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91.
Vaccines against infectious bronchitis of chickens (Gallus gallus domesticus) have arguably been the most successful, and certainly the most widely used, of vaccines for diseases caused by coronaviruses, the others being against bovine, canine, feline and porcine coronaviruses. Infectious bronchitis virus (IBV), together with the genetically related coronaviruses of turkey (Meleagris gallopovo) and ring-necked pheasant (Phasianus colchicus), is a group 3 coronavirus, severe acute respiratory syndrome (SARS) coronavirus being tentatively in group 4, the other known mammalian coronaviruses being in groups 1 and 2.

IBV replicates not only in respiratory tissues (including the nose, trachea, lungs and airsacs, causing respiratory disease), but also in the kidney (associated with minor or major nephritis), oviduct, and in many parts of the alimentary tract—the oesophagus, proventriculus, duodenum, jejunum, bursa of Fabricius, caecal tonsils (near the distal end of the tract), rectum and cloaca (the common opening for release of eggs and faeces), usually without clinical effects. The virus can persist, being re-excreted at the onset of egg laying (4 to 5 months of age), believed to be a consequence of the stress of coming into lay.

Genetic lines of chickens differ in the extent to which IBV causes mortality in chicks, and in respect of clearance of the virus after the acute phase.

Live attenuated (by passage in chicken embryonated eggs) IBV strains were introduced as vaccines in the 1950s, followed a couple of decades later by inactivated vaccines for boosting protection in egg-laying birds. Live vaccines are usually applied to meat-type chickens at 1 day of age. In experimental situations this can result in sterile immunity when challenged by virulent homologous virus. Although 100% of chickens may be protected (against clinical signs and loss of ciliary activity in trachea), sometimes 10% of vaccinated chicks do not respond with a protective immune response. Protection is short lived, the start of the decline being apparent 9 weeks after vaccination with vaccines based on highly attenuated strains. IBV exists as scores of serotypes (defined by the neutralization test), cross-protection often being poor. Consequently, chickens may be re-vaccinated, with the same or another serotype, two or three weeks later.

Single applications of inactivated virus has generally led to protection of <50% of chickens. Two applications have led to 90 to 100% protection in some reports, but remaining below 50% in others. In practice in the field, inactivated vaccines are used in laying birds that have previously been primed with two or three live attenuated virus vaccinations. This increases protection of the laying birds against egg production losses and induces a sustained level of serum antibody, which is passed to progeny.

The large spike glycoprotein (S) comprises a carboxy-terminal S2 subunit (approximately 625 amino acid residues), which anchors S in the virus envelope, and an amino-terminal S1 subunit (approximately 520 residues), believed to largely form the distal bulbous part of S. The S1 subunit (purified from IBV virus, expressed using baculovirus or expressed in birds from a fowlpoxvirus vector) induced virus neutralizing antibody. Although protective immune responses were induced, multiple inoculations were required and the percentage of protected chickens was too low (<50%) for commercial application. Remarkably, expression of S1 in birds using a non-pathogenic fowl adenovirus vector induced protection in 90% and 100% of chickens in two experiments. Differences of as little as 5% between the S1 sequences can result in poor cross-protection. Differences in S1 of 2 to 3% (10 to 15 amino acids) can change serotype, suggesting that a small number of epitopes are immunodominant with respect to neutralizing antibody.

Initial studies of the role of the IBV nucleocapsid protein (N) in immunity suggested that immunization with bacterially expressed N, while not inducing protection directly, improved the induction of protection by a subsequent inoculation with inactivated IBV. In another study, two intramuscular immunizations of a plasmid expressing N induced protective immunity.

The basis of immunity to IBV is not well understood. Serum antibody levels do not correlate with protection, although local antibody is believed to play a role. Adoptive transfer of IBV-infection-induced αβ T cells bearing CD8 antigen protected chicks from challenge infection.

In conclusion, live attenuated IBV vaccines induce good, although short-lived, protection against homologous challenge, although a minority of individuals may respond poorly. Inactivated IBV vaccines are insufficiently efficacious when applied only once and in the absence of priming by live vaccine. Two applications of inactivated IBV are much more efficacious, although this is not a commercially viable proposition in the poultry industry. However, the cost and logistics of multiple application of a SARS inactivated vaccine would be more acceptable for the protection of human populations, especially if limited to targeted groups (e.g. health care workers and high-risk contacts). Application of a SARS vaccine is perhaps best limited to a minimal number of targeted individuals who can be monitored, as some vaccinated persons might, if infected by SARS coronavirus, become asymptomatic excretors of virus, thereby posing a risk to non-vaccinated people. Looking further into the future, the high efficacy of the fowl adenovirus vector expressing the IBV S1 subunit provides optimism for a live SARS vaccine, if that were deemed to be necessary, with the possibility of including the N protein gene.  相似文献   

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OBJECTIVE: To determine whether the routine examination of the newborn by a midwife compared with a junior paediatrician (SHO) affects maternal satisfaction with this examination. METHODS: Randomised controlled trial: 826 mother and baby pairs in a district general hospital in south east England were randomised to a paediatric SHO or a midwife for the routine newborn examination. Maternal satisfaction with the examination was analysed in relation to intervention group, process, and background variables. RESULTS: Some 81% of mothers reported that they were satisfied or very satisfied with the newborn examination. Mothers assigned to a midwife were more satisfied with the newborn examination (crude odds ratio (OR) 0.54 (95% confidence interval (CI) 0.39 to 0.75), p < 0.001). However, after provision of health education during the examination, continuity of care provided, and history of miscarriage had been controlled for, status of examiner was no longer related to maternal satisfaction (adjusted OR 0.82 (95% CI 0.57-1.20), NS). The discussion of healthcare issues by the examiner (adjusted OR 0.49 (95% CI 0.34 to 0.70), p < 0.001) and continuity of care (adjusted OR 0.43 (95% CI 0.23 to 0.81), p < 0.01) were both related to enhanced satisfaction, and history of miscarriage (adjusted OR 1.61 (1.08 to 2.40), p < 0.05) was associated with lower maternal satisfaction with the newborn examination. Midwives (61%) were more likely than SHOs (33%) to discuss healthcare issues, such as feeding, sleeping, and skin care. CONCLUSIONS: Mothers were more likely to be satisfied with the newborn examination by a midwife than an SHO because midwives were more likely to discuss healthcare issues during the examination and were able to provide continuity of care. However, midwife examinations according to exclusion criteria agreed with trial midwives excluded half of all newborns, and criteria may have to be reconsidered for practice implementation.  相似文献   
95.

Aims/hypothesis  

Subcutaneous immunisation with the 9–23 amino acid region of the insulin B chain (B:9-23) in incomplete Freund’s adjuvant (IFA) can protect the majority of 4- to 6-week-old prediabetic NOD mice and is currently in clinical trials. Here we analysed the effect of B:9-23/IFA immunisation at later stages of the disease and the underlying mechanisms.  相似文献   
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Perito ER, Glidden D, Roberts JP, Rosenthal P. Overweight and obesity in pediatric liver transplant recipients: Prevalence and predictors before and after transplant, United Network for Organ Sharing Data, 1987–2010.
Pediatr Transplantation 2012: 16: 41–49. © 2011 John Wiley & Sons A/S. Abstract: Obesity is extremely common in adult liver transplant recipients and healthy U.S. children. Little is known about the prevalence or risk factors for post‐transplant obesity in pediatric liver transplant recipients. UNOS data on all U.S. liver transplants 1987–2010 in children 6 months–20 yr at transplant were analyzed. Subjects were categorized as underweight, normal weight, overweight, or obese by CDC guidelines. Predictors of weight status at and after transplant were identified using multivariate logistic regression. Of 3043 children 6–24 months at transplant, 14% were overweight. Of 4658 subjects 2–20 yr at transplant, 16% were overweight and 13% obese. Children overweight/obese at transplant were more likely to be overweight/obese at one, two, and five yr after transplant in all age groups after adjusting for age, ethnicity, primary diagnosis, year of transplant, and transplant type. Weight status at transplant was not associated with overweight/obesity by 10 yr after transplant. The prevalence of post‐transplant obesity remained high in long‐term follow‐up, from 20% to 50% depending on age and weight status at transplant. Weight status at transplant is the strongest predictor of post‐transplant overweight/obesity. To optimize long‐term outcomes in pediatric liver transplant recipients, monitoring for obesity and its comorbidities is important.  相似文献   
98.
Reactive arthritis (ReA) induced by infection with several gram-negative bacteria is strongly associated with expression of the major histocompatibility complex class I molecule HLA-B27. It is thought that due to the intracellular lifestyle of ReA-inducing bacteria, bacterial fragments can be presented by HLA-B27. Cytotoxic T cells recognizing such bacterial peptides or other induced host peptides could cross-react with self peptides presented in the joints, giving rise to disease. Studies to analyze the B27 peptide repertoire in relation to infection were severely hampered, as complex peptide profiles obtained from separate infected and noninfected cell preparations had to be compared. For this study, we applied a new approach to examine the effect of Salmonella enterica serovar Typhimurium infection on the B27 peptide repertoire presented by the HLA-B*2704 subtype associated with disease. Firstly, we showed that both host cell and S. enterica serovar Typhimurium proteins can be tagged metabolically with stable-isotope-labeled arginine. We then designed experiments so that either the tagged endogenous or tagged bacterial B*2704-presented peptide repertoires from infected cells could be analyzed by mass spectrometry from single peptide preparations that included uninfected controls. Using this new approach, we found no evidence for significant changes in endogenous B*2704 peptide presentation after infection or for any S. enterica serovar Typhimurium-derived B27-bound peptide. In conclusion, the hypothesis that S. enterica serovar Typhimurium induces changes in B27 peptide presentation could not be supported.  相似文献   
99.
Completion of the human genome project is expected to lead to an increase in the number of individuals who participate in genetics research. The current informed consent process-developed prior to widespread genetics research-may not be sufficient to minimize the research risks that these individuals face. The current consent process focuses on informing individuals of the risks of research participation prior to their research enrollment. However, the risks of genetics research often are influenced by what subjects disclose to others after their research participation has ended. To assess whether the current consent process helps subjects remember the risks of future disclosures and, thereby, minimize the risks of genetics research, we interviewed 130 individuals who had previously participated in genetics research. Nineteen percent recalled that their samples would undergo genetic testing; 16% recalled that samples might be used for future research; 15% recalled that release of research records could affect their insurance status. These data suggest that current consent practices may not minimize the risks of genetics research. To address this concern, Institutional Review Boards and investigators should consider implementing supplemental mechanisms to help subjects remember when forgetting aspects of their research participation could place them at increased risk.  相似文献   
100.
Yersinia pestis, the causative agent of deadly plague, is considered a reemerging infectious disease and a significant biological terrorism threat. The present project focused on epidemiological investigation of the genetic variability of well-documented strains of Y. pestis from the United States by pulsed-field gel electrophoresis (PFGE) and restriction fragment length polymorphism (RFLP) analysis with insertion sequences IS100 and IS285 as probes. We examined 37 U.S. Y. pestis strains and isolates of a single ribotype, ribotype B, recovered between 1939 and 1998 from patients, animals, and fleas. Our results showed that all isolates had similar PFGE patterns, but minor differences such as missing, additional, and shifted bands were found among almost all strains if they came from different parent strains. The 37 strains and isolates were divided into 26 PFGE types. RFLP analysis with IS100 as a probe divided these strains and isolates into 16 types, with 43% belonging to IS100 type 1. Typing with IS285 as a probe was less specific and led to only four RFLP types, with 81% belonging to type 1. Similarity analysis with BioNumerics software showed that all strains shared >or=80, 86, and 91% similarities on dendrograms prepared from digitized PFGE, IS100 RFLP analysis, and IS285 RFLP analysis images, respectively. Our results demonstrate that PFGE offers an increased ability to discriminate between strains (Simpson's index of diversity, 0.98) and therefore can significantly improve epidemiological studies related to the origin of new plague isolates.  相似文献   
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