Semantic (verbal) and figural memory impairment in alcoholics

In two separate studies, episodic semantic (verbal) and figural-memory abilities as measured by the Wechsler Memory Scale (Russell Method) are compared in middle-aged detoxified male alcoholics and controls. Both studies gave rise to similar findings. Alcoholics recalled significantly less verbal and figural material at both immediate recall and 30-min delayed recall than did the controls. Contrary to expectation, compared to controls, alcoholics did not have a greater differential deficit for the figural material as compared with the verbal or a greater differential deficit on delayed than on immediate memory. The percentage of material recalled at the delayed testing, when taken as a function of the amount of material recalled immediately, did not differ for the two groups on the semantic or figural tasks in either study. Thus, rates of forgetting were equivalent in alcoholics and controls suggesting that the alcoholics' deficit lies in the initial acquisition process. Whether that deficit is in encoding or initial retrieval processes remains to be investigated. Implications for future research are given.     

A procedure for purifying low-abundance protein components from the brain cytoskeleton-nuclear matrix fraction

We describe a preparative procedure for low-abundance proteins of the cytoskeleton-nuclear matrix fraction from frozen bovine brain. Strigent centrifugation and washing conditions in the preparation of the cytoskeleton-nuclear matrix fraction are avoided to minimize loss of nuclear material. A recently described horizontal isoelectric focusing column, which tolerates appreciable precipitation, is used. In concert with selection of urea concentration and temperature, this isoelectric focusing apparatus provides a new approach to the fractionation of this complex, relatively insoluble mixture of proteins and other components. In addition, a heated, sodium dodecyl sulfate-sizing column has been utilized in order to eliminate interactions between the desired low abundance proteins and more abundant contaminating proteins. Together these procedures purify a specific low-abundance protein sufficiently to be detected by Coomassie blue staining in two-dimensional gels. The methods are robust and can be applied to multiple, relatively large brain samples (150 g of crude grey matter per batch); thus they should facilitate partial peptide sequencing for brain proteins of this operational class.     

Maculopapular eruption with enlarged macrophages in eight patients receiving G-CSF or GM-CSF

In the last years, granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF) are being increasingly used and several cutaneous eruptions have been reported in relation to these treatments. In 1991 Horn et al. described three patients with maculopapular eruption that paralleled the time of infusion of GM-CSF. Two of the cases showed an increase in the number and size of macrophages in the biopsy specimen. Since then, several cases have been reported showing this histopathological alteration that has been considered characteristic of reaction to G-CSF or GM-CSF. Although maculopapular eruption with enlarged macrophages can appear after chemotherapy treatment, we have found that the presentation of this eruption after the beginning of cytokine treatment is suggestive of the involvement of G-CSF and GM-CSF in the eruption. We described eight cases of patients treated with G-CSF or GM-CSF that developed maculopapular eruptions with enlarged macrophages.     

The Role of Instructional Set on Alcoholic Performance

This study was conducted to determine whether alcoholic and control subjects respond differently to manipulations that either enhance personal involvement (PI) or reduce negative affect (R, relaxation) on tests of neuropsychological function. In Phase 1, 48 male alcoholics and 36 male control subjects completed neuropsychological tasks under standard instructional sets. In Phase 2, subjects completed equivalent forms of these tests under one of three randomly assigned conditions; the PI condition in which subjects were encouraged to identify specific ways of improving their performance, the R condition in which subjects participated in a short relaxation exercise designed to reduce anxiety, or a No Treatment (NT) condition in which no attempt to manipulate the subjects' involvement or affect was made. Alcoholics were inferior to controls in both Phase 1 and Phase 2 [Fs (1,82) > 5.03, ps < 0.03]. The experimental manipulation differentially affected measures of negative affect and effort in the predicted direction. There were no group x condition interactions. Alcoholic and control subjects responded comparably to the experimental manipulations. This investigation, in combination with others using related manipulations, reinforces the hypothesis that alcohol-related cognitives dysfunction reflects an underlying deficit in brain states.     

Lysosomal abnormalities in degenerating neurons link neuronal compromise to senile plaque development in Alzheimer disease

Antibodies to the lysosomal hydrolases, cathepsins B and D and β-hexosaminidase A, revealed alterations of the endosomal-lysosomal system in neurons of the Alzheimer disease brain, which preceded evident degenerative changes and became marked as atrophy, neurofibrillary pathology, or chromatolysis developed. At the earliest stages of cell atrophy, hydrolase-positive lysosomas accumulated at the basal pole and then massively throughout the perikarya and proximal dendrites of affected pyramidal neurons in Alzheimer prefrontal cortex and hippocampus, far exceeding the changes of normal aging. Secondary lysosomes as well as tertiary residual bodies (lysosomes/lipofuscin) increased implying stimulated, autophagocytosis and lysosomal system activation. Less affected brain regions, such as the thalamus, displayed similar though less extensive alterations. Certain thalamic neurons exhibited a distinctive lysosome-related abnormality characterized by the presence of cell surface blebs of varying size and number filled with intense hydrolase immunoreactivity. At more advanced stages of degeneration in still intact neurons, hydrolase-positive lipofuscin, particularly in the form of abnormal large aggregates, nearly filled the cytoplasm. Similar lipofuscin aggregates were oberved in abundance in the extracellular space following cell lysis and were usually associated with deposits of the β-amyloid protein. Degenerating neurons and their processes were the major source of these aggregates within senile plaques which contained high concentrations of acid hydrolases. We have shown in previous studies that these lysosomal hydrolases in plaques are enzymatically-active. The persistence of lysosomal structures in the brain parenchyma after neurons hyve degenerated is a striking and potentially diagnostic feature of Alzheimer disease which has not been observed, to our knowledge, in other degenerative diseases. The lysosomal response in degerating Alzheimer neurons represents a probable link between an early activation of the lysosomal system in at-risk, normal-appearing neurons and the end-stage contribution of lysosomes to senile plaque formation of emphasizes a slowly progressive disturbance of the lysosomal system throughout the development of Alzheimer disease.     

Using 16O35Cl to correct for chloride interference improves accuracy of urine arsenic determinations by inductively coupled plasma mass spectrometry.

We have observed inaccurate urine arsenic values with the method of isobaric fractionation, which was designed to correct for the 40Ar35Cl interference with 75As quantitation by inductively coupled plasma mass spectrometry. Isobaric fractionation, which is based on ion intensities at m/z 77 and 82, consistently underestimates the 40Ar35Cl interference and overestimates urine arsenic. We present an improved method for identifying the argon-chloride interference. We observed that signal intensities for the species 16O35Cl and 40Ar35Cl are proportional (I75 = 0.0295 x I51 - 14.7, r2 = 0.998; where Ix is the normalized ion intensity at m/z X) in water and urine, over a broad range of chloride concentrations (0-800 mmol/L). The proportionality constant is remarkably stable within a run (mean and SD, 0.0295 +/- 0.0023, based on 10 replicates of five chloride calibrators, 0, 100, 200, 400, and 800 mmol/L). Increased sensitivity (50-fold) for detecting the 40Ar35Cl interference provides improved accuracy for urine arsenic quantitation as demonstrated by a split-sample comparison with graphite-furnace atomic absorption spectrophotometry.     

The ''think test'': a further technique to elicit hyperventilation.

Hyperventilation can undermine cardiovascular homeostasis by generating autonomic imbalance, sympathetic dominance, hypokalaemia, and intracellular alkalosis with calcium ion shifts. The role of hyperventilation in episodic disorders such as arrhythmia and coronary vasospasm can be difficult to identify if the patient does not present in an attack and so a provocation challenge is required. Today, the standard challenge is the forced hyperventilation provocation test (FHPT). A capnograph enables the resting end-tidal PCO2 to be compared with the level 3 min after the period of overbreathing. We report the use of a patient-specific challenge. After the FHPT, the subject is invited to close his eyes and think about the circumstances of an attack, feelings and sensations experienced (breathing is not mentioned) or topics that were seen to disturb the rhythm of breathing when the medical history was taken. A fall of end-tidal PCO2 of 10 mmHg or more lasting at least one minute was taken as a positive response. Out of 57 patients with cardiovascular symptoms suggesting a hypocapnic influence, resting hypocapnia (end-tidal PCO2 = 30 mmHg) was present in 3 (5%). Of the remaining 54, the FHPT was positive in 16 (30%) and the 'think test' in 33 (61%). This suggests that patient-specific stimulation has advantages over an unspecific challenge in testing for episodic hypocapnia.