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Over the past decade, clinical Alzheimer's disease research has been challenged with an increased interest in noncognitive symptomatology, commonly referred to as behavioural and psychological signs and symptoms of dementia (BPSD). In accordance, major attention is being paid to behavioural alterations in the phenotyping of transgenic mouse models. Besides an age-dependent decline of cognitive functions, the APP23 model was previously shown to exhibit cage activity disturbances, reminiscent of diurnal rhythm disturbances in Alzheimer patients. To further scrutinize these observations, circadian patterns of horizontal locomotor activity were assessed in 3-, 6- and 12-month-old APP23 mice and wild-type littermates in a test paradigm continuously recording cage activity over a period ranging from 1 to 3 days. At the age of 3 months, APP23 profiles resembled the wild-type pattern to a large extent, although minor differences were already noticeable. Six-month-old APP23 mice displayed an altered activity profile with a first indication of increased activity during the second half of the active phase, reminiscent of sundowning behaviour in Alzheimer patients. This bimodal overnight activity pattern became even more evident at the age of 12 months. The APP23 model was therefore shown to display an age-dependent development of cage activity disturbances and sundowning-like behaviour. A comparison is made with actigraphic recordings of human Alzheimer patients exhibiting sundowning behaviour. This first report of diurnal rhythm disturbances and sundowning-like phenomena in a transgenic mouse model greatly adds to the validity of the APP23 model.

Heterozygous APP23 mice, expressing human amyloid-precursor protein with the Swedish double mutation and control littermates, were subjected to behavioral and neuromotor tasks at the age of 6-8 weeks, 3 and 6 months. A hidden-platform Morris-type water maze showed an age-dependent decline of spatial memory capacities in the APP23 model. From the age of 3 months onwards, the APP23 mice displayed major learning and memory deficits as demonstrated by severely impaired learning curves during acquisition and impaired probe trial performance. In addition to the cognitive deficit, APP23 mice displayed disturbed activity patterns. Overnight cage-activity recording showed hyperactivity in the transgenics for the three age groups tested. However, a short 2-h recording during dusk phase demonstrated lower activity levels in 6-month-old APP23 mice as compared to controls. Moreover, at this age, APP23 mice differed from control littermates in exploration and activity levels in the open-field paradigm. These findings are reminiscent of disturbances in circadian rhythms and activity observed in Alzheimer patients. Determination of plaque-associated human amyloid-beta 1-42 peptides in brain revealed a fivefold increase in heterozygous APP23 mice at 6 months as compared to younger transgenics. This increase coincided with the first appearance of plaques in hippocampus and neocortex. Spatial memory deficits preceded plaque formation and increase in plaque-associated amyloid-beta 1-42 peptides, but probe trial performance did correlate negatively with soluble amyloid-beta brain concentration in 3-month-old APP23 mutants. Detectable plaque formation is not the (only) causal factor contributing to memory defects in the APP23 model.

Deficiency of arylsulfatase A (ASA) causes the autosomal recessive lipidosis, metachromatic leukodystrophy (MLD). Performance on tests of activity, motor ability and learning/memory was assessed in ASA-deficient mice and normal controls at 3, 6 and 12 months-of-age. ASA-deficient mice showed consistently increased cage activity in all age groups, whereas open field activity was increased only in the 3-month-old group. Motor coordination and equilibrium, as tested in the rotarod test, was impaired in 12-month-old ASA-deficient mice. Passive avoidance learning was tested in the step-through box. Performance on this test was impaired in the 12-month-old group only. Spatial learning and memory abilities were tested in the Morris water maze. Six-month-old ASA-deficient mice displayed slightly impaired hidden-platform acquisition performance. Three-month-old animals, on the other hand, did not show any acquisition or retention defect on this task, notwithstanding significantly reduced swimming velocity. Acquisition training, both in the hidden- and visible-platform conditions of the Morris water maze, and retention performance during the probe trials were impaired in 12-month-old ASA-deficient mice. The hyperactivity, motor incoordination and slowing, and the age-related learning/memory defects, reported here in ASA-deficient mice, may relate to the decline of neuromotor and cognitive functions in MLD patients, and could be used as correlative or outcome measures in the study of MLD pathophysiology and treatment.

Fmr1 knockout mice are an animal model for fragile X syndrome, the most common form of heritable mental retardation in humans. Fmr1 knockout mice exhibit macro-orchidism and cognitive and behavioural deficits reminiscent of the human phenotype. In the present study additional behavioural and cognitive testing was performed. Knockouts and control littermates were subjected to a spatial learning test using a plus-shaped water maze. Animals had to learn the position of a hidden escape platform during training trials. The position of this platform was changed during subsequent reversal trials. Previously reported deficits in reversal learning were replicated, but we also observed significant differences during the acquisition trials. A plus-shaped water maze experiment with daily changing platform positions failed to provide clear evidence for a working memory impairment, putatively underlying the spatial learning deficits. Two different test settings were used to examine the reported deficit of Fmr1 knockout mice in fear conditioning. Conditioned fear responses were observed in a contextual fear test, and the ability to acquire an emotional response was tested by means of response suppression in a conditioned emotional response procedure. Neither protocol revealed significant differences between controls and knockouts.

An unusual case of a 62-year-old patient is presented with multiple coronary arteriovenous fistulas originating from both coronary arteries going into the pulmonary trunk.

In this study a model of acute respiratory failure due to viral pneumonia in rats, closely resembling ARDS, is presented. Severe respiratory failure with lethal outcome in four days was induced by infection concentrated Sendai virus aerosol. This model permits evaluation of different therapeutical approaches for improving gas exchange during ARDS. Furthermore, preliminary results of surfactant substitution therapy in this model are presented.

The effect of intratracheal surfactant administration was studied in rats with adult respiratory distress syndrome associated with infection with nebulized Sendai virus. Thirty-six hours after infection, animals (n = 7) showed severely impaired gas exchange and acidosis during artificial ventilation (PaO2 = 152.2 +/- 18.7, PaCO2 = 65.3 +/- 19.2, pH = 7.26 +/- 0.11) with a pressure-controlled mode, standard frequency of 35/min, peak airway pressure of 15 cm H2O (15/0), inspiratory/expiratory ratio of 1:2, and F1O2 = 1. Gas exchange improved (P = 0.02) with increased ventilator pressures with PEEP (25/4). Forty-eight hours after infection, blood gas tensions could no longer be significantly improved by these same ventilator settings (PaO2 = 123.8 +/- 31.0, PaCO2 = 95.1 +/- 43.6, pH = 7.12 +/- 0.16, n = 9). At this time, surfactant replacement dramatically increased arterial oxygenation within 5 min (PaO2 = 389.4 +/- 79.9) and resulted in a fourfold increase in PaO2 within 2 h. It is concluded that intratracheal surfactant administration is a promising approach in the treatment of respiratory failure during adult respiratory distress syndrome associated with viral pneumonia.

Sampling of canopy fluxes (throughfall and stemflow) below low structured vegetation with a small-scale, intricate canopy architecture is difficult, and representative sampling with most methods is questionable. In the present study, two sampling methods for canopy fluxes below grassland vegetation are compared. Method I sampled canopy fluxes of moisture inefficiently, because stemflow volumes were not quantitatively included. Canopy fluxes of ions calculated with method I necessitated assumptions on equal concentrations in actually sampled throughfall and non-sampled stemflow. Method II sampled canopy fluxes of ions quantitatively, because the total volume of throughfall and stemflow percolated through a mixed bed of ion exchange resins below the canopy. Ion-specific differences between the two methods were observed. For ions with foliar leaching, such as K+ and Ca2+, higher canopy fluxes were recorded with method II than with method I. In contrast, for ions with foliar uptake, such as NH4+ and NO3-, canopy fluxes were found to be less with method II than with method I. Canopy fluxes of inorganic nitrogen below Mesobrometum grassland were 2.35 and 1.52 kmol(c) ha(-1) year(-1) for methods I and II, respectively, and 2.85 and 7.90 kmol(c) ha(-1) year(-1) for K+. It is argued that these differences result from under-estimated (foliar leaching) or over-estimated (foliar uptake) concentrations in stemflow by the first method. Canopy fluxes for SO4(2-) were not statistically different, indicating that canopy exchange of SOx was quantitatively unimportant, and that both methods estimated atmospheric input equally well.

Air pollution can cause a decline in species through acidification of the habitat. New data suggest that the decline may be due to eutrophication rather than acidification. In Western Europe, eutrophication largely results from atmospheric ammonium deposition. The amount deposited on vegetation is a function of its canopy structure. Deposition on grasslands has been underestimated, and a significant amount of the deposited ammonium appears to be assimilated by the plant canopy. These quantities are sufficient to initiate changes in the competitive relations among the plant species.

Human peripheral blood (PB) mononuclear cells were depleted of T cells and subsequently of monocytes by counterflow centrifugation. The resulting B cell enriched fraction contained less than 3% T cells, 1 +/- 1% monocytes and 71 +/- 6% B cells. Approximately 56% of the B cells carried surface IgM (sIgM) and sIgD, the remaining 44% carried only one isotype (IgG, IgA, IgM or IgD). Using anti-delta or anti-mu-coated Ox red blood cells (OxRBC) the B cell enriched fraction was separated into a sIgD+ or sIgM+ and sIgD- or sIgM- fraction. The sIgD+ as well as the sIgM+ fraction responded (partially) to pokeweed mitogen (PWM) with plasma cell differentiation into cytoplasmic IgM (cIgM) containing cells. Cytoplasmic IgD+ cells were occasionally found in the sIgD+ or sIgM- fraction, but never in the sIgM+ fraction. Cells containing cIgG or cIgA were only found after stimulation of the sIgM- or sIgD- fraction, the latter also produced cIgM+ cells. In a second separation step of the sIgD- and sIgM- fraction with anti-alpha or anti-gamma-coated OxRBC it was shown that the cIgA+ and cIgG+ cells were derived from B cells expressing only sIgA or sIgG respectively. In conclusion, two major B cell subpopulations can be found in PB: a sIgM+D+ fraction, which gives rise to only cIgM+ plasma cells after PWM stimulation and a second population of B cells which express one heavy-chain isotype on their surface. These cells not only differentiate on PWM stimulation, but they also show a strong proliferative response.

Epithelioid sarcoma of the palm of 7 months' duration was observed in a 30-year-old man. Six months after wide surgical excision there was no evidence of recurrence or metastasis. By light microscopic examination the tumor showed typical nodular arrangement of malignant cells, with necrosis of these cells in the centers of the nodules. Patchy lymphocytic infiltrates were observed at the peripheries of the nodules and also extended in places between the tumor cells. Other types of inflammatory cells were practically absent. By electron microscopic examination it was noted that numerous neoplastic cells formed firm close contacts with lymphocytes. Considerable numbers of neoplastic ells so contacted were damaged or even disintegrated. The damaged tumor cells contained abundant lysosomes. The release of enzymes from these lysosomes in the disintegrating tumor cells might be an important factor underlying the extracellular tissue injury and necrosis so conspicuous in epithelioid sarcoma. The very slow growth of this neoplasm and its slow tendency to metastasize might be related to the high efficacy of lymphocyte-mediated defenses against this tumor.