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Background

The complement system is one of the most potent weapons of innate immunity. It is not only a mechanism for direct protection against invading pathogens but it also interacts with the adaptive immunity to optimize the pathogen-specific humoral and cellular defense cascades in the body. Complement-mediated lysis of HIV is inefficient but the presence of HIV particles results in complement activation by the generation of many C3-fragments, such as C3dg and C3d. It has been demonstrated that activation of complement can enhance HIV infection through the binding of special complement receptor type 2 expression on the surface of mature B cells and follicular dendritic cells.

Presentation of the hypothesis

Previous studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that a new activator of complement, consisting of a target domain (C3-binding region of complement receptor type 2) linked to a complement-activating human IgG1 Fc domain (CR2-Fc), can target and amplify complement deposition on HIV virions and enhance the efficiency of HIV lysis.

Testing the hypothesis

Our hypothesis was tested using cell-free HIV-1 virions cultivatedin vitro and assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified CR2-Fc proteins. As a control group, viruses were incubated with normal human serum under the same conditions. Virus neutralization assays were used to estimate the degree of CR2-Fc-enhanced lysis of HIV compared to untreated virus.

Implications of the hypothesis

The targeted complement activator, CR2-Fc, can be used as a novel approach to HIV therapy by abrogating the complement-enhanced HIV infection of cells.  相似文献   

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A survey of medical staffing in 50 adult dialysis units in the United Kingdom in 1986 showed a wide range of patient to staff ratios or staffing score ratios. The total patient load (patients receiving haemodialysis in hospital and at home and those receiving continuous ambulatory peritoneal dialysis) varied from 12 to 270 per unit. Patients receiving acute haemodialysis or who had received a transplant were not included. The unit staffing score, on a weighted scale based on experience, varied from 6.0 to 40.5. Previous surveys have all been regionally or nationally based so criteria for assessing the adequacy of staffing in single units do not exist. This survey attempts to provide a guideline by describing the range of medical staffing compared with patient load in single dialysis units. No unit considered itself to be overstaffed, and several considered themselves to be greatly understaffed. Individual dialysis units should plead their own case in the light of their own circumstances and up to date information provided in nationwide staffing surveys such as this one.  相似文献   

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《BMJ (Clinical research ed.)》1973,1(5848):259-262
The efficacy of pertussis vaccines was investigated in 33 areas in the United Kingdom from November 1966 until April 1968 inclusive. Bordetella pertussis was isolated from 1,293 persons, but there were only six isolations of B. papapertussis. Among vaccinated contacts under 5 years in homes in which B. pertussis was isolated 52% developed paroxysmal cough. The corresponding attack rate among unvaccinated contacts was 69%. These findings suggest that much of the pertussis vaccine in use for five or six years before 1968 was not very effective. However, vaccine from one producer was more effective than vaccine from another. Of the cultures of B. pertussis identified 89% were serotype 1, 3 and only about 9% were serotype 1, 2, 3. Serotype 1, 2, 3 was isolated much more frequently from unvaccinated than from vaccinated children, but some cultures identified as type 1, 2, 3 were found on re-examination to contain colonies of type 1, 3. Virological investigations were made in some areas during the first year of the study. Of the wide variety of viruses identified adenovirus and parainfluenza virus were the most common groups. Virus isolation rates were similar in patients and symptomless contacts, but B. pertussis was isolated far more often from patients than from symptomless contacts. The evidence suggests that B. pertussis remained the major cause of whooping cough in the U.K.  相似文献   

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Darren Shickle 《Bioethics》1997,11(3&4):277-290
The Government in the UK is encouraging consumerism within health care and is requiring Health Authorities to consult with the public on prioritisation of resources. Public consultation within the National Health Service (NHS) has had limited success in the past. Many of the techniques used are flawed. Despite the limited scope of the public surveys conducted so far, a number of themes have emerged:
— a willingness to pay for experimental, 'high-tech' life-saving treatments rather than more cost-effective treatments which will improve quality of life, which are more likely to maximise utility from the scarce resources available;
— preference for treating the young rather than the old;
— preference for treating patients with dependants (e.g. spouse, children) rather than those who have none;
— a willingness to discriminate against those patients who were partially responsible for their illness due to choice of `unhealthy' lifestyle (e.g. smoking cigarettes, drinking excess alcohol).
These public preferences raise ethical problems. For example, is it just to spend more on heroic treatments which are likely to fail? Is there a right to health care irrespective of whether you have had 'a fair innings' or whether a patient is in part responsible for their illness due to an unhealthy lifestyle? If there are ethical concerns about these preferences, should health authorities consult with the public at all? Is human life and suffering incommensurable, and hence is it impossible to prioritise anyway? Some of the ethical consequences of using empirical data on public preferences are discussed.  相似文献   

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Blood units for transfusion are screened routinely in Ontario for the presence of hepatitis B antigen (HB-Ag) by counter-immunoelectrophoresis (CIEP). Since the radioimmunoassay (RIA) method is more sensitive for this purpose we used it to test blood units delivered to the hospital''s Renal Dialysis Unit in order to determine if HB-Ag-carrying blood donors were being missed by the less sensitive CIEP method.Out of the 606 blood units tested, eight were found to contain HB-Ag, an incidence of 13 out of 1000 donors. This finding indicates that the counter-immunoelectrophoresis method is insufficiently sensitive as a safe screening method for detection of hepatitis antigen.  相似文献   

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Serum samples from 214 blood donors in the United Kingdom who were carriers of hepatitis B surface antigen (HBsAg) were examined for hepatitis B virus deoxyribonucleic acid (DNA) by DNA:DNA hybridisation and for hepatitis B e antigen (HBeAg) and its antibody. One fifth of the donors carried infectious virus in their circulation. The presence of hepatitis B virus DNA correlated well with that of HBeAg, although hepatitis B virus DNA was found in five serum samples that were negative for HBeAg. It is concluded that analysis of serum samples for hepatitis B virus DNA by hybridisation should be the method of choice for determining whether carriers of HBsAg are infectious.  相似文献   

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