Low penetrance, broad resistance, and favorable outcome of interleukin 12 receptor beta1 deficiency: medical and immunological implications.

The clinical phenotype of interleukin 12 receptor beta1 chain (IL-12Rbeta1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rbeta1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin -BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rbeta1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most.

Diagnostic accuracy of a global cognitive screen for Maori and non-Maori octogenarians.

INTRODUCTION: We assessed the sensitivity and specificity of the Modified Mini-Mental State Examination (3MS) in predicting dementia and cognitive impairment in Maori (indigenous people of New Zealand) and non-Maori octogenarians. METHODS: A subsample of participants from Life and Living in Advanced Age: a Cohort Study in New Zealand were recruited to determine the 3MS diagnostic accuracy compared with the reference standard. RESULTS: Seventy-three participants (44% Maori) completed the 3MS and reference standard assessments. The 3MS demonstrated strong diagnostic accuracy to detect dementia with areas under the curve of 0.87 for Maori and 0.9 for non-Maori. Our cutoffs displayed ethnic variability and are approximately 5 points greater than those commonly applied. Cognitive impairment yielded low accuracy, and discriminatory power was not established. DISCUSSION: Cutoffs that are not age or ethnically appropriate may compromise the accuracy of cognitive screens. Consequently, older age and indigeneity increase the risk of mislabeled cognitive status.

Cellular composition of human glial cultures from adult biopsy brain tissue.

Microglia and astrocytes play vital roles in normal human brain function and in neurological disorders. To study their physiological and pathological roles it is desirable to establish in vitro systems that are derived from the adult human brain. Although several groups have successfully cultured cells from the human brain, the composition of these cultures remains controversial. Using morphological criteria, immunocytochemical analysis and a BrdU incorporation assay we demonstrate the presence of poorly proliferative microglia and astrocytes in cultures derived from epilepsy biopsy tissue. In addition, we characterized a third cell type as fibronectin and prolyl 4-hydroxylase immunopositive fibroblast-like cells, which are highly proliferative and become the predominant cell type after successive sub-culturing. Therefore, although cultures from adult human brain tissue provide an excellent resource for studying human glial cells, careful consideration must be given to their cellular composition when performing studies using these methods.

TBP, a polyglutamine tract containing protein, accumulates in Alzheimer's disease.

Alzheimer's disease (AD) is characterised by extra cellular beta-amyloid (betaA) deposition, Tau-containing neurofibrillary tangles (NFTs) and progressive cortical atrophy. Abnormal protein accumulation is also a common feature of other late onset neurodegenerative diseases, including the heritable polyglutamine (polyQ) disorders such as Huntington disease (HD) and the spinocerebellar ataxias (SCAs). One of this family of disorders, SCA17, is caused by an expansion of a polymorphic polyQ repeat in TATA binding protein (TBP), an essential transcription factor. Surprisingly, the wild type TBP repeat length ranges from 25 to 42, and in Caucasian populations the most common allele is 38, a size large enough to cause HD if within the huntingtin protein. Wild type length TBP accumulates in HD and in at least some of the SCAs, and consequently we hypothesised that it may contribute to AD. Here we provide evidence that TBP accumulates in AD brain, localising to neurofibrillary tangle structures. A proportion of TBP present in AD brain is insoluble; a signature of the polyQ diseases. TBP is present differentially between patients and its amount and distribution is not directly proportional to that of Tau or beta-amyloid positive structures. We present this as evidence for the hypothesis that the accumulation or misfolding of this polyQ containing protein may be a contributing factor in Alzheimer's disease.

Validity of self-reported health plan information in a population-based health survey.

OBJECTIVE: To validate information on private health insurance coverage in a population-based study. METHODS: Respondents to the Massachusetts Behavioral Risk Factor Surveillance System were asked the name of their health plan company (affiliation) and specific brand of insurance (product), the duration in which they belonged to the plan, and demographic and health-related data. Information on plan affiliation and product was used to classify individuals on type of coverage. At the end of the survey, respondents with health insurance were asked to retrieve their health plan cards, and to read detailed information from the cards. Self-reported data were compared with information from the cards. RESULTS: Self-reported information on health plan affiliation agreed with plan cards for 93 percent of individuals, while agreement was 79 percent for health plan product. Among health maintenance organization (HMO) participants, 93 percent correctly reported being in an HMO (sensitivity), whereas 76 percent of respondents in a non-HMO plan correctly self-reported (specificity). Individuals with higher levels of income, those with a primary care doctor, and those in a health plan for at least 1 year had higher agreement. Higher validity was associated with poor physical health and recent cancer screening. CONCLUSIONS: Self-reported data on health plan affiliation and product have good validity in a population-based sample of adults. While agreement differs according to specific respondent characteristics, these differences do not appear substantial.