The effects of endogenous interleukin-10 on gray matter damage and the development of pain behaviors following excitotoxic spinal cord injury in the mouse.

Interleukin-10 (IL-10) has been utilized as a neuroprotective agent in experimental models of spinal cord injury because of its potent anti-inflammatory properties. Previous studies have delivered a single dose (5 microg) of IL-10 following experimental spinal cord injury in the rat, and demonstrated various degrees of neuroprotection. However, the role of endogenous production of IL-10 has not been considered. Therefore, the purpose of the current study was to establish the role of endogenous IL-10 and demonstrate the true potential of exogenous IL-10 administration through the use of IL-10((-/-)) mice. Using the quisqualic acid model of spinal cord injury, we examined the extent of gray matter damage and onset of injury-induced pain behaviors at various time points following injury in wild-type vs. IL-10((-/-)) mice. Additionally, IL-10 was reconstituted in IL-10 deficient mice by the intraperitoneal administration of 50 ng recombinant murine (rm) IL-10 30 min following quisqualic acid injection. Animals were observed daily following injury for the onset of pain-behaviors. At days 1, 7, and 14 following injection, lesion analysis revealed a greater extent of damage at early time points (1 day, 7 days) following injury in the IL-10((-/-)) animals as compared with wild-type animals. However, by 14 days post-experimental spinal cord injury, the extent of damage between the two groups was not significant. IL-10((-/-)) animals that received the single (50 ng) rmIL-10 injection following injury displayed gray matter damage patterns similar to wild-type animals. The pronounced early damage noted in the IL-10((-/-)) animals was associated with an approximately two-fold increase in peripheral neutrophils, an index of an innate immune response to injury, compared with wild-type mice. In addition, wild type and IL-10((-/-)) animals receiving rmIL-10 demonstrated a delay in the onset of injury-induced pain behaviors. However, by 14 days post-experimental spinal cord injury the overall incidence of pain behaviors was similar between all treatment groups. Therefore, the absence of IL-10 expression accelerates the kinetics of lesion expansion, the onset of pain behaviors, and the peripheral immune response to spinal cord injury. Endogenous IL-10 and low doses of exogenous IL-10 are neuroprotective at 1 and 7 days following injury. Therefore, the results of the current study suggest that low dose IL-10 administration acutely following spinal cord injury has potential as a therapeutic agent for limiting tissue loss following injury.

Computational studies of gene regulatory networks: in numero molecular biology.

Remarkable progress in genomic research is leading to a complete map of the building blocks of biology. Knowledge of this map is, in turn, setting the stage for a fundamental description of cellular function at the DNA level. Such a description will entail an understanding of gene regulation, in which proteins often regulate their own production or that of other proteins in a complex web of interactions. The implications of the underlying logic of genetic networks are difficult to deduce through experimental techniques alone, and successful approaches will probably involve the union of new experiments and computational modelling techniques.

Edge enhancement and edge-enhanced correlation with photorefractive polymers.

We demonstrate a simple all-optical realization of programmable edge enhancement and edge-enhanced correlation using novel photorefractive polymers. We show that the higher non-Bragg order in a two-beam coupling scheme contains the edge enhancement of the object when placed in the path of one of the incident beams. Also, this arrangement provides a scheme for writing joint transform correlation dynamic holograms, which can be read by a third beam. The correlation is edge enhanced, and the correlation peak increases with the applied bias voltage. Numerical results without and with beam fanning are presented. Theoretical predictions are reconciled with experimental results.

Biotechnology core laboratories: An overview.

An assessment of the capabilities of biotechnology core facilities requires access to current data on state-of-the-art technologies, personnel, space, services, financial issues, and the demand for such facilities. Data on these topics should be useful to researchers, facility personnel, administrators, and granting agencies.To obtain such data, the Association of Biomolecular Resource Facilities (ABRF) conducted a general survey on the operation and technical capabilities of core facilities. A total of 81 ABRF core laboratories voluntarily responded to the survey. Just over 60% of the respondents were from academic institutions, with the remaining located in research institutes, industry, and one U.S. government laboratory. Fifty laboratories provided financial data, with 47 of these operating on a nonprofit basis. Four laboratories were fully self-supporting from user fees.A typical facility had three full-time staff members and occupied approximately 1100 square feet (ft(2)). The most frequently offered services were N-terminal protein sequencing, protein fragmentation, peptide synthesis and purification, amino acid analysis, DNA synthesis, and DNA sequencing. One third of the facilities provided mass analysis by matrix-assisted laser desorption and ionization (MALDI) mass spectrometry, a recently introduced service that has been offered on an average for 3 years. Another relatively new service, bioinformatics support, is offered by about one third of the responding laboratories.

Simple central pattern generator model using phasic analog neurons.

Many biological neurons (called phasic or adapting neurons) display neural adaptation: their response to a constant input diminishes with time. A simple method of adding adaptive firing thresholds to existing analog (or graded-response) neural models is described. A half-center central pattern generator is modeled using two mutually inhibitory phasic analog neurons. Hopf bifurcation analysis shows that oscillatory solutions will arise if the mutual inhibition is sufficiently strong, and allows us to characterize the stability of the cycles which arise.

The anti-angiogenic agent fumagillin covalently modifies a conserved active-site histidine in the Escherichia coli methionine aminopeptidase.

Methionine aminopeptidase (MetAP) exists in two forms (type I and type II), both of which remove the N-terminal methionine from proteins. It previously has been shown that the type II enzyme is the molecular target of fumagillin and ovalicin, two epoxide-containing natural products that inhibit angiogenesis and suppress tumor growth. By using mass spectrometry, N-terminal sequence analysis, and electronic absorption spectroscopy we show that fumagillin and ovalicin covalently modify a conserved histidine residue in the active site of the MetAP from Escherichia coli, a type I enzyme. Because all of the key active site residues are conserved, it is likely that a similar modification occurs in the type II enzymes. This modification, by occluding the active site, may prevent the action of MetAP on proteins or peptides involved in angiogenesis. In addition, the results suggest that these compounds may be effective pharmacological agents against pathogenic and resistant forms of E. coli and other microorganisms.

Holographic recording in specially doped lithium niobate crystals.

A set of twelve specially doped lithium niobate crystals were grown to test the effect of the dopant on holographic recording in the crystals via the photorefractive effect. The crystals were doped with Ce, Co, Cr, Cu, Fe, Mn, Ni, Rh, Tb, Fe:Ce, Fe:Cr, and Fe:Mn. The transmission spectra was measured for each crystal and holograms have been written in each of the crystals with wavelengths from 457 nm to 671 nm. The wavelength sensitivity, scattering, and stability of the holograms varied substantially among the crystals. A qualitative description of the hologram's properties and a comparison of sensitivities between the crystals will be presented.

Explosives detection with a frequency modulation spectrometer.

An explosives detection instrument was designed and tested at SRI International. The instrument uses frequency modulation spectroscopy with midinfrared lead-salt diode lasers to perform high-sensitivity detection of characteristic nitrogen-containing decomposition products of explosives. Ultimately, the instrument should be capable of detecting and identifying subpicogram levels of plastic explosives, which would be suitable for screening passengers at airports. Using the laboratory breadboard instrument and two different explosive vapor generators, we demonstrated a lower limit of detection of 5-10 pg for cyclotrimethylene trinitramine and linearity of the signal over an order of magnitude.

Design of a bipolar composite filter by a simulated annealing algorithm.

We present the design of a bipolar composite filter (BCF) by a simulated annealing algorithm. By minimizing the energy function of the system, we construct an out-of-plane rotation-invariant bipolar filter. We show that the BCF offers high pattern discrimination capability and can easily be implemented with an electronically addressed spatial light modulator.

Differential effects of prolonged restraint stress on proenkephalin gene expression in the brainstem.

Enkephalins have been discovered in various regions of the brain involved in cardiovascular regulation. The primary source of plasma Met-enkephalin released in response to stress, appears to be from sympathetic nerves. However, levels of Met-enkephalin are 2-3-fold higher at 2 min versus 30 min of restraint stress. Therefore, the purpose of this investigation was 2-fold; to determine whether proenkephalin gene expression is altered in the brainstem during restraint stress, and whether the magnitude of the change is attenuated with prolonged stress. Proenkephalin mRNA levels were compared in the area postrema (AP), nucleus tractus solitarius (NTS), rostral (RVLM) and caudal ventrolateral medulla (CVLM) following 2 and 30 min of restraint stress. During 2 min restraint stress, there was an approximately 1 fold increase in proenkephalin gene expression in the NTS, CVLM and RVLM with a approximately 50% decrease in the AP. With 30 min restraint stress, the increase in proenkephalin gene expression was maintained in the CVLM and RVLM, however mRNA levels had returned to control levels in the NTS and were approximately 1-fold higher than control in the AP. If the increases of proenkephalin gene expression in the NTS, CVLM and RVLM reflect changes in enkephalinergic neuronal activity in those regions, the alterations in enkephalinergic neuronal activity may be an important regulator of blood pressure homeostasis.

Vintage growth and population density: an empirical investigation.

"This paper tests a central prediction of vintage growth models of urban structure: that there are discontinuities in the population density function. The data set covers quarter sections in Chicago in 1980. Using such highly disaggregated data is critical because discontinuities are less likely to be found the larger is the unit of observation. Both a switching regression model and a nonparametric estimator reveal discontinuities and upward-sloping segments in the function, which supports the vintage growth model."

Proenkephalin gene expression is altered in the brain of spontaneously hypertensive rats during the development of hypertension.

Enkephalins have been discovered in various regions of the brain involved in cardiovascular regulation. Sympathoadrenal hyperactivity and altered baroreflex activity have been implicated in the development of hypertension. The purpose of this investigation was to determine whether proenkephalin gene expression is altered in the arterial baroreceptor reflex region of the brain and in neurons involved in regulating sympathetic outflow, during the development of hypertension. Proenkephalin mRNA levels were compared, using in situ hybridization, in 4- and 14 week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Systolic blood pressure was measured by tail-cuff impedance plethysmography. There were no differences in blood pressure at 4 weeks, however by 14 weeks resting systolic blood pressure was approximately 40% higher in SHR (162.5 +/- 1.6 vs. 117.3 +/- 1.5 mmHg). Proenkephalin gene expression in the nucleus tractus solitarius (NTS), caudal (CVLM) and rostral ventrolateral medulla (RVLM) was lower (approximately 67, 50, and 55%, respectively) in the SHR at 14 weeks. However, in the locus coeruleus (LC), anterior (AH) and lateral hypothalamus (LH), proenkephalin mRNA was significantly increased (approximately 50, 100 and 100%, respectively) in the SHR. The decrease in proenkephalin mRNA in the NTS, CVLM, and RVLM may attenuate arterial baroreceptor reflex activity, while the increase in proenkephalin mRNA in the LC, AH and LH may increase sympathetic tone by inhibiting the activity of sympathodepressor preganglionic neurons in the intermediolateral cell column of the spinal cord.

Alcohol, personality traits, and high risk driving: a comparison of young, drinking driver groups.

Four types of drinking driver groups were compared with each other and also with two nondrinking driver groups on sensation seeking, social responsibility, and hostility. Groups were also compared on traffic violations, accidents, alcohol consumption, frequency of driving after drinking, frequency of driving impaired, and perception of driving risk taking after drinking. Drivers under the influence apprehended in conjunction with an accident or moving violation had significantly greater alcohol consumption, frequency of driving after drinking, frequency of driving impaired, traffic violations, accidents, and self rating of risk taking after drinking in comparison with other groups.

Personality traits and behaviors of alcohol-impaired drivers: a comparison of first and multiple offenders.

Using an interview and questionnaire format, 358 driving under the influence of alcohol (DUI) first offenders and 141 DUI multiple offenders were compared on measures of personality traits, drinking behavior and problems, and driving behavior and history. In addition, official driving records for the two groups were compared. Results indicated that multiple offenders were significantly higher in hostility, sensation seeking, psychopathic deviance, mania, and depression than first offenders. Multiple offenders were significantly lower in emotional adjustment and assertiveness. Multiple offenders had significantly more nontraffic arrests, accidents, and traffic tickets than first offenders. They also consumed significantly more alcohol, evidenced more alcohol problems, and had higher BACs at the time of arrest than first offenders. Results are discussed in terms of general problem behavior and implications for intervention and treatment.

Female DUI offenders: a comparison to male counterparts and an examination of the effects of intervention on women's recidivism rates.

Female DUI offenders who participated in a controlled, random assignment DUI intervention study, the Mississippi DUI Probation Follow-Up Project, were compared to their male counterparts on demographic, drinker status and recidivism variables. In comparison to men, women in the project were less likely to be married, more likely to be between 30 and 50 years of age, less likely to have less than a 9th grade education, less likely to be screened as a high-problem-risk drinker, less likely to have prior DUI and public drunkenness arrests and less likely to recidivate. The effects of short-term rehabilitation, 1 year's probation and administration of the Life Activities Inventory-Current Status Questionnaire (LAI-CSQ) on the long-term recidivism rates of women were examined. The analysis for screened low-problem-risk women was inconclusive due to lack of statistical power. However, the repeated administration of the LAI-CSQ was detrimental for screened high-problem-risk women and tended to be detrimental for women with fewer than 12 years of education. Implications for intervening with female DUIs are discussed.

Behavior and personality traits among DUI arrestees, nonarrested impaired drivers, and nonimpaired drivers.

Eight types of drinking driver groups were compared on several personality and behavior traits. It was found that impaired drivers arrested after an accident or moving violation were significantly higher in hostility, psychopathic deviance, nontraffic arrests, frequency of impaired driving, accidents after drinking, and drinks consumed per week than impaired drivers caught in roadblocks. Neither impaired drivers stopped in roadblocks nor impaired drivers never arrested differed from nonimpaired drinking drivers or nondrinking drivers on most measures examined.

Phosphatidylinositol-specific phospholipase C of Bacillus cereus: cloning, sequencing, and relationship to other phospholipases.

The phosphatidylinositol (PI)-specific phospholipase C (PLC) of Bacillus cereus was cloned into Escherichia coli by using monoclonal antibody probes raised against the purified protein. The enzyme is specific for hydrolysis of the membrane lipid PI and PI-glycan-containing membrane anchors, which are important structural components of one class of membrane proteins. The protein expressed in E. coli comigrated with B. cereus PI-PLC in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, as detected by immunoblotting, and conferred PI-PLC activity on the host. This enzyme activity was inhibited by PI-PLC-specific monoclonal antibodies. The nucleotide sequence of the PI-PLC gene suggests that this secreted bacterial protein is synthesized as a larger precursor with a 31-amino-acid N-terminal extension to the mature enzyme of 298 amino acids. From analysis of coding and flanking sequences of the gene, we conclude that the PI-PLC gene does not reside next to the gene cluster of the other two secreted phospholipases C on the bacterial chromosome. The deduced amino acid sequence of the B. cereus PI-PLC contains a stretch of significant similarity to the glycosylphosphatidylinositol-specific PLC of Trypanosoma brucei. The conserved peptide is proposed to play a role in the function of these enzymes.

Interactions among DUI offender characteristics and traditional intervention modalities: a long-term recidivism follow-up.

Using long-term DUI (Driving Under the Influence of Alcohol) arrest recidivism data from a controlled study of DUI intervention effectiveness, interactions among DUI interventions, age, race, education, and alcohol severity were estimated using logit analysis. Data were collected in a 9-year follow-up study of the Mississippi DUI Probation Project. The effects of short-term interventions (alcohol education schools for low alcohol severity offenders and structured group interventions for high alcohol severity offenders) were specified by educational level. Short-term rehabilitation was modestly effective for those with less than 12 years of education, but less effective or detrimental for the more highly educated. The effects of probation were specified by age and education, being more effective for those under 30 years and 55 years or older than for the middle age group. Probation was most effective for well-educated older (55+) offenders. An analysis of the under 30 years group also suggested that probation was especially effective for young well-educated Minority offenders.