Incidental brain lesions on magnetic resonance imaging and neurobehavioral functions in the apparently healthy elderly.

BACKGROUND AND PURPOSE: Controversies exist whether incidental neuroradiological brain lesions in the elderly are associated with depressed neuropsychological function. To address this important issue in a cross-sectional study, we related brain lesions on magnetic resonance imaging to a variety of cognitive and neurobehavioral function tests in an independent, normal elderly population. METHODS: We studied 73 independent asymptomatic elderly individuals (mean +/- SD age 70 +/- 6 years) to determine the relations between degree of brain atrophy, location and number of "lacunes," and grade of periventricular hyperintense lesions with a variety of cognitive and neurobehavioral function scores. RESULTS: We found that severity of neuroradiological changes increased while neuropsychological function scores declined with age. After adjustment for the effect of age, advanced periventricular hyperintensities, but not brain atrophy or patchy "lacunar" lesions, were associated with declines in all neuropsychological functions tested. CONCLUSION: We conclude that incidental advanced periventricular diffuse or patchy white matter changes may play a role in the development of cognitive and neurobehavioral impairments in apparently normal elderly persons.     

LMW heparin (anti-Xa) assays for clinical monitoring and pharmacokinetic studies on the automated coagulation laboratory (ACL).

Chromogenic anti-Xa activity procedures were developed for monitoring LMW heparins on the Automated Coagulation Laboratory 300 Plus (ACL, Instrumentation Laboratory) system. For daily monitoring, a "Routine" procedure was devised which allows accurate measurements between plasma levels of 0.1 and 1.0 u/ml LMW heparin. For lower levels a "Routine-Low" method was developed which assesses activities between 0.05 and 0.4 u/ml. Due to variabilities in dODs of individual baseline plasmas, levels below 0.05 u/ml might be inaccurate when pooled normal plasma is used to establish the reference curve. While levels less than 0.05 u/ml should rarely be encountered when monitoring LMW heparins for routine clinical use, pharmacokinetic studies require accurate measurements below that level. For this reason a "Research-High" and a "Research-Low" procedure was designed. For these procedures a study subject's own baseline plasma was used to establish the reference curve. The "Research-High" measures activities between 0.4 and 2.0 u/ml, the "Research-Low" between zero and 0.4 u/ml. The procedures have excellent within-run and inter-run coefficients of variation (less than 5%) and high levels of accuracies. Even inter-instrumental reproducibilities are less than 10%. Different manufacturers' LMW heparins can be analyzed by these assays. The procedures offer full automation, great cost-effectiveness due to lower reagent volumes, rapid turn-around time and great accuracy and reproducibility.     

ZZ domain is essentially required for the physiological binding of dystrophin and utrophin to beta-dystroglycan

An intracellular protein, dystrophin, plays an important role in keeping muscle fibers intact by binding at its N-terminal end to the subsarcolemmal cytoskeletal actin network and via its C-terminal end to the transmembraneous protein beta-dystroglycan. Duchenne muscular dystrophy is caused by the loss of dystrophin, which can result from the loss of this binding. The N-terminal part of the latter binding site of dystrophin has been well documented using overlay assay and X-ray diffraction assays. However, the binding site at the C-terminal region of dystrophin has not been examined in detail. In the present work, we report a detailed analysis of the C-terminal binding domain as follows. (1). The full binding activity corresponding to the effective binding in vivo is expressed by the dystrophin fragment spanning amino acids 3026-3345 containing the ZZ domain at the C-terminus. Determination of this binding range is important not only for understanding of the mechanism of dystrophy, but also useful for the design of truncated dystrophin constructs for gene therapy. (2). The ZZ domain binds to EF1 domain in the dystrophin fragment to reinforce the binding activity. (3). The cysteine 3340 in the ZZ domain is essential for the binding of dystrophin to beta-dystroglycan. A reported case of DMD due to missense mutation C3340Y may be caused by inability to fix dystrophin beneath the cell membrane. (4). The binding mode of utrophin is different from that of dystrophin. The difference is conspicuous concerning the cysteine residues present in the ZZ domain.     

Quantitative studies on the neutralization reaction between African horse-sickness virus and antiserum

Summary Kinetic neutralization curves formed with African horse-sickness virus were studied by the plaque reduction technique. There was no recovery phase in surviving virus titer during a 60-minute incubation period at 37°C when antiserum was diluted 1100 or more.Factors affecting the accuracy of the serum neutralization test in tube cultures of monkey kidney stable (MS) cells were studied to ascertain optimal conditions. Dose-response patterns, variations within and between tests, and the relationship between the amount of virus and serum titers were examined to develop a test procedure showing accuracy of less than a 3-fold dilution deviation under ordinary circumstances.With antisera against 8 different types of AHS virus, it was demonstrated that there is linear relationship between the amount of serum antibody and amount of virus neutralized. When tested in MS cell tube cultures, neutralization slopes of all AHS virus types ranged between 1.33 and 1.59. A decrease in the slope was noticed when tested in mice.This work was undertaken at the Near East Animal Health Institute, a project established by the United Nations Development Program Special Fund through the Food and Agriculture Organization in cooperation with the Ministry of Agriculture of Iran.     

Mechanisms of blood coagulation induced by latex particles and the roles of blood cells

Latex particles with highly negative or positive charges shortened the clotting time of whole blood and platelet-rich plasma and activated platelet factor 3. Platelet-poor plasma was clotted by the particles with a highly negative charge, but not by those with a positive charge, except hydrophobic particles. Blood coagulation by positively-charged particles was attributed to platelet activation. An enhancement of blood coagulation was also observed in the presence of erythrocytes, leucocytes, their cell membranes or negatively charged phospholipids, and phosphatidylserine instead of platelets. Hydrophilic and low-charged particles suppressed blood coagulation.     

Ultrastructural, cytochemical, and biophysical aspects of mechanisms of bone matrix calcification

Primary calcification in embryonic ossification occurs as follows: crystallization within matrix vesicles, formation of calcified nodules, and finally the establishment of expansive calcified matrix. However, the participation of the matrix vesicles in other types of bone calcification, such as bone formation during bone remodeling in adults has not been examined sufficiently. We introduce our recent observations on the presence of matrix vesicles in aged bones. In addition, although it is well known that the extracellular fluid supersaturates the calcification crystal, hydroxyapatite, the specific mechanisms by which bone matrix calcify remain unclear. In order to further approach the mechanisms of bone matrix calcification, we also review ultrastructural and localizational alterations of the matrix organics according to the progression of calcification, and an evaluation of mineral micro-environment in the calcifying sites by energy-filter transmission electron microscopy.     

α2-Adrenergic receptor subtype alterations in the brainstem in the sudden infant death syndrome

Background: The sudden infant death syndrome (SIDS) is still the main cause of postneonatal infant death. However, the causes and mechanisms of SIDS have never been completely elucidated. Catecholamines, via α2-adrenergic receptor (α2-AR) interactions, are known to influence brainstem autonomic and respiratory activity. Aims: To examine the catecholaminergic system abnormalities in SIDS victims, we investigated the alterations of α2-AR subtypes. Subjects and methods: We examined the developmental changes of α2-AR subtypes in the brainstem, especially in cardiorespiratory nuclei, in 21 SIDS victims and 17 age-matched controls by means of immunohistochemical methods. For statistical analysis, the χ²-test or Fisher’s exact probability test was performed. Results: There was a significant decrease in α2A-AR immunoreactivity in the solitary nucleus and ventrolateral medulla (VLM) in the medulla oblongata in SIDS victims compared with in control cases, but there were no significant differences of the α2B and α2C-AR immunoreactivity in the brainstem between SIDS victims and controls. Conclusion: α2A-AR immunoreactivity was selectively decreased in the solitary nucleus and VLM in the medulla oblongata in SIDS victims, so there was no possibility that it was secondary to chronic hypoxia or repeated ischemia. It may be related to some impairment of the cardiorespiratory neuronal system. Therefore, SIDS victims may be vulnerable to asphyxia, hypoxia, and/or hypercapnia, and fail to exhibit brainstem responses.