Mucosal epithelial cells and Langerhans cells are targets for infection by the immunosuppressive type D retrovirus simian AIDS retrovirus serotype 1

Simian acquired immune deficiency syndrome (SAIDS) caused by the type D retrovirus SRV-1 results in opportunistic infections and a spectrum of oral lesions similar to those seen in humans with AIDS. To better understand the pathogenesis of these oral lesions we have retrospectively examined the oral mucosa from ten rhesus monkeys that died with SAIDS and prospectively examined the oral mucosa of ten additional animals inoculated with SRV-1 to determine at what time, and in what cells SRV-1 infection of the oral mucosa occurs. Using single and double label immunohistologic techniques, and electron microscopy we detected SRV-1 in clusters of oral epithelial cells and rare Langerhans cells as early as 1 month postinoculation.     

Neuropeptide gene expression and neural activity: Assessing a working hypothesis in nucleus caudalis and dorsal horn neurons expressing preproenkephalin and preprodynorphin

1. The working hypothesis that neuropeptide gene expression in a neuron is an indicator of that neuron's physiological activity is discussed. 2. Representative examples from the literature are presented to support the hypothesis. 3. Further, we discuss the regulation of expression of two opioid peptides, preproenkephalin and preprodynorphin, in laminae I and II of the spinal cord and in nucleus caudalis of the trigeminal nuclear complex, where they may play a role in pain modulation. 4. The expression of the opioid peptide genes can be induced by both painful and nonnoxious stimuli in neurons in time-dependent and sensory-specific fashions.     

A distributed knowledge-based approach to flexible automation: The contract net framework

This article applied distributed artificial intelligence to the real-time planning and control of flexible manufacturing systems (FMS) consisting of asynchronous manufacturing cells. A knowledge-based approach is used to determine the course of action, resource sharing, and processor assignments. Within each cell there is an embedded automatic planning system that executes dynamic scheduling and supervises manufacturing operations. Because of the decentralized control, real-time task assignments are carried out by a negotiation process among cell hosts. The negotiation process is modeled by augmented Petri nets —the combination of production rules and Petri nets—and is excuted by a distributed, rule-based algorithm.     

Characterization of the calcium sensitivity of differentiation in SCC-13 human squamous carcinoma cells

Summary The sensitivity to calcium of the human squamous carcinoma cell line, SCC-13, was demonstrated and characterized. Cultures grown to confluence in the presence of 0.2 to 2 mM calcium had approximately 10-fold higher levels of particulate transglutaminase activity and envelope competence than those grown in low calcium (0.025 to 0.05 mM) medium. Raising the calcium from 0.025 to 1.8 mM induced expression of this enzyme and of competence over the course of a week. Conversely, for cultures grown to confluence in 1.8 mM calcium, subsequent reduction of calcium to 0.025 mM resulted in a substantial decline in transglutaminase over a similar time period. Immunoprecipitable transglutaminase was clearly identifiable in cultures grown in 1.8 mM calcium-containing medium but not in those grown in low calcium medium or in the presence of retinoic acid, suggestive of regulation at the level of mRNA accumulation or translation rather than posttranslational modification. This research was supported by Public Health Service grant AR 27130 from the National Institute of Arthritis, Musculoskeletal and Skin Diseases, Bethesda, MD, and National Research Service postdoctoral fellowship ES 05336 from the National Institute of Environmental Health Sciences, Research Triangle Park, NC.     

Comparative efficiencies of bispecific F(ab′γ)2 and chimeric mouse/human IgG antibodies in recruiting cellular effectors for cytotoxicity via Fcγ receptors

Summary The three forms of Fc receptor carried by monocytes (FcRI, II) and natural killer (NK) cells (FcRIII) are all capable of mediating cell lysis. Here we compare the use of F(ab)₂ bispecific antibodies, specifically targetting individual FcR, and chimeric IgG mouse/human antibodies which are capable of targetting all FcR, for their ability to mediate target cell destruction. The derivatives are prepared by linking hinge sulphydryl residues via tandem thioether bonds, using a bismaleimide crosslinker: Fab from an anti-FcR mAb linked to Fab from a common anti-target mAb (BsAb), or Fab from the common anti-target mouse antibody linked to human Fc (FabFc or bisFabFc). All the derivatives targetting chick red blood cells gave efficient lysis, although different effector cell donors yielded differences in both the lytic levels achieved and the comparative efficiencies of derivatives. In contrast, significant lysis of the guinea pig lymphoblastic leukaemia, L₂C, regularly resulted only via the anti-FcRIII BsAb and the chimeric derivatives. These results suggest that the chimeric, Fc-containing derivatives mediate tumour cell lysis principally through FcRIII on NK cells. This is in contrast to the situation with the chick red blood cells where the chimeric derivatives appear capable of lysing erythrocytes by utilizing either monocytes or NK cells, because significant (50%) lysis occurred with effector cell populations magnetically depleted through either FcRII or FcRIII. A major difference between these two types of antibody derivative was their ability to function in the presence of high concentrations of normal human Fc. The lysis mediated by BsAb reactive with FcRI or II was unaffected by the presence of human Fc at 2.5 mg/ml (a concentration comparable with that yielded by IgG in plasma) whereas the BsAb recognizing FcRIII and all the Fc-containing derivatives were completely inhibited.This work has been supported by Tenovus, the Cancer Research Campaign, the Leukaemia Research Fund, Italfarmaco, Milano, Italy and the Imperial Cancer Research Fund     

The thalamocortical contribution to epilepsy

The experimental literature has dealt intensively with the cortical contribution to epilepsy. Possibly because of the direction of technological advance, much less attention has been paid to the role of other structures. A model which emphasizes the role of some of those non-cortical structures, specifically that of thalamocortical modulation of cortical excitability, is developed. Some aspects of the petit mal seizure, a seizure type considered by some investigators to involve thalamocortical mechanisms, are predicted by the model. Although the thalamocortical mechanisms under study are not the only mechanism underlying seizures, a full understanding of the phenomenology of epilepsy needs to take into account the role of subcortical modification of cortical activities in addition to other mechanisms. Gloor has described two types of epileptogenesis: type I characteristic of non-convulsive seizure and type II characteristic of convulsions. There is disagreement as to whether or not the two mechanisms represent qualitatively different phenomena. Utilizing the thalamocortical model, it can be shown that the two types of epileptogenesis are qualitatively different. Furthermore, the thalamocortical model leads to a possible explanation of clinically different profiles of antipileptic efficacy of medications.