The rich in India. US research has made Urvashi Butalia think about how rich people behave in Delhi. My office is in an urban village in the middle of Delhi. Introduction. Variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom and some other countries 1 2 was caused by an exposure of the population to bovine spongiform encephalopathy (BSE) tedxamman.infoon: Rockville Pike, Bethesda, MD.
On a technical aspect, our study revealed a performance difference between the antibodies used, whereby ICSM35 had a higher signal to noise ratio than either KG9, 12F10, or 3F4.
This is in contrast with previous studies where 3F4 and KG9 were used. The appendix biopsy samples were material from surgery, usually rapidly and short term fixed in formalin and not treated with formic acid. It is possible that ICSM35 was more sensitive at detecting abnormal PrP in such biopsy samples and that the other three antibodies benefit from formic acid treatment after formalin fixation, as suggested in figure 1 E, J, O, T. Importantly, all four antibodies detected the same cell type in immunolabelled follicles of positive appendix samples.
Several studies have validated immunohistochemistry in combination with appropriate retrieval techniques as an adequate tool to detect abnormal PrP and underpin the validity and reliability of previous studies and the present study to detect abnormal PrP in archival material, 22 23 despite the unavailability of antibodies specific for abnormal PrP and suitable for formalin fixed, paraffin embedded material.
Importantly, these studies also concluded that lymphoreticular accumulation of abnormal PrP is a specific feature of vCJD in prion diseases in humans. For several reasons, immunohistochemically detected positivity in appendixes may underestimate the prevalence of abnormal PrP.
Firstly, it is assumed that tissue in an appendix block is adequately represented by the two adjacent sections that were screened. Although under-sampling would be a problem only in those appendixes that contained positive follicular dendritic cells in one or a few follicles, such biological variation could cause our method to have reduced sensitivity and lead to an underestimate of the prevalence of abnormal PrP.
Animal pathogenesis studies suggest that at early stages of the incubation period the number of positive follicles is low and increases with incubation time. Thirdly, we confirmed by using CD21 immunostaining for follicular dendritic cell that inflammation destroys these cells, hence reducing the number of potentially positive samples fig 1.
Fourthly, as with the first appendix survey, a limitation of the second survey for estimating the prevalence of asymptomatic infection and predicting future numbers of vCJD cases is that it is not known at what stage during the incubation period abnormal PrP can be detected in lymphoid tissue.
To date the discrepancy is growing between the prevalence of vCJD prions observed in the exposed population and the relatively small number of patients who have developed vCJD, whatever the true sensitivity and specificity of prion specific immunohistochemistry in appendixes.
The number of patients with clinically manifest vCJD cases at June is well below the number suggested by the prevalence of abnormal prion, even for those who are only methionine homozygous at PRNP codon an estimated cases. Nevertheless, these data are in keeping with recent animal experiments, which suggest that the human transmission barrier for bovine spongiform encephalopathy BSE may be high for clinical disease but substantially lower for peripheral lymphoreticular infection.
Therefore, the prevalence data raise several important issues. Firstly, it is not known whether hosts who are methionine-valine heterozygous or valine homozygous and carry immunopositive lymphoreticular tissues are protected from developing vCJD or if they will eventually develop clinical prion disease, and if so how prolonged the incubation period would be. Secondly, it is unclear the extent to which the risk of developing vCJD in someone who is methionine homozygous decreases with age at exposure and whether this decrease is so great that a perpetual asymptomatic carrier state is the result.
Thirdly, it is not known whether carriers pose a risk of transmitting the disease through surgical procedures 27 or through blood and other tissue donation. Finally, it is not known whether host carriers who are methionine-valine heterozygous and valine homozygous and develop clinical prion disease will present with clinical signs of vCJD with the PrP glycotype corresponding to type 4 2 28 also designated type 2b The PrP glycotype is a biochemical signature, determined by the glycosylation of specific sites of the PrP molecule which distinguishes sporadic and variant CJD.
Data from blood transmission studies in sheep suggest that blood infectivity is present early in the incubation period, whatever the primary route of infection. Instead, a larger number of future cases may occur as a result of secondary iatrogenic transmission in all genotypes, and should this secondary epidemic arise, it would do so over decades.
Before concluding that the clinical course of BSE related abnormal PrP in humans must differ from that in sheep, it would be prudent to measure the prevalence of abnormal PrP in human blood.
As soon as a satisfactory human blood screening test becomes available in a scalable format, such an unlinked anonymous survey should be undertaken. Meanwhile, although the discrepancy between prevalence of abnormal PrP in appendixes and observed cases of vCJD as a result of blood transmission suggests that the risks of transmission of vCJD by blood transfusion are low, it is unclear how many blood recipients may have subclinical disease and if their life expectancy is shorter than the incubation time.
Therefore it is essential to continue research into tests to detect abnormal PrP in blood. The second appendix survey has provided the most robust measure of abnormal prion prevalence to date, and has shown a wider birth cohort and all genotypes to be affected. Interpretation of these findings will be aided by a further survey, already begun, of appendix specimens surgically removed before the BSE epizootic, in the mid to late s, to inform about prevalence in the absence of dietary exposure.
We thank Joanne Kilkenny and Jessica Broni University College London Institute of Neurology and Linda Powell, Sarah Marsh, and the Pathology Unit histology team Animal Health and Veterinary Laboratories Agency for histological assistance; Diane Ritchie and Linda McCardle National CJD Research and Surveillance Unit for their expert assistance in the staining and assessment of sections for review; Phil Minor who chaired the group advising the PHE on laboratory practice in relation to large scale abnormal prion surveys and who chaired the consensus meetings of histopathologists involved in this survey; and the participating hospitals for providing us with archival histological samples for list of hospitals see supplementary table 4.
All authors, external and internal, had full access to all of the data including statistical reports and tables in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis.
NG and SB gave final approval of the version to be published and are the guarantors. The views expressed are those of the authors and not necessarily those of the UK Department of Health. None of the authors has a relationship with any company that might have an interest in the submitted work in the previous three years; their spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and none of the authors has non-financial interests that may be relevant to the submitted work.
As the residual tissue specimens were screened using the unlinked anonymous technique and ethical approval was obtained, the consent of the patients from whom the tissues originated was not required. A full dataset and technical appendix is available with open access in the supplementary material.
This includes digital histology images that can be accessed on request from the corresponding author at ku. National Center for Biotechnology Information , U.
Journal List BMJ v. Published online Oct O Noel Gill , head of department , 1 Yvonne Spencer , head of pathology , 2 Angela Richard-Loendt , senior research histologist , 3 Carole Kelly , senior CJD scientist , 1 Reza Dabaghian , senior scientific and technical manager , 4 Lynnette Boyes , histologist , 3 Jacqueline Linehan , senior research histologist , 5 Marion Simmons , veterinary research pathologist, head of EU Reference Laboratory for TSE , 2 Paul Webb , pathology research scientist , 2 Peter Bellerby , pathology research scientist , 2 Nick Andrews , senior statistician , 1 David A Hilton , consultant neuropathologist , 6 James W Ironside , professor of clinical neuropathology , 7 Jon Beck , research scientist , 5 Mark Poulter , research scientist , 5 Simon Mead , reader in neurology, consultant neurologist , 5 and Sebastian Brandner , professor of neuropathology, honorary consultant neuropathologist 3.
Author information Article notes Copyright and License information Disclaimer. Accepted Aug This article has been cited by other articles in PMC. Associated Data Supplementary Materials Supplementary information, tables, and figure captions.
Description of procedure for processing blocks. Abstract Objectives To carry out a further survey of archived appendix samples to understand better the differences between existing estimates of the prevalence of subclinical infection with prions after the bovine spongiform encephalopathy epizootic and to see whether a broader birth cohort was affected, and to understand better the implications for the management of blood and blood products and for the handling of surgical instruments.
Open in a separate window. Preparation of sections and immunohistochemical detection of abnormal PrP From each paraffin block we cut a primary set of three sections. Determination of PRNP codon genotype We determined the codon genotype of positive samples and a selection of others using allele discrimination with minor groove binding probes.
Detection of abnormal PrP in appendix samples and distribution of PRNP codon genotypes The survey included appendixes from operations conducted between and Difference between antibodies used in this study Strong labelling was usually produced by antiPrP antibody ICSM35 fig 2 A, B , whereas antiPrP antibody KG9 generally showed weaker immunoreactivity in the same follicles on immediately adjacent sections fig 2 F, G , in contrast with sporadic Creutzfeldt-Jakob disease brain sections, where both antibodies showed identical signals fig 2 C, D, H, I.
Follicular dendritic cells degradation in inflamed appendixes Robust CD21 immunolabelling of follicular dendritic cell was seen in all follicles in appendixes with no or minimal granulocyte infiltration see supplementary fig 1 A-C , whereas fewer CD21 positive follicular dendritic cells were seen in moderately inflamed appendixes see supplementary fig 1 D-F and none in severely inflamed appendixes, where follicles were overrun by inflammatory cells see supplementary fig 1 G-I.
Genotypes of positive appendix samples A striking finding of the first appendix survey was the presence of the valine homozygous genotype at PRNP codon 17 in two of the three positive samples. Technical aspects of the antibodies On a technical aspect, our study revealed a performance difference between the antibodies used, whereby ICSM35 had a higher signal to noise ratio than either KG9, 12F10, or 3F4. Sensitivity of the tests For several reasons, immunohistochemically detected positivity in appendixes may underestimate the prevalence of abnormal PrP.
Discrepancy between prevalence estimates and vCJD incidence To date the discrepancy is growing between the prevalence of vCJD prions observed in the exposed population and the relatively small number of patients who have developed vCJD, whatever the true sensitivity and specificity of prion specific immunohistochemistry in appendixes.
Conclusions The second appendix survey has provided the most robust measure of abnormal prion prevalence to date, and has shown a wider birth cohort and all genotypes to be affected.
What is already known on this topic Widespread exposure of the UK population to bovine spongiform encephalopathy prions led to the emergence of variant Creutzfeldt-Jakob disease vCJD. Refrain from posting comments that are obscene, defamatory or inflammatory, and do not indulge in personal attacks, name calling or inciting hatred against any community.
Help us delete comments that do not follow these guidelines by marking them offensive. Let's work together to keep the conversation civil. Infrastructure along border with China to be enhanced. Close on the heels of Doklam standoff, the defence ministry has decided to significantly enhance infrastructure along the nearly 4, km-long Sino- India border including around the areas of dispute.
Close on the heels of Doklam standoff, the defence ministry has decided to significantly enhance infrastructure along the nearly 4, km-long Sino-India border including around the areas of dispute.
The decision was taken at the Army's commanders conference which extensively deliberated on the Doklam face off with China besides analysing all possible security challenges on the northern border, official sources said.
Director General Staff Duties Lt. Vijay Singh, briefing on the outcome of the conclave which was attended by top defence ministry officials among others, said it was decided that there would be considerable "heft" towards road construction activities in the northern sector.
He said the commanders also examined organisational changes of some of the formations to enhance existing capability, indicating that the Army leadership was looking at bolstering its current operational preparedness to meet any contingencies.
In another test, when poorer people could give away points which represented money , they gave away more points than richer people. Keltner also studied the vagus nerve. This nerve helps the brain with emotions. When people are shown pictures of starving children, for example, their vagus nerve becomes more active. Keltner has found that this nerve is more active in poorer people. One of his students, Jennifer Stellar, did a similar experiment using heart rate.
The heart becomes slower when people feel compassion. The heart rates of the richest students did not change when they looked at pictures of children with cancer, but the heart rates of poorer students did change. Using quizzes, online games, questionnaires and other research, Piff also found that richer people are less ethical, more selfish, more insular and have less compassion.
One experiment put people in a room with a bowl of sweets for children. The rich people, were the most likely to take the sweets. Another experiment showed that rich people were three times more likely to cheat than poorer people. In another study, Piff and his researchers spent three months observing drivers at a busy road junction.
They gave cars a grade, from one to five, with five the most expensive. They found that drivers of grade-five cars were the most likely to drive badly, driving out in front of others. Piff then did an experiment to test how drivers think about people crossing roads. A researcher walked onto a zebra crossing as a car came along. Can the rich save themselves? We need more studies to show what happens if they give away their money.
Rich people sometimes try to look moral. Recently, three poor Dalit boys started a small fire by mistake in a local community centre where they worked. Their local community leader asked the manager of the centre not to punish them. But the manager said: They were probably the only people in their families with a job. In the US, the research shows that richer people learn how to take.
If we talk about money, not sweets, we see this a lot in India. Often, money for development programmes for the poor, is taken by the rich. Land that belongs to the poor is taken to build factories the Nano plant, for example without paying any compensation. Why do people who have so much want more? Maybe, soon, people in developing countries will start to look for answers to these questions. Urvashi Butalia is a feminist and historian.
She started the publishing house Zubaan in
Es erfordert eine erste Investition von Manhattan - Folge 5.
Die erste und offensichtlichste Auswirkung ist der Anreiz zu investieren. PLoS One ; 5: