An infant formula toxicity and toxicokinetic feeding study on carrageenan in preweaning piglets with special attention to the immune system and gastrointestinal tract.

A toxicity/toxicokinetic swine-adapted infant formula feeding study was conducted in Domestic Yorkshire Crossbred Swine from lactation day 3 for 28 consecutive days during the preweaning period at carrageenan concentrations of 0, 300, 1000 and 2250 ppm under GLP guidelines. This study extends the observations in newborn baboons (McGill et al., 1977) to piglets and evaluates additional parameters: organ weights, clinical chemistry, special gastrointestinal tract stains (toluidine blue, Periodic Acid-Schiff), plasma levels of carrageenan; and evaluation of potential immune system effects. Using validated methods, immunophenotyping of blood cell types (lymphocytes, monocytes, B cells, helper T cells, cytotoxic T cells, mature T cells), sandwich immunoassays for blood cytokine evaluations (IL-6, IL-8, IL1ß, TNF-α), and immunohistochemical staining of the gut for IL-8 and TNF-α were conducted. No treatment-related adverse effects at any carrageenan concentration were found on any parameter. Glucosuria in a few animals was not considered treatment-related. The high dose in this study, equivalent to ~430 mg/kg/day, provides an adequate margin of exposure for human infants, as affirmed by JECFA and supports the safe use of carrageenan for infants ages 0-12 weeks and older and infants with special medical needs.

Cross-modal warning effects on reflexive and voluntary reactions.

Previous research has shown that warning signals can speed the onset of the startle-blink reflex. To relate this phenomenon to warning effects on voluntary reaction time (RT), the latencies of both reflexive and voluntary responses were measured for nine factorial combinations of warning and reflexogenic stimulus modalities. Previous failures to use factorial manipulations of warning (S1) and reaction (S2) stimulus modalities have led to conflicting results in both the reflex and RT literatures. Using psychophysically matched warning signals, we found a facilitation of reflex latency that was nonspecific with regard to S1 and S2 modality. Furthermore, there was no support for the widely held assumption that visual stimuli are inherently less alerting than auditory and cutaneous stimuli. A between-group comparison showed that simultaneous voluntary reactions do not distort the reflex facilitation effect. These results support the validity of reflex facilitation as a simple model system for studying warning effects on sensorimotor reactions.

Design, analysis, and implementation of a telemedicine remote consultation and diagnosis session playback using discrete event system specification.

Telemedicine remote consultation and diagnosis (RCD) software is a complex and distributed system. RCD allows physicians to collaborate on radiology or pathology cases from distributed geographic locations. It is very important to simplify design, construction, and maintenance of such a system. Currently, object-oriented design methodology is used to design and develop a software system in a modular fashion. Object-oriented software is made of various objects that work together. From the design of the software system, we get information about object methods and inheritance. We also get information about which objects are contained in a particular object and which objects are used by another object. One important element that the traditional object-oriented design misses is time. We propose the use of discrete event system specification (DEVS) in the design and analysis of a software system, such as RCD. With DEVS, coupling between objects can be specified explicitly and an object behavior can be shown in time. We introduce DEVS, show the time-line analysis of Remote Consultation and Diagnosis session playback using DEVS, and then describe its implementation.

The TAP complex influences allorecognition of class II MHC molecules.

The influence of the TAP complex on T-cell allorecognition of MHC class II molecules was examined using human B-cell lines that have mutations in the TAP 1 or 2 genes. The TAP mutations led to the loss of allorecognition for two of 28 anti- HLA-DR T-cell clones. Restoration of TAP expression by transfection of a TAP 2 cDNA clone led to recovery of the alloresponse for both clones. These results could be explained in two ways. First, TAP dependence could reflect specificity for a peptide derived from an MHC class I molecule that is less efficiently generated by the endocytic pathway in the TAP-deficient stimulator cells owing to reduction in surface class I expression. The proliferative responses of these clones to the TAP-deficient stimulator cells was not restored by rescue of cell-surface expression of class I molecules by low temperature culture or by the addition of class I-binding peptides. These data therefore favor the alternative explanation that class II loading by some peptides is TAP dependent. Circumstances that lead to the amplification of this minority pathway of endogenous presentation by class II MHC molecules may have the potential to interrupt self-tolerance.

Knowledge-based design of artificial worlds.

We review the concepts of knowledge representation and modelling and simulation methodology which facilitate computer exploration of alternative artificial worlds, such as self-sufficient human habitats. An object-oriented computer environment which supports such simulation studies is briefly described. A simplified example of an artificial world model is given to demonstrate the power of the approach.

Stimulus duration as an age-dependent factor in reflex blinking.

Alternative hypotheses of differential development of auditory and visual systems versus temporal-processing systems were tested to explain prior adult-infant differences in reflex blink latency. The present study removed a confound between stimulus modality and duration, present in prior work, and determined whether age interacted with modality or with duration when they were varied orthogonally. Reflexes were elicited from human adults and infants under 4 stimulus conditions: flash and click, delivered singly and in trains. Age interacted only with duration to affect latency and elicitation probability, reflex characteristics which depend on adequate triggering by a transient change at onset. In contrast, age did not interact with duration to affect peak amplitude which presumably depends on temporal integration. Findings are compatible with the hypothesis that processes or structures, specialized for differentiation of transient stimulus change, mature at a different rate than those specialized for integration of stimulus energy over time.

Bacterial predator-prey interaction at low prey density.

A bacterial predator-prey interaction was studied using Bdellovibrio and bioluminescent prey bacteria. The attacking bdellovibrio causes decay of bioluminescence, which is correlated with bdellovibrio penetration into the prey. The behavior of the prey and predator populations over time was found to be well described by a Lotka-Volterra model. By using this model, the probability of bdellovibrio penetration after encountering a prey cell was found to be approximately 3.0%. The prey density required to give the bdellovibrios a 50% chance of survival was calculated to be at least 3.0 x 10 cells per ml, and the density required for population equilibria was calculated to be about 7 x 10 prey bacteria per ml. These values, not generally characteristic of natural habitats, suggest that the existence of Bdellovibrio in nature is limited to special ecological niches.

Regulation of phospholipid metabolism in differentiating cells from rat brain cerebral hemispheres in culture. Serine incorporation into serine phosphoglycerides: base exchange and decarboxylation patterns.

The patterns of serine metabolism into phospholipids of cultured brain cells was examined. Labeled serine was incorporated predominantly into serine- ad ethanolamine-containing phospholipids and sphingolipids. The highest rates of labeling were observed in the (1)acyl-(2)acyl- and (1)alkyl-(2)acyl-serine phosphoglyceride fractions. Serine incorporation into both compounds appears to proceed via a base exchange mechanism. A decrease in the rate of serine phosphoglycerides labeling and a depletion of the ATP levels were observed when oligomycin or the calcium ionophore A23187 was added to the incubation medium. The inhibition of serine incorporation by A23187 could be partially reversed following addition of 10 mM CaCl2. Based on these findings it is suggested that in addition to demonstrating the energy-independent calcium-stimulated pathway, there may also be an energy related pathway. Formation of ethanolamine phosphoglycerides, as a result of serine phosphoglycerides decarboxylation, has been analyzed by using a simplified compartmental model. Of the 0.67 nmol/mg of protein turned over per h in the diacylserine phosphoglyceride compartment, 0.14 nmol/mg of protein are converted into the ethanolamine phosphoglycerides. In a similar manner, of the 0.09 nmol/mg of protein turned over per h in the (1)alkyl-(2)acyl-serine phosphoglyceride compartment, 0.014 nmol/mg of protein is converted into the (1)alkyl-(2)acyl-ethanolamine phosphoglyceride. These figures provide a first indication that a considerable portion of the ethanolamine phosphoglycerides in cultured brain cells is formed via a direct decarboxylation of the serine phosphoglycerides. In estimating the rates of (1)alkenyl-(2)acyl-ethanolamine phosphoglyceride formation from (1)alkyl-(2)acyl-ethanolamine phosphoglyceride the precursor-product specific activity crossover point could not be established. Mathematical analysis, however, enabled us to estimate the flux from the former into the latter as 0.04 nmol/mg of protein per h. A scheme for the possible metabolic interconversions of the ether bond containing serine and ethanolamine phosphoglycerides is proposed.