Much evidence indicates that abnormal processing and extracellular deposition of amyloid-beta peptide (A beta), a proteolytic derivative of the beta-amyloid precursor protein (betaAPP), is central to the pathogenesis of Alzheimer's disease (reviewed in ref. 1). In the PDAPP transgenic mouse model of Alzheimer's disease, immunization with A beta causes a marked reduction in burden of the brain amyloid. Evidence that A beta immunization also reduces cognitive dysfunction in murine models of Alzheimer's disease would support the hypothesis that abnormal A beta processing is essential to the pathogenesis of Alzheimer's disease, and would encourage the development of other strategies directed at the 'amyloid cascade'. Here we show that A beta immunization reduces both deposition of cerebral fibrillar A beta and cognitive dysfunction in the TgCRND8 murine model of Alzheimer's disease without, however, altering total levels of A beta in the brain. This implies that either a approximately 50% reduction in dense-cored A beta plaques is sufficient to affect cognition, or that vaccination may modulate the activity/abundance of a small subpopulation of especially toxic A beta species.

Alzheimer Disease↗

PubMedDate not supplied

Inconsistency of fetal trophoblast cells in first trimester maternal peripheral blood prevents non-invasive fetal testing using this cell target.

We have investigated whether maternal peripheral blood from the first trimester of pregnancy is a reliable source of identifiable trophoblast cells. The cells were enriched from 30 ml of venous blood, with multiple antibodies shown previously to enrich trophoblasts and a new cocktail based on known trophoblast surface features. Three different magnetic solid phases were tested to enrich trophoblasts, and both positive and negative cell enrichment strategies were examined. The cells were identified as trophoblast by morphology coupled with immunocytochemistry to co-localize cytokeratin with one of three IGF-II, PAI-1 or hPLH proteins or by in-situ hybridization with a mixture of 50 oligos directed to eight different expressed genes, alpha-HCG, IGF-II, PAI-1, HASH2, hPLH, p57(KIP2), PP5, H-19. While these tools worked beautifully in chorionic villi cell/sprout preparations and tissue sections, we could not detect and identify any trophoblasts in maternal peripheral blood even if the maternal peripheral blood was drawn 5-20 min following termination of pregnancy or from individuals maintaining the pregnancy. Based on our own experience and that of some reports in the literature, trophoblasts do not appear to be a viable candidate for fetal screening using maternal peripheral blood as the source. It is important to note that while trophoblast deportation is a biological phenomenon that has been described repeatable, they do not provide a means to perform prenatal genetic diagnosis.

Antibodies↗

PubMedDate not supplied

Enrichment and identification of fetal trophoblast cells from first trimester maternal cervical lavage and uterine blood specimens.

First trimester prenatal diagnosis of fetal aneuploidies is an active area of research despite years of disappointing data employing maternal peripheral blood samples. To remedy this situation we have investigated other first trimester maternal specimens attempting to find a consistent fetal cell source. Using our previously established positive enrichment procedure along with a commercially available depletion method, fetal trophoblast cells were identified employing immunocytochemistry using an antibody cocktail or by using mRNA in-situ hybridization employing a cocktail of trophoblast specific probes. Fetal origin of positively identified cells was verified using interphase fluorescent in-situ hybridization (FISH) for X and Y-chromosomes. Artificial model systems were established that indicated yields of trophoblast cells and allowed the enrichment procedure to be optimized for minimal losses from maternal specimens. We demonstrate herein that blood drawn from maternal vessels near the placental implantation site to be the most consistent source of fetal cells from any first trimester maternal specimen described to date. In addition, a high yield of multinucleated syncytiotrophoblast cells was obtained using a cell depletion strategy to enrich the target cells. The safety of the procedure or even the clinical utility of blood drawn from maternal vessels near the placental implantation site is yet to be demonstrated.

Cell Separation↗

PubMedDate not supplied

Reliability and validity of the Frail Elderly Functional Assessment questionnaire.

Measuring functional activity for elderly at very low functional levels remains a challenge because many functional instruments have not been standardized in a frail elderly population. The Frail Elderly Functional Assessment questionnaire (FEFA) is a 19-item, interviewer-administered questionnaire designed to assess function in frail elderly at a very low activity level. The purpose of this study was to determine the reliability and validity of this instrument in a frail elderly population. Two groups of subjects over 65 yr old were selected to test the reliability and validity of this questionnaire. Test-retest reliability was determined by correlating the responses of 29 homebound (including nursing home-bound) subjects who answered the questionnaire on two occasions 2 wk apart. To assess the validity of the FEFA, the questionnaire was administered to 23 frail, homebound (including nursing home-bound) elderly subjects who had a Mini-Mental State Examination score of > or = 18. Validity was determined by correlating patient responses to direct observations by the investigators of tasks addressed in the questionnaire. Correlation was also determined against the Katz's Activity of Daily Living index, Lawton's Instrumental Activity of Daily Living index, and the Barthel index. The reliability coefficient was 0.82. Correlation between the FEFA questionnaire and direct observation of questionnaire task performance was 0.90. Construct validity against the Katz's Activity of Daily Living, Lawton's Instrumental Activity of Daily Living, and the Barthel index showed correlations of 0.86, 0.67 and 0.91, respectively. Initial data indicate that the FEFA is a valid and reliable instrument that may be useful in assessing function in frail elderly people.

Activities of Daily Living↗

PubMedDate not supplied

Problems of care in a private nursing home.

To assess problems of care in a private nursing home an observational study was carried out over two months, during which a research nurse worked as a member of the staff in a home caring for 25 patients aged 62-90. During the second month a consultant physician visited the home weekly to hold case conferences and assess each patient's functional ability and drug regimen. Various problems in medical, nursing, and bureaucratic matters were identified--for example, staff failed to understand the appropriate response to various medical symptoms; no clear policy existed for managing pressure sores; and one patient's anticoagulant state could not be assessed when industrial action meant that transport to take him to hospital was not available--and several changes in drug treatments were recommended. The problems that were identified were mainly due to poor communication between the home and general practitioners and hospitals and to the lack of guidance policy on common issues that arise in long term care. Such a policy could be produced by health authority staff, general practitioners, and representatives of nursing homes.

Aged↗

PubMedDate not supplied

The adherent gastric antral and duodenal mucus gel layer thins with advancing age in subjects infected with Helicobacter pylori.

BACKGROUND: Peptic ulceration and Helicobacter pylori infection increase with advancing age. In the upper gastro-intestinal tract the first line of mucosal defence is the adherent mucus gel layer. OBJECTIVE: We have examined, using a novel histological fixation technique, the thickness of the adherent mucus gel layer (1) in the gastric antrum and (2) in the duodenum in relation to advancing age and H. pylori status. METHODS: The subjects had macroscopically normal stomach and duodenum at endoscopy. Measurement of the gastric antral mucus thickness was carried out on four antral biopsy specimens from within 2 cm of the pylorus (H. pylori positive n = 25, negative n = 21). The duodenal mucus thickness (D1) was measured from two biopsy specimens (H. pylori positive n = 7, negative n = 13). All specimens were snap frozen and cryostat sections stained using a modified PAS/AB stain. RESULTS: In all sections the mucus layer was continuous. In both duodenum and gastric antrum, the mucus thickness was not significantly different between H. pylori positive and H. pylori negative age-matched samples. In duodenum and gastric antrum from H. pylori negative subjects, there was no correlation between mucus thickness and age. However, in H. pylori positive subjects, there was a significant thinning of the adherent gastric antral mucus gel layer (p = 0.005, r = -0.54) and the duodenal mucus thickness (p<0.001, r = -0.99) with advancing age. CONCLUSION: This study shows a significant thinning of the adherent mucus gel layer in H. pylori positive individuals, as stomach and duodenum age. In those without H. pylori, the mucus gel thickness is preserved in stomach and duodenum.

Aged↗

PubMedDate not supplied

Identifying variables associated with inaccurate self-monitoring of blood glucose: proposed guidelines to improve accuracy.

PURPOSE: This study was conducted to evaluate patients' proficiency in self-monitoring of blood glucose (SMBG). METHODS: Diabetes nurse educators in 4 suburban Minneapolis clinic sites surveyed the SMBG training/cure practices of 280 patients with type 1 and type 2 diabetes. Participant SMBG technique was measured by direct observation. Participants performed a finger puncture and used their own meters to measure the first blood sample. A second sample was measured on the HemoCue B Glucose analyzer, and a third sample was used to measure hemoglobin. The series of tests were then repeated. If either of the 2 glucose tests was more than 15% from the HemoCue value, participants were reeducated about the manufacturer's suggested procedure. RESULTS: Of the 280 participants, 19% had blood glucose test results greater than the 15% limit for meter accuracy. After reeducation, 69% of those who had initially failed achieved acceptable results. The most significant problems were lack of periodic meter technique evaluation, difficulty using wipe meters, incorrect use of control solutions, lack of hand washing even when observed, and unclean meters. CONCLUSIONS: As a result of the study, guidelines were subsequently developed to evaluate meter accuracy in an outpatient setting. Further effort is needed to establish standards for evaluating SMBG.

Algorithms↗

PubMedDate not supplied

Tissue donation.

Explore the source record for details and available documents.

Family↗