Nancy Miller

Brain function, intellectual impairment and education in the aged.

In assessing behavioral problems of the elderly there is a need for procedures which reliably indicate the presence and extent of impaired brain function. In this study, the relation of two mental status measures [the Mental Status Questionnaire (MSQ) and the Face‐Hand test] to intellectual performance and education was evaluated. The sample consisted of 153 consecutive inpatients and outpatients referred to a gerontology clinic. Intellectual performance was assessed with 8 tests of learning and memory, such as Paired Associates and Babcock Story Recall. The findings indicate that positive ratings for impaired brain function on either mental status test were related to lower intellectual performance at each of three levels of education — grade school, high school, and college. Subjects with more education and mental status scores indicating mild impairment performed better on intellectual tests than did less educated persons with no brain dysfunction, but they showed significant deficits compared to other subjects with similar education and intact brain function. Larger intellectual deficits were found when the patient made more test errors and when both tests gave positive ratings. These results confirm the importance of the MSQ and Face‐Hand tests as screening devices for the intellectual deficits associated with impaired brain function in a clinically heterogeneous population.

A Gag-Pol/Env-Rev SIV239 DNA vaccine improves CD4 counts, and reduce viral loads after pathogenic intrarectal SIVmac251 challenge in Rhesus Macaques

DNA vaccines are an important vaccine approach for many infectious diseases including human immunodeficiency virus (HIV). Recently, there have been exciting results reported for plasmid vaccination in pathogenic SHIV model systems. In these studies, plasmid vaccines supplemented by IL-2 Ig cytokine gene adjuvants or boosted by recombinant MVA vectors expressing relevant SIV and HIV antigens prevented CD4(+) T-cell loss and lowered viral loads following pathogenic challenge. However, similar results have not been reported in a direct pathogenic macaque challenge model. Here we report on a study of the ability of a multiplasmid SIV DNA vaccine in a pathogenic SIV251 rhesus mucosal challenge study. We observed that pGag/Pol+pEnv/Rev plasmid vaccines could not prevent SIV infection; however, vaccinated animals exhibited significant improvement in control of viral challenge compared to control animals. Furthermore, vaccinated animals exhibited protection against CD4(+) T-cell loss.

Assessment of Altered Brain Function in the Aged

Numerous behavioral procedures have been described in the literature which are intended to evaluate the presence and/or degree of altered brain function. Determination of the efficacy of these procedures is difficult enough in general, but becomes considerably more complicated when applied to the aged in particular. The purpose of this chapter is to consider some of the clinical issues including: the meaning of “organic brain dysfunction” that the behavioral procedures are supposed to measure, the problems of false positives and negatives, the circumstances under which the clinical examination is likely to occur, and the common problems of differential diagnosis encountered. There will be a review of the psychometric and clinical evaluation procedures commonly employed and, finally, measures which are most likely to be clinically useful will be recommended and described in detail.

Knowledge-based indexing of the medical literature: the indexing aid project

This article describes the Indexing Aid Project for conducting research in the areas of knowledge representation and indexing for information retrieval in order to develop interactive knowledge-based systems for computer-assisted indexing of the periodical medical literature. The system uses an experimental frame-based knowledge representation language, FrameKit, implemented in Franz Lisp. The initial prototype is designed to interact with trained MEDLINE indexers who will be prompted to enter subject terms as slot values in filling in document-specific frame data structures that are derived from the knowledge-base frames. In addition, the automatic application of rules associated with the knowledge-base frames produces a set of Medical Subject Heading (MeSH) keyword indices to the document. Important features of the system are representation of explicit relationships through slots which express the relations; slot values, restrictions, and rules made available by inheritance through “is-a” hierarchies; slot values denoted by functions that retrieve values from other slots; and restrictions on slot values displayable during data entry.

Quantitative and functional analyses of spleen and in situ islet immune cells before and after diabetes onset in the nod mouse

Cytofluorometric analysis using specific monoclonal antibodies directed against the T cell antigens Thy-1.2, CD4, CD8, CD4V beta(8.1 + 8.2 + 8.3), and the antigen Mac-1 expressed by mature macrophages and NK cells were used to characterize and quantify the phenotypes of (1) unfractionated and Percoll gradient fractionated in situ islet immune cells isolated from prediabetic and diabetic female NOD mouse spleens. We found in prediabetic female mice that the majority (approximately 70%) of the in situ islet immune cells were Thy-1.2 positive T cells. CD4 positive T cells (approximately 40%) were the most abundant phenotype together with double negative T cells (approximately 20%). The percentage of CD8 positive T cells were approximately 10%, and only approximately 4% of the immune cells were Mac-1 positive. The percentages of CD4V beta (8.1 + 8.2 + 8.3) positive and double negative T cells in diabetic spleens were significantly higher in comparison to prediabetic spleens. In C57B1/6J control nondiabetic mice the percentage of double negative T cells in the spleens was significantly 4-fold lower when compared to diabetic NOD spleens. The specific cytolytic activity mediated by in situ islet immune cells against 51Cr-labeled dispersed syngeneic single-cell islet cells at an effector to target ratio of 20 was twenty- to thirty-fold higher than that mediated by prediabetic splenic lymphoid cells. It is concluded that prediabetic NOD mouse in situ islet immune cells are mostly CD4 positive and double negative T cells, and that CD4 and CD8 positive T cells in the intra-islet infiltrate warrants further evaluation as potential effector T cells in target beta-cell destruction.

Adoptive Immunotherapy of Diabetes in Autologous Nonobese Diabetic Mice With Lymphoid Cells Ex Vivo Exposed to Cyclosporin Plus Interleukin 2

Between 12 and 26 wk of age, ∼80% of female nonobese diabetic (NOD) mice from the inbred Sansum colony develop lymphocytic insulitis and become overtly diabetic. The disease in this animal model is similar to human insulin-dependent diabetes mellitus (IDDM) in both genetics and autoimmune pathogenesis. Cyclosporin A (CsA) has been used for immunosuppression in IDDM of recent onset in humans but has several limiting side effects. Therefore, a different regimen for CsA immunosuppression was investigated. Autologous splenic lymphoid cells from 12-wk-old not-yet-diabetic female NOD mice were cultured for 72 h with CsA plus interleukin 2 (IL-2) before reinfusion into the animal from which they were isolated. After this treatment, only 2 (18%) of 11 mice became overtly diabetic during an observation period of 19 wk, while 18 (86%) of 21 age-matched control mice developed diabetes during the same observation period (P < .001). These data suggest an ex vivo preferential IL-2 activation of specific suppressor cells for the autoimmune process with CsA blockade of cytolytic/helper activities. Because the in vivo concentrations of CsA with this procedure would be negligible, these findings have implications for the potential nontoxic use of CsA in human protocols as well.