Study of receptor-mediated neurotoxins released by HIV-1-infected mononuclear phagocytes found in human brain

Although there is growing evidence that neurotoxic molecules produced by HIV-1-infected mononuclear phagocytes damage neurons, the precise mechanisms of neuronal attack remain uncertain. One class of cytotoxin involves neuronal injury mediated via the NMDA receptor. We examined blood monocytes and brain mononuclear cells isolated at autopsy from HIV-1-infected individuals for the ability to release NMDA-like neuron-killing factors. We found that a neurotoxic amine, NTox, was produced by blood monocytes and by brain mononuclear phagocytes infected with retrovirus. In vivo injections of minute quantities of NTox produced selective damage to hippocampal pyramidal neurons. NTox can be extracted directly from brain tissues infected with HIV-1 and showed structural features similar to wasp and spider venoms. In contrast to NTox, HIV-1 infection did not increase the release of the NMDA excitotoxin quinolinic acid (QUIN) from mononuclear cells. Although we found modest elevations of QUIN in the CSF of HIV-1-infected individuals, the increases were likely attributable to entry through damaged blood-brain barrier. Taken together, our data pinpoint NTox, rather than QUIN, as a major NMDA receptor-directed toxin associated with neuro-AIDS.     

Unilateral injury of posterior parietal cortex and spatial learning in hooded rats

The influences of bilateral or unilateral injuries within the posterior parietal cortex (PPC) upon spatial learning in a water maze were examined in three experiments. Place-learning and response-learning were investigated in a four-alley 'Greek-cross' shaped water maze with extra-maze visual cues available. No differences were detected on any of several measures sensitive to learning between the lesion groups on the place-learning task. Microanalysis of behavior within trials revealed that animals with either bilateral or right unilateral PPC injuries committed significantly more total errors, initial alley entrance ('reference memory') errors, and re-entry ('working memory') errors in the response-learning paradigm than did either the control or left PPC-injured rats. No differences were detected between the latter two groups on these measures. Unilateral lesions resulted in asymmetrical placing responses ipsilateral to the injury 10 days after surgery whereas bilateral injuries resulted in asymmetrical placing with mixed directionality. The acquisition of the response-learning problem in the absence of visual cues was studied on animals prepared with unilateral lesions and housed post-operatively either in isolation or in a 'complex environment.' In the absence of visual cues both right and left PPC-injured rats committed more errors than sham controls, and differential post-surgical housing did not attenuate these impairments. These same animals were trained on the landmark navigation task. Although no differences appeared between the lesion groups, a generalized but transient facilitation of learning was observed in animals housed in the 'complex' environment. Unilateral injuries placed in sham controls failed to disturb retention of the landmark navigation strategy. Because none of the PPC-injured animals were deficient in the landmark task, a result which is contrary to observations in other laboratories, the influence of post-surgical recovery interval upon acquisition of the landmark navigation strategy was explored. Animals were prepared with right PPC injuries and trained following either a 5 or 35 day recovery interval. Only those animals limited to the short recovery interval proved to have a spatial deficit in the landmark task. It is concluded that injuries in the PPC of either hemisphere disturb egocentric spatial functions. However, animals with left PPC injuries are able to compensate by using allocentric visual cues if they are available. It is due to the special role played by the right PPC in complex visuospatial functions that animals with this injury are unable to compensate.     

全球表面活性剂市场动态

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Pattern separation in digital learning nets

Pattern separation is a new technique in digital learning networks which can be used to detect state conflicts. This letter describes pattern separation in a simple single-layer network, and an application of the technique in networks with feedback.<>     

Non-disjunction in human sperm: results of fluorescence in situ hybridization studies using two and three probes

Fluorescence in situ hybridization using two or three probes was utilized to estimate the incidence of diploidy, the incidence of disomy for the sex chromosomes and chromosomes 16 and 18, and the proportion of Y- and X-chromosome bearing sperm, in a series of normal males. Our results demonstrate the importance of using an approach capable of distinguishing disomy from diploidy, as most donors had levels of diploidy higher than the disomy levels of individual chromosomes. Our analyses suggest the existence of chromosome-specific mechanisms of paternal non-disjunction, as sex chromosome disomy was approximately 1.5 times as common as disomy 16, and over two times as common as disomy 18. In studies of gametic sex ratio, we found little evidence for marked deviation from an expected 1:1 ratio.     

CD18-independent mechanism of neutrophil emigration in the rabbit lung after ischemia-reperfusion

BACKGROUND: Reperfusion of ischemic lung causes an inflammatory pulmonary vascular injury characterized by increased vascular permeability and migration of inflammatory cells into the alveoli. Migration of neutrophils into the alveolus during reperfusion after 24 hours of unilateral pulmonary artery occlusion has been shown to be in part dependent on the CD18 adhesion molecule on the cell surface. The current study investigated whether reperfusion lung injury after a 1-hour period of complete lung ischemia was CD18 dependent. METHODS: Eighteen rabbits were assigned to one of three groups. Groups 1 and 2 were subjected to one hour of in situ right hilar occlusion followed by 2 hours of reperfusion. Group 3 was subjected to identical surgical dissection but the right hilum was never occluded. Group 1 rabbits received saline solution (1 mL/kg) before hilar occlusion and group 2 rabbits, monoclonal antibody 60.3, a blocking antibody for the CD18 adhesion molecule on the neutrophil surface (2 mg/kg). In 3 of the antibody-treated rabbits, flow cytometry was performed on blood neutrophils before and after administration of the antibody and 120 minutes after reperfusion. RESULTS: The rabbits in groups 1 and 2 had significantly increased alveolar neutrophil infiltrate and increased pulmonary vascular resistance compared with the rabbits in group 3. However, there was no significant difference between group 1 (saline solution treated) and group 2 (antibody treated). Antibody treatment did not block migration of neutrophils into the alveoli. Flow cytometry of circulating neutrophils demonstrated that CD18 was upregulated after reperfusion and that CD18 was fully blocked after antibody treatment for the duration of the study. CONCLUSIONS: We conclude that a 1-hour period of warm ischemia followed by reperfusion results in upregulation of CD18 but that emigration of the neutrophils into the alveoli is not CD18 dependent in this injury.