SOURCES AND EFFECTS OF IONIZING RADIATION : United Nations Scientific Committee on the Effects of Atomic Radiation UNSCEAR 2000 Report to the General Assembly, with Scientific Annexes

Endophenotypes, measurable components unseen by the unaided eye along the pathway between disease and distal genotype, have emerged as an important concept in the study of complex neuropsychiatric diseases. An endophenotype may be neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, or neuropsychological (including configured self-report data) in nature. Endophenotypes represent simpler clues to genetic underpinnings than the disease syndrome itself, promoting the view that psychiatric diagnoses can be decomposed or deconstructed, which can result in more straightforward-and successful-genetic analysis. However, to be most useful, endophenotypes for psychiatric disorders must meet certain criteria, including association with a candidate gene or gene region, heritability that is inferred from relative risk for the disorder in relatives, and disease association parameters. In addition to furthering genetic analysis, endophenotypes can clarify classification and diagnosis and foster the development of animal models. The authors discuss the etymology and strategy behind the use of endophenotypes in neuropsychiatric research and, more generally, in research on other diseases with complex genetics.

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The Endophenotype Concept in Psychiatry: Etymology and Strategic Intentions

Background The extent to which renal allotransplantation — as compared with long-term dialysis — improves survival among patients with end-stage renal disease is controversial, because those selected for transplantation may have a lower base-line risk of death. Methods In an attempt to distinguish the effects of patient selection from those of transplantation itself, we conducted a longitudinal study of mortality in 228,552 patients who were receiving long-term dialysis for end-stage renal disease. Of these patients, 46,164 were placed on a waiting list for transplantation, 23,275 of whom received a first cadaveric transplant between 1991 and 1997. The relative risk of death and survival were assessed with time-dependent nonproportional-hazards analysis, with adjustment for age, race, sex, cause of end-stage renal disease, geographic region, time from first treatment for end-stage renal disease to placement on the waiting list, and year of initial placement on the list. Results Among the various subgroups...

https://www.nejm.org/doi/pdf/10.1056/NEJM199912023412303

Comparison of Mortality in All Patients on Dialysis, Patients on Dialysis Awaiting Transplantation, and Recipients of a First Cadaveric Transplant

NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Sixty-third Session, Supplement No. 46. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those that were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where this was possible and appropriate, to reflect political changes. Scientific Annexes Annex A. Medical radiation exposures Annex B. Exposures of the public and workers from various sources of radiation INTROdUCTION 1. In the course of the research and development for and the application of atomic energy and nuclear technologies, a number of radiation accidents have occurred. Some of these accidents have resulted in significant health effects and occasionally in fatal outcomes. The application of technologies that make use of radiation is increasingly widespread around the world. Millions of people have occupations related to the use of radiation, and hundreds of millions of individuals benefit from these uses. Facilities using intense radiation sources for energy production and for purposes such as radiotherapy, sterilization of products, preservation of foodstuffs and gamma radiography require special care in the design and operation of equipment to avoid radiation injury to workers or to the public. Experience has shown that such technology is generally used safely, but on occasion controls have been circumvented and serious radiation accidents have ensued. 2. Reviews of radiation exposures from accidents have been presented in previous UNSCEAR reports. The last report containing an exclusive chapter on exposures from accidents was the UNSCEAR 1993 Report [U6]. 3. This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices. Its conclusions are to be seen in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation. 4. The Committee's evaluations of public, occupational and medical diagnostic exposures are mostly concerned with chronic exposures of …

sources and effects of ionizing radiation

Multiple sclerosis is primarily an inflammatory disorder of the brain and spinal cord in which focal lymphocytic infiltration leads to damage of myelin and axons. Initially, inflammation is transient and remyelination occurs but is not durable. Hence, the early course of disease is characterised by episodes of neurological dysfunction that usually recover. However, over time the pathological changes become dominated by widespread microglial activation associated with extensive and chronic neurodegeneration, the clinical correlate of which is progressive accumulation of disability. Paraclinical investigations show abnormalities that indicate the distribution of inflammatory lesions and axonal loss (MRI); interference of conduction in previously myelinated pathways (evoked electrophysiological potentials); and intrathecal synthesis of oligoclonal antibody (examination by lumbar puncture of the cerebrospinal fluid). Multiple sclerosis is triggered by environmental factors in individuals with complex genetic-risk profiles. Licensed disease modifying agents reduce the frequency of new episodes but do not reverse fixed deficits and have questionable effects on the long-term accumulation of disability and disease progression. We anticipate that future studies in multiple sclerosis will provide a new taxonomy on the basis of mechanisms rather than clinical empiricism, and so inform strategies for improved treatment at all stages of the disease. 

Multiple sclerosis

61-P: HLA class I epitopes: 103 total epitopes to-date including the C locus

In this preliminary study the phenotypic distribution of HLA and DRw antigens was investigated in patients with recurrent herpes progenitalis. Ninety-three white men between the ages of 20 and 53 years, with at least a 2-year history of recurrent herpes progenitalis infection, and 558 age-matched white men from the same area of Los Angeles were studied by means of a microcytotoxicity assay. Statistical analysis of data indicated that there is no increased incidence of any HLA antigen. The B cell antigen DRw7 is present in 37% of the patients and 22% of controls, with a p value of 0.009 and a relative risk of 2.1. These results suggest that there may be genetic and immunologic factors that tend to predispose certain individuals to the development of recurrent herpes progenitalis when they are exposed to the virus. (J AM ACAD DERMATOL 6:898-901, 1982.)

https://www.jaad.org/article/S0190-9622(82)70079-9/pdf

A study of HLA and DRw antigens in recurrent herpes progenitalis (HSV-2) infection severe

Serology of HLA.

72-P Pre-transplant HLA-DSA that persist post-transplant predict increased risk of antibody-mediated rejection and graft loss in renal transplantation

We have used information available in the UCLA International Transplant Registry to study the effect of HLA antigens on graft survival outcome. All results showed that of all antigens tested, the presence of DR1 in the recipient was associated with the highest graft survival rate. There was a positive matching effect for most DR antigens that were either presumed homozygous or heterozygous in the recipient. A regression analysis not only confirmed the association of DR1 and low immune response, but also suggested a greater importance of the DR rather than A or B locus to graft survival rates. Recipients with DR1,5 had the highest survival rates when DR1 was compared with other DR antigens and the heterozygous combinations of the two groups. This suggests that presence of heterozygous DR antigens may have combined effects on graft survival.

The Effect of Individual HLA Antigens on Graft Survival Rates in Kidney Transplant Patients

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