust research to improve wider outcomes in people with diabetes is needed before such technologies can be recommended as part of routine care for any patient group.


Assuntos
Diabetes Mellitus/terapia , Aplicativos Móveis , Portais do Paciente , Mídias Sociais , Telemedicina , Envio de Mensagens de Texto , Glicemia/metabolismo , Diabetes Mellitus/metabolismo , Cetoacidose Diabética/epidemiologia , Correio Eletrônico , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/uso terapêutico , Avaliação de Resultados da Assistência ao Paciente , Literatura de Revisão como Assunto
4.
J Clin Microbiol ; 57(11)2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31484701

RESUMO

There are sparse data to indicate the extent that macrolide-resistant Mycoplasma pneumoniae (MRMp) occurs in the United States or its clinical significance. Between 2015 and 2018, hospitals in 8 states collected and stored respiratory specimens that tested positive for M. pneumoniae and sent them to the University of Alabama at Birmingham, where real-time PCR was performed for detection of 23S rRNA mutations known to confer macrolide resistance. MRMp was detected in 27 of 360 specimens (7.5%). MRMp prevalence was significantly higher in the South and East (18.3%) than in the West (2.1%). A2063G was the predominant 23S rRNA mutation detected. MICs for macrolide-susceptible M. pneumoniae (MSMp) were ≤0.008 µg/ml, whereas MICs for MRMp were 16 to 32 µg/ml. Patients with MRMp infection were more likely to have a history of immunodeficiency or malignancy. Otherwise, there were no other significant differences in the clinical features between patients infected with MRMp and those infected with MSMp, nor were there any differences in radiographic findings, hospitalization rates, viral coinfections, the mean duration of antimicrobial treatment, or clinical outcomes. There was no significant change in MRMp incidence over time or according to age, sex, race/ethnicity, or status as an inpatient or an outpatient. Patients with MRMp were more likely to have received a macrolide prior to presentation, and their treatment was more likely to have been changed to a fluoroquinolone after presentation. This is the first national surveillance program for M. pneumoniae in the United States. Additional surveillance is needed to assess the clinical significance of MRMp and to monitor changes in MRMp prevalence.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Macrolídeos/farmacologia , Mycoplasma pneumoniae/efeitos dos fármacos , Pneumonia por Mycoplasma/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Monitoramento Epidemiológico , Feminino , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação , Mycoplasma pneumoniae/genética , Pneumonia por Mycoplasma/microbiologia , Prevalência , RNA Ribossômico 23S/genética , Estados Unidos/epidemiologia , Adulto Jovem
5.
Eur J Clin Microbiol Infect Dis ; 36(9): 1665-1672, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28429164

RESUMO

We compared the frequency of gastrointestinal (GI) pathogen detection in an oncology patient population by two multiplexed molecular assays, the Luminex xTAG® Gastrointestinal Pathogen Panel (GPP, which identifies 14 GI pathogens) and the BioFire Gastrointestinal Panel (BFGP, which identifies 22 GI pathogens). We additionally reviewed the clinical characteristics of patients tested with both panels. A total of 200 prospectively collected and 81 archived stool samples were tested by both panels. In the prospective cohort, the GPP and BFGP identified a pathogen in 33.5% [95% confidence interval (CI): 27.3-40.35%] and 39.6% (95% CI: 33.0%-46.6%) of samples, respectively (p = 0.25). The BFGP detected significantly more pathogens than the GPP (p = 0.038), with 21.3% of samples positive for targets only detected by the BFGP. The concordance between the assays was very good at 91.1% (κ = 0.8, 95% CI: 0.7-0.9) when considering only pathogens detected by both assays. The most frequent pathogens detected were Clostridium difficile, norovirus, Campylobacter, and Salmonella species. On the archived samples, the BFGP was positive in 92.6% of samples but detected more pathogens than the GPP (86 vs. 97, p = 0.033), including both targets unique to the BFGP and targets common to both panels. A pathogen was more frequently detected in patients with hematological malignancies than solid tumors and in ambulatory patients compared to hospitalized patients, but these differences were not statistically significant. Overall, the detection rates were similar for both the GPP and the BFGP, and the latter detected more than one pathogen in additional patients. The impact of increased detection of GI pathogens by multiplexed panels on the clinical care of oncology patients will require further investigation.


Assuntos
Gastroenterite/etiologia , Microbioma Gastrointestinal , Neoplasias/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Fezes/microbiologia , Feminino , Gastroenterite/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Metagenoma , Metagenômica/métodos , Pessoa de Meia-Idade , Neoplasias/terapia , Adulto Jovem
6.
Phys Chem Chem Phys ; 18(39): 27078-27082, 2016 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-27711679

RESUMO

A one dimensional nanostructure array has been considered as a successful charge transport material for perovskite solar cells (PSCs), because of its large internal surface area, superior charge collection efficiency and fast charge transport. Herein we demonstrate a ZnO nanorod (NR) array as the electron collector in a hole-conductor-free PSC with a carbon counter electrode (CE). A relatively low initial power conversion efficiency (PCE) of 5.6% was achieved using a 1 µm long ZnO NR array as an electron collector. However, by introduction of a thin TiO2 coating layer on the surface of ZnO via TiCl4 treatment, the PCE of the cell has been improved to the highest value of 8.24%. It is revealed that the performance enhancement of the ZnO/TiO2 NR based PSCs is largely attributed to the larger surface area, reduced electron combination, and superior electron transport properties.

7.
Genet Mol Res ; 15(4)2016 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-27819745

RESUMO

The abscisic acid (ABA) signaling pathway is known as one of the most important signaling pathways in plants and is mediated by multiple regulators. The genes SnRK2, PYR/PYL/RCAR, and ABF are relevant to both ABA-dependent and -independent signaling pathways. To elucidate the profile of these genes from Tibetan hulless barley (Hordeum vulgare L. var. nudum Hook. f.), we collected available sequences from RNA-Seq data, together with NCBI data from five other model plant species (Arabidopsis thaliana, Brachypodium distachyon, Oryza sativa, Populus trichocarpa, and Sorghum bicolor). Gene trees of SnRK2, PYR/PYL/RCAR, and ABF were constructed using a neighbor joining (NJ) method. For all genes, we identified a dominant group in which all six species were represented. Three, four, and five groups were found in the NJ trees of SnRK2, PYR/PYL/RCAR, and ABF, respectively. For each gene, Tibetan hulless barley was divided into three groups. Our analyses indicated that Tibetan hulless barley was associated with B. distachyon. The NJ cluster analysis also suggested that Tibetan hulless barley was affiliated with S. bicolor (SnRK2), A. thaliana (PYR/PYL/RCAR), and O. sativa (ABF). These results illustrate a diverse expression of genes SnRK2, PYR/PYL/RCAR, and ABF, and suggest a relationship among the six species studied. Collectively, our characterization of the three components of the ABA signaling pathway may contribute to improve stress tolerance in Tibetan hulless barley.


Assuntos
Genes de Plantas , Hordeum/genética , Filogenia , Análise por Conglomerados , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
9.
Eur J Clin Microbiol Infect Dis ; 33(1): 23-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23856883

RESUMO

Gonococcal endocarditis is rarely encountered in the post-antibiotic era. This case report describes a case of a previously healthy male who presented with double quotidian fever, chills, cough, and urethral symptoms. The presence of a cardiac mitral valvular vegetation along with positive blood cultures for Neisseria gonorrhoeae were diagnostic for gonococcal endocarditis. This case was, to our knowledge, the first reported gonococcal endocarditis case in China.


Assuntos
Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/microbiologia , Gonorreia/complicações , Neisseria gonorrhoeae/isolamento & purificação , Adulto , Sangue/microbiologia , China , Endocardite Bacteriana/patologia , Humanos , Masculino , Valva Mitral/microbiologia , Valva Mitral/patologia
10.
J Hosp Infect ; 149: 104-107, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38670494

RESUMO

OBJECTIVES: Antiseptics such as chlorhexidine gluconate (CHG) and octenidine dihydrochloride (OCT) are frequently used in hospitals to prevent and control the transmission of meticillin-resistant Staphylococcus aureus (MRSA). Given the increasing prevalence of reduced CHG susceptibility of MRSA, there are concerns about the possibility of reduced OCT susceptibility. This study evaluated the prevalence of reduced CHG and OCT susceptibility over 3 years, and assessed the association between OCT exposure and reduced OCT susceptibility in MRSA. METHODS: MRSA isolates from inpatients who acquired MRSA in an extended-care facility between 2019 and 2021 were included in antiseptic susceptibility testing. Inpatients were exposed to universal daily CHG bathing from January to September 2019, and universal daily OCT bathing after October 2019. The minimum inhibitory concentrations (MICs) of CHG and OCT were determined using the broth microdilution method. Multi-variable logistic regression was used to assess if OCT exposure was independently associated with reduced OCT susceptibility. RESULTS: Of 186 isolates, 179 (96%) had reduced CHG susceptibility (MIC ≥4 mg/L) and 46 (25%) had reduced OCT susceptibility (MIC ≥2 mg/L). Reduced OCT susceptibility rates were 26.9%, 13.8% and 14.3% in 2019, 2020 and 2021, respectively. Reduced CHG susceptibility rates were 95.4%, 100% and 95.9% in 2019, 2020 and 2021, respectively. OCT exposure was not associated with reduced OCT susceptibility (adjusted odds ratio 0.23, 95% confidence interval 0.08-0.75; P=0.014), after adjusting for age, gender, race, year of sample collection, days at risk in facility, hospitalization in preceding year, and MRSA colonization/infection in preceding year. CONCLUSION: The prevalence of reduced OCT susceptibility has remained low, despite universal OCT bathing for extended inpatient care. However, the rate of reduced CHG susceptibility was high. OCT exposure was not associated with reduced OCT susceptibility in MRSA.


Assuntos
Anti-Infecciosos Locais , Iminas , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Piridinas , Infecções Estafilocócicas , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Singapura/epidemiologia , Anti-Infecciosos Locais/farmacologia , Feminino , Masculino , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Pessoa de Meia-Idade , Idoso , Piridinas/farmacologia , Clorexidina/farmacologia , Clorexidina/análogos & derivados , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Idoso de 80 Anos ou mais , Adulto
11.
Eur J Clin Microbiol Infect Dis ; 31(3): 217-23, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21643868

RESUMO

The objective of this paper was to investigate the sequence types (STs) and diversity of surface antigen pneumococcal surface protein A (PspA) in 171 invasive Streptococcus pneumoniae isolates from Chinese children. A total of 171 pneumococci isolates were isolated from Chinese children with invasive pneumococcal diseases (IPD) in 11 hospitals between 2006 and 2008. The pneumococci samples were characterized by serotyping, PspA classification, and multilocus sequence typing (MLST). The PspA of these strains could be assigned to two families. The PspA family 2 was the most common (120/171, 70.1%). No PspA family 3 isolates were detected. Family 1 could be subdivided into two clades, with 42 strains in clade 1 and 9 strains in clade 2, and family 2 could be subdivided into clades 3, 4, and 5, which respectively contained 5, 21, and 14 strains. In total, 65 STs were identified, of which ST320 (30/171, 17.5%), ST271 (23/171, 13.5%), and ST876 (18/171, 10.5%) were the most common types. PspA family 2 and family 1 were dominant among pneumococcal clones isolated from Chinese children with invasive disease. The strains with the same ST always presented in the same PspA family.


Assuntos
Proteínas de Bactérias/classificação , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/classificação , Proteínas de Bactérias/genética , Técnicas de Tipagem Bacteriana , Criança , China , Variação Genética , Humanos , Tipagem de Sequências Multilocus , Vacinas Pneumocócicas , Sorotipagem , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação
12.
J Clin Microbiol ; 47(11): 3732-4, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19776231

RESUMO

Matrix-assisted laser desorption ionization-time of flight mass spectrometry has emerged as a rapid, cost-effective alternative for bacterial species identification. Identifying 60 blind-coded nonfermenting bacteria samples, this international study (using eight laboratories) achieved 98.75% interlaboratory reproducibility. Only 6 of the 480 samples were misidentified due to interchanges (4 samples) or contamination (1 sample) or not identified because of insufficient signal intensity (1 sample).


Assuntos
Bactérias Aeróbias/química , Bactérias Aeróbias/classificação , Infecções Bacterianas/diagnóstico , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Erros de Diagnóstico/estatística & dados numéricos , Reprodutibilidade dos Testes
13.
Clin Microbiol Infect ; 24(12): 1339.e7-1339.e12, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29549061

RESUMO

OBJECTIVE: To evaluate the impact of rapidly identifying coagulase-negative staphylococci (CoNS) from positive blood cultures combined with an established antimicrobial stewardship (AS) programme at a tertiary cancer centre. METHODS: We compared cancer patients ≥18 years old who between 01/1/13 and 12/31/13 had one or more positive CoNS blood culture(s) identified by Staphylococcus QuickFISH® (a peptide nucleic acid fluorescence in situ hybridization assay) with cancer patients ≥18 years old who had CoNS identified by standard microbiological techniques between 01/01/11 and 12/31/11 (baseline). Positive blood culture results were reported to the clinician by microbiology staff; restricted antibiotics (e.g., vancomycin) required approval by the AS team. RESULTS: There were 196 baseline and 103 QuickFISH patients. Faster median time to organism identification (33 (IQR 27-46) versus 49 (IQR 39-63) hours, p < 0.001), more vancomycin avoidance (51/103 (50%) versus 60/196 (31%), p 0.002), shorter median antibiotic duration (1 (IQR 0-3) versus 2 (IQR 0-6) days, p 0.019), fewer central venous catheter (CVC) removals (14/78 (18%) versus 57/160 (36%), p 0.004), and reduced vancomycin level monitoring (16/52 (31%) versus 71/136 (52%), p 0.009) were observed in the QuickFISH group. QuickFISH implementation was predictive of a lower likelihood of antibiotic therapy prescription (OR 0.35, 95%CI 0.20-0.62, p < 0.001). Prior transplant (RR 1.47, 95%CI 1.13-1.92, p 0.004), neutropenia (RR 1.47, 95%CI 1.09-1.99, p 0.012), multiple positive blood cultures (RR 4.23, 95%CI 3.23-5.54, p < 0.001), and CVC (RR 1.60, 95%CI 1.02-2.53, p 0.043) were independent factors for antibiotic duration. CONCLUSIONS: QuickFISH implementation plus AS support leads to greater avoidance of vancomycin therapy and improved resource utilization in cancer patients with CoNS blood cultures.


Assuntos
Gestão de Antimicrobianos/estatística & dados numéricos , Hibridização in Situ Fluorescente/estatística & dados numéricos , Neoplasias/microbiologia , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/diagnóstico , Staphylococcus/isolamento & purificação , Vancomicina/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Técnicas Bacteriológicas , Hemocultura , Técnicas de Laboratório Clínico , Coagulase/deficiência , Feminino , Humanos , Hibridização in Situ Fluorescente/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus/enzimologia , Staphylococcus/genética , Vancomicina/uso terapêutico , Adulto Jovem
14.
J Clin Invest ; 94(5): 1953-8, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7962541

RESUMO

Upon respiratory syncytial virus (RSV) challenge, mice previously immunized intramuscularly with inactivated whole virus express a Th2-like pattern of cytokine mRNA, while mice immunized with live virus intranasally express a Th1-like pattern. In this study, we evaluated the effects of anti-IL-4 treatment on the induction of immune responses after immunization. Mice treated with anti-IL-4 at the time of immunization with inactivated RSV had reduced clinical illness after live virus challenge, as measured by weight loss, illness score, and virus replication. This was associated with an augmented CD8+ cytotoxic T lymphocyte (CTL) activity, increased expression of IFN-gamma mRNA relative to IL-4 mRNA, and a higher titer of RSV-specific IgG2a in the anti-IL-4 treated mice before challenge. Anti-IL-4 administration at the time of challenge had no effects on illness, immunoglobulin isotype, or cytokine patterns. These results suggest that inhibition of IL-4 action at immunization can shift the selective activation of lymphocytes to a more Th1-like response. This cytokine milieu is associated with augmented CTL activity, which may be the factor responsible for rapid viral clearance and reduced illness at the time of remote RSV challenge.


Assuntos
Citocinas/biossíntese , Interleucina-4/imunologia , Vírus Sinciciais Respiratórios/imunologia , Linfócitos T Citotóxicos/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Monoclonais , Citocinas/genética , Citotoxicidade Imunológica , Feminino , Imunização , Isotipos de Imunoglobulinas/sangue , Camundongos , Camundongos Endogâmicos BALB C
15.
J Clin Invest ; 99(9): 2183-91, 1997 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-9151790

RESUMO

Manipulation of the cytokine microenvironment at the time of vaccination can influence immune responses to remote challenge, providing a strategy to study the molecular pathogenesis of respiratory syncytial virus (RSV) vaccine-enhanced disease in the mouse model. Although treatment with antibody against IL-4 or recombinant IL-12 (rIL-12) at the time of formalin-inactivated RSV vaccination induced a similar shift in the pattern of cytokine mRNA expression upon live virus challenge, anti-IL-4 treated mice had increased CD8+ cytotoxic T lymphocyte activity and reduced illness compared with rIL-12-treated mice. To define effector mechanisms responsible for these patterns, CD4+ and/or CD8+ T lymphocytes were selectively depleted in vivo at the time of RSV challenge. In rIL-12-treated mice, CD4+ lymphocytes made the largest contribution to IFN-gamma mRNA, RSV clearance, and illness, while in anti-IL-4 treated mice, CD8+ lymphocytes were the major effector. The effector responsible for virus clearance also mediated illness, suggesting that efficiency of virus clearance determined disease expression. These results demonstrate that the phenotype of effector cells involved in the immune response to virus challenge may be a more important determinant of disease than patterns of cytokine expression classically assigned to Th1 and Th2 lymphocytes.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Animais , Testes Imunológicos de Citotoxicidade , Relação Dose-Resposta Imunológica , Feminino , Isotipos de Imunoglobulinas/análise , Interferon gama/imunologia , Interleucina-12/imunologia , Interleucina-4/imunologia , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/análise , Proteínas Recombinantes/farmacologia , Células Th1/imunologia , Células Th2/imunologia , Vacinação
16.
Rev Sci Instrum ; 78(11): 113503, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18052470

RESUMO

A new multichannel HCN interferometer has been developed on HL-2A tokamak, which is characterized by two techniques: (1) the wave-guide HCN laser with cavity length of 6 m to increase the optical resource power and (2) high response room temperature waveguide Schottky diode detectors to obtain good beat signal. The space resolution is 7 cm by the use of focusing metal mirrors mounted on the vacuum chamber and a compensated optical system. In the 2006 experiment campaign, this new interferometer has been applied for plasma density profile and density sawtooth measurement.

17.
Virus Res ; 21(1): 35-52, 1991 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1962503

RESUMO

A cDNA containing the complete open reading frame of the M genome segment of Hantavirus R22 strain isolated from Rattus norvegicus in China, was amplified by polymerase chain reaction (PCR), and then cloned. The M segment is 3656 nucleotides in length with a predicted region of 3402 bases encoding a precursor glycoprotein of 1134 amino acids subsequently processed into viral glycoproteins 1 and 2 (G1 and G2). A strain comparison between R22 and SR11 (isolated from a rat in Japan), and Hantaan 76-118 (isolated from Apodemus in Korea), and Hallnas B1 (isolated from a bank vole in Sweden) revealed 95%, 74%, and 53% homologies at the deduced amino acid sequence level respectively. This suggests that the rodent host species may be a more important determinant of genetic relationships than geographic proximity. Six potential asparagine linked glycosylation sites (five in G1 and one in G2) were identified, and among them all are conserved in SR11, five in Hantaan virus and four in Hallnas B1 virus. Although different degrees of homology exist among these four viruses at amino acid sequence level, more than 90% of the cysteine residues are conserved, suggesting that structural homology may be very strong between the Hantaviruses. Genetic differences in the M segment genome of R22 and SR11 viruses, within the same serotype viruses, were found as random coding changes; some limited to single amino acids, others in clusters. A recombinant vaccinia virus that contained the fully activated M segment cDNA of R22 was constructed. This recombinant virus expressed two glycoproteins G1 and G2 identical to R22 virus G1 and G2 in molecular weight, cleavage pattern and cellular immunofluorescent patterns.


Assuntos
Glicoproteínas/genética , Orthohantavírus/genética , Proteínas Virais/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Southern Blotting , China , Clonagem Molecular , DNA Viral , Genes Virais , Vetores Genéticos , Orthohantavírus/isolamento & purificação , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Ensaio de Radioimunoprecipitação , Ratos , Vaccinia virus/genética
18.
Biomaterials ; 24(12): 2003-11, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12628819

RESUMO

The current study has investigated the influence of esterase activity (80-400units/ml) on the biodegradation of polycarbonate-urethanes (PCNUs) by cholesterol esterase (CE), with a particular interest in studying the influence of different hard segment structures and their contribution to sensitizing the polymer towards enzyme catalyzed hydrolysis. Polycarbonate based polyurethanes were synthesized with varying hard segment content as well as hard segment chemistry based on three different diisocyanates, 1,6-hexane diisocyanate (HDI), 4,4'-methylene bisphenyl diisocyanate (MDI) and 4,4-methylene biscyclohexyl diisocyanate (HMDI). The effect of different chemistry on surface contact angle was measured in order to define the relative chemical nature of the surfaces. The enzyme dose response was found to be lower when hard segment content in the polymer was high. There was a very strong dependence on enzyme concentration for polyurethanes with different hard segment chemistry, despite the fact that the nature of the hydrolysable polycarbonate segment remained the same. The PCNU which showed the most dramatic dependence on enzyme concentration was synthesized with HMDI. At low enzyme concentration (80units/ml) this material was the most stable of the polymers while at elevated CE concentration (400units/ml) the polymer underwent a catastrophic breakdown. The findings suggested that protein binding on the surfaces was saturated even though enzyme degradation did not achieve saturation on any of the surfaces. The role of protein binding in modulating the hydrolytic action of the enzymes at different activity levels highlights a need for further study in this area.


Assuntos
Cianatos/farmacologia , Enzimas/farmacologia , Cimento de Policarboxilato/química , Poliuretanos/química , Esterol Esterase/química , Esterol Esterase/farmacologia , Relação Dose-Resposta a Droga , Enzimas/química , Hidrólise , Isocianatos/farmacologia , Polímeros/química , Ligação Proteica , Temperatura
19.
Biomaterials ; 24(17): 2805-19, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12742719

RESUMO

Polycarbonate-polyurethanes (PCNUs) have provided the medical device industry with practical alternatives to oxidation-sensitive polyether-urethanes (PEUs). To date, many studies have focused on PCNUs synthesized with 4,4'-methylene diphenyl-diisocyanate (MDI). The relative hydrolytic stability of this class of polyurethanes is actually quite surprising given the inherent hydrolytic potential of the aliphatic carbonate group. Yet, there has been little information reporting on the rationale for the material's demonstrated hydrolytic stability. Recent work has shown that PCNU materials have a strong sensitivity towards hydrolysis when changes are made to their hard segment content and/or chemistry. However, knowledge is specifically lacking in regards of the identification of cleavage sites and the specific nature of the biodegradation products. Using high-performance liquid chromatography, radiolabel tracers and mass spectrometry, the current study provides insight into the distribution of biodegradation products from the enzyme-catalyzed hydrolysis of five different PCNUs. The hydrolytic sensitivity of the materials is shown to be related to the distribution of products, which itself is a direct consequence of unique micro-structures formed within the different materials. While an MDI-based polymer was shown to be the most hydrolytically stable material, it was the only PCNU that produced its diamine analog, in this case 4,4'-methylene dianiline (MDA), as a degradation product. Given the concern over aromatic diamine toxicity, this finding is important and highlights the fact that relative biostability is a distinct issue from that of degradation product toxicity, and that both must be considered separately when assessing the impact of biodegradation on biomaterial in vivo compatibility.


Assuntos
Compostos de Anilina/química , Compostos de Anilina/isolamento & purificação , Materiais Biocompatíveis/química , Teste de Materiais/métodos , Cimento de Policarboxilato/química , Poliuretanos/química , Esterol Esterase/química , Água/química , Biodegradação Ambiental , Hidrólise , Cimento de Policarboxilato/metabolismo , Poliuretanos/metabolismo , Solubilidade , Esterol Esterase/metabolismo , Água/metabolismo
20.
Biomaterials ; 18(1): 37-45, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9003895

RESUMO

Of the various polymers used in medical devices, polyurethanes have been relatively successful because of their acceptable mechanical and biological properties. However, over the past decade, increasing concerns have arisen in relation to long-term biostability of polyurethanes when exposed to the harsh environment of the human body. Lysosomal enzymes released from inflammatory cells have been proposed to be important mediators in the degradation of biomedical polyurethanes. In order to increase the biostability of polyurethanes to lysosomal enzymes, a series of surface-modifying macromolecules (SMMs) were synthesized in this work and then combined into a base polyurethane to reduce the material's susceptibility to hydrolysis. X-ray photoelectron spectroscopy (XPS) studies showed that the SMMs were enriched within the upper 10 nm of the surface. In vitro biodegradation test results indicated that the degradation of a polyester-urea-urethane could be inhibited by the new SMM surface. It was also found that different SMM formulations provided varying degrees of inhibition against the biodegradation of the polyester-urea-urethane. Certain formulations of the SMMs were shown to be physically incompatible with the polyurethane and distorted surface morphology to the extent that biodegradation was enhanced.


Assuntos
Lisossomos/enzimologia , Poliuretanos/química , Esterol Esterase/metabolismo , Biodegradação Ambiental , Estabilidade de Medicamentos , Hidrólise , Substâncias Macromoleculares , Poliésteres/síntese química , Poliésteres/química , Polímeros/síntese química , Polímeros/química , Poliuretanos/síntese química , Poliuretanos/metabolismo , Propriedades de Superfície
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