SL25.1131 [3(S),3a(S)-3-methoxymethyl-7-[4,4,4-trifluorobutoxy]-3,3a,4,5-tetrahydro-1,3-oxazolo[3,4-a]quinolin-1-one], a new, reversible, and mixed inhibitor of monoamine oxidase-A and monoamine oxidase-B: biochemical and behavioral profile.

SL25.1131 [3(S),3a(S)-3-methoxymethyl-7-[4,4,4-trifluorobutoxy]-3,3a,4,5-tetrahydro-1,3-oxazolo[3,4-a]quinolin-1-one] is a new, nonselective, and reversible monoamine oxidase (MAO) inhibitor, belonging to a oxazoloquinolinone series. In vitro studies showed that SL25.1131 inhibits rat brain MAO-A and MAO-B with IC50 values of 6.7 and 16.8 nM and substrate-dependent Ki values of 3.3 and 4.2 nM, respectively. In ex vivo conditions, the oral administration of SL25.1131 induced a dose-dependent inhibition of MAO-A and MAO-B activities in the rat brain with ED50 values of 0.67 and 0.52 mg/kg, respectively. In the rat brain, duodenum, and liver, the inhibition of MAO-A and MAO-B by SL25.1131 (3.5 mg/kg p.o.) was reversible, and the recovery of MAO-A and MAO-B activities was complete 16 h after administration. SL25.1131 (3.5 mg/kg p.o.) increased tissue levels of dopamine (DA), norepinephrine, and 5-hydroxytryptamine and decreased levels of their deaminated metabolites 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindolacetic acid. In mice, SL25.1131 induced a dose-dependent potentiation of 5-hydroxytryptophan-induced tremors and phenylethylamine-induced stereotypies with ED50 values of 0.60 and 2.8 mg/kg p.o., respectively. SL25.1131 was able to reestablish normal striatal dopaminergic tone and locomotor activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mice. In addition, when coadministered with L-DOPA, SL25.1131 increased the available DA in the striatum and the duration of L-DOPA-induced hyperactivity. The duration of the effect of L-DOPA on circling behavior in 6-hydroxydopamine-lesioned rats was also increased. The neurochemical profile of SL25.1131 demonstrates that this compound is a mixed, potent, and reversible MAO-A/B inhibitor in vitro, in vivo, and ex vivo. SL25.1131 has therapeutic potential as a symptomatic treatment during the early phase of Parkinson's disease and as an adjunct to L-DOPA therapy during the early and late phases of the disease.

Battery powered BION FES network.

The Alfred Mann Foundation is completing development of a coordinated network of BION microstimulator/sensor (hereinafter implant) that has broad stimulating, sensing and communication capabilities. The network consists of a master control unit (MCU) in communication with a group of BION implants. Each implant is powered by a custom lithium-ion rechargeable 10 mW-hr battery. The charging, discharging, safety, stimulating, sensing, and communication circuits are designed to be highly efficient to minimize energy use and maximize battery life and time between charges. The stimulator can be programmed to deliver pulses in any value in the following range: 5 microA to 20 mA in 3.3% constant current steps, 7 micros to 2000 micros in 7 micros pulse width steps, and 1 to 4000 Hz in frequency. The preamp voltage sensor covers the range 10 microV to 1.0 V with bandpass filtering and several forms of data analysis. The implant also contains sensors that can read out pressure, temperature, DC magnetic field, and distance (via a low frequency magnetic field) up to 20 cm between any two BION implants. The MCU contains a microprocessor, user interface, two-way communication system, and a rechargeable battery. The MCU can command and interrogate in excess of 800 BlON implants every 10 ms, i.e., 100 times a second.

Is time since hip fracture influencing the discrimination between fractured and nonfractured subjects as assessed at the calcaneum by three technologically different quantitative ultrasound devices?

Because quantitative ultrasound (QUS) instruments from different manufacturers have significant technical differences, it is difficult to assess whether all of them can discriminate similarly between osteoporotic fractures and age-matched controls. Thus, to avoid any bias, reliable comparative assessment of the QUS devices should be carried out on the same population. Few studies have fulfilled this condition. Another source of variability in cross-sectional studies in which fractured and nonfractured subjects are compared is the time since osteoporotic fracture. Our study evaluated the ability of three calcaneal QUS devices to discriminate patients with osteoporotic hip fracture from control subjects, using the same population. In addition, a subset of patients was re-measured about 9 months after the hip replacement surgery to check how the time since fracture affects the discriminatory ability of the different QUS devices. Fifty postmenopausal hip-fractured patients and 46 postmenopausal age-matched controls were included in this study and measured on three QUS devices, as well as 50 young healthy controls to calculate the T-score. Odds ratio results showed that a decrease in UBIS trade mark BUA of 1 SD was associated with a significant increase in fracture risk (odds ratio adjusted = 2.30) comparable with Sahara broadband ultrasound attenuation (BUA) (OR adj. = 2.30), and Achilles BUA (OR adj. = 3.5). However, given the large overlap between the 95% intervals of each OR and for the areas under ROC curves, no significant difference was found between them. In the subset of 15 hip-fractured subjects, no significant differences were found between ultrasound parameters of the first visit and 9 months after except for the heel width (soft tissue variation). Odds ratio and areas under the curve (AUC) tend to increase from visit 1 to 2 for the BUA and decrease substantially for the SOS for all but the Lunar Achilles+. Nonsignificant correlation was found between the absolute difference of the ultrasound parameters measured at the two visits and the time since fracture, except for the Sahara SOS (r = 0.45; P < 0.04). In conclusion, no significant differences between QUS technologies were observed in their positive and significant ability to discriminate hip-fractured patient from controls. However, this statement is shadowed when taking into account the time since fracture which seems to negatively influence results obtained on dry versus wet QUS systems. As a result, it is advisable that such parameters would be taken into account when designing a study aimed to demonstrate the discriminatory ability of heel ultrasound between normal and hip-fractured patients.

Comparing pediatric intentional injury surveillance data with data from publicly available sources: consequences for a public health response to violence.

OBJECTIVE: A hospital based intentional injury surveillance system for youth (aged 3-18) was compared with other publicly available sources of information on youth violence. The comparison addressed whether locally conducted surveillance provides data that are sufficiently more complete, detailed, and timely that clinicians and public health practitioners interested in youth violence prevention would find surveillance worth conducting. SETTING: The Boston Emergency Department Surveillance (BEDS) project was conducted at Boston Medical Center and the Children's Hospital, Boston. METHOD: MEDLINE and other databases were searched for data sources that report separate data for youth and data on intentional injury. Sources that met these criteria (one national and three local) were then compared with BEDS data. Comparisons were made in the following categories: age, gender, victim-offender relationship, injury circumstance, geographic location, weapon rates, and violent injury rates. RESULTS: Of 14 sources dealing with violence, only four met inclusion criteria. Each source provided useful breakdowns for age and gender; however, only the BEDS data were able to demonstrate that 32.6% of intentional injuries occurred among youth aged 12 and under. Comparison data sources provided less detail regarding the victim-offender relationship, injury circumstance, and weapon use. Comparison of violent injury rates showed the difficulties for practitioners estimating intentional injury from sources based on arrest data, crime victim data, or weapon related injury. CONCLUSIONS: Comparison suggests that surveillance is more complete, detailed, and timely than publicly available sources of data. Clinicians and public health practitioners should consider developing similar systems.

Study of fossil tracks due to 50 < or = Z < or = 92 galactic cosmic ray nuclei in meteoritic crystals: results and perspectives.

A new approach to the problem of investigation of charge and energy spectra of ultra heavy Galactic cosmic ray nuclei, based on fossil track study of extraterrestrial olivine crystals has been developed. The results of an investigation of ultra heavy Galactic cosmic ray nuclei (Z=50-92) in meteoritic olivine crystals are presented. The technique was based on calibration of olivine crystals with accelerated Xe, Au, Pb and U ions and well-controlled partial annealing of "fresh" and "fossil" tracks. It allows us to determine the charge spectra and abundances of cosmic ray nuclei based on fossil track length study in meteoritic and Moon crystals. The comparative studies of the spectra of "fossil' tracks and tracks due to 208Pb and 238U nuclei have shown that the group of 210 micrometers "fossil" tracks, first observed in 1980 at JINR is due to Th-U nuclei-products of recent r-process nucleosynthesis in our Galaxy. The method in principle allows one to resolve Pt-Pb peaks in fossil tracks, to establish the upper limit of the abundance of Z>110 nuclei in the Galactic cosmic rays at the level < or = 10(-3) to the abundance of actinide nuclei and to get information on the history of Z>50 cosmic ray nuclei in time interval up to 220 M.Y.

Neuroprotective effect of eliprodil: attenuation of a conditioned freezing deficit induced by traumatic injury of the right parietal cortex in the rat.

We have previously demonstrated that a lateral fluid percussion-induced traumatic lesion of the right parietal cortex can lead to a deficit in a conditioned freezing response and that this deficit can be attenuated by both pre- and postlesion administration of the NMDA receptor antagonist dizocilpine. In the present study, we investigated the effects of eliprodil, a noncompetitive NMDA receptor antagonist acting at the polyamine modulatory site, which also acts as a Ca2+ channel blocker, on the trauma-induced conditioned freezing deficit. Eliprodil produced a 50% reduction in this deficit when administered as three 1 mg/kg injections i.v. at 15 min, 6 h, and 24 h following the lesion. Approximately the same degree of protection was afforded when 2 x 1.5 mg/kg were administered 6 and 24 h and equally at 12 and 24 h after surgery (56% and 59%, respectively). A single treatment (3 mg/kg) at 24 h was ineffective against the deficit. The protection afforded with treatment at 6 and 24 h after lesion was dose dependent, with a minimal active dose of 2 x 0.75 mg/kg. These data complement those previously published on the ability of eliprodil to reduce lesion volume following traumatic brain injury and show, in addition, that the neuroprotective effect has functional consequences.

Saccades to large coloured targets stepping in open fields.

Subjects tracked a 2.3 deg target that stepped 5 deg, in a randomly chosen direction, each time it was foveated. Targets were coloured patches that were fairly close to white; in some cases precise matches ensured equiluminosity with the background. Viewing conditions provided good colour rendering and neutral colour adaptation. Pale colours were surprisingly well tracked. Multiple regressions showed that the colour and spatial characteristics of the target are important determinants of a primary saccade's latency. Significant factors included target size, achromatic contrast, tritanopic purity difference, and chromatic saturation. Colour-normal subjects always responded more slowly to yellow or blue targets which a deuteranomalous subject tracked quite well. Severely blurring the target had a consistent minor effect.

Origin and metamorphic redistribution of silicon, chromium, and phosphorus in the metal of chondrites.

Chromium, silicon, and phosphorus concentrations of 0.1 to 1 percent by weight are common in metal grains in the least metamorphosed ordinary and carbonaceous chondrites. These concentrations are fairly uniform within single chondrules (but different from chondrule to chondrule) and are inversely correlated with the fayalite concentrations of the chondrule olivines. This relation shows that these chromium, silicon, and phosphorus concentrations could not have been established by condensation or equilibration in the solar nebula but are the result of metal-silicate equilibration within chondrules. Two generations of inclusions made by the exsolution of those elements have been identified: One formed during chondrule cooling and the other formed during metamorphism. The distribution and composition of the latter in type 3 to type 5 chondrites are consistent with increasing metamorphism relative to type 2 and type 3.0 material.

Agrammatism in sentence production without comprehension deficits: reduced availability of syntactic structures and/or of grammatical morphemes? A case study.

A French-speaking patient with Broca's aphasia--following a left-hemisphere lesion involving the sylvian region but sparing Broca's area--is presented. Like G. Miceli, A. Mazzuchi, L. Menn, and H. Goodglass's (1983, Brain and Language, 19, 65-97) case 2, this patient produces agrammatic speech in the absence of any comprehension deficit. Unlike Miceli's patient, though, agrammatic speech can be observed in all sentence production tasks (from spontaneous speech to repetition, oral reading, and writing) whereas production of individual words--be they open class or closed class--is almost always intact. On the basis of extensive (psycho)linguistic testing, it is argued that this patient's deficit is not central and not crucially syntactic (at least) at the level of knowledge but seems to disrupt specifically those (automatic?) processes responsible for both retrieval and production of free-standing grammatical morphemes whenever they have to be inserted into phrases and sentences.

Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors.

Three kinds of improvements have been introduced into the M13-based cloning systems. (1) New Escherichia coli host strains have been constructed for the E. coli bacteriophage M13 and the high-copy-number pUC-plasmid cloning vectors. Mutations introduced into these strains improve cloning of unmodified DNA and of repetitive sequences. A new suppressorless strain facilitates the cloning of selected recombinants. (2) The complete nucleotide sequences of the M13mp and pUC vectors have been compiled from a number of sources, including the sequencing of selected segments. The M13mp18 sequence is revised to include the G-to-T substitution in its gene II at position 6 125 bp (in M13) or 6967 bp in M13mp18. (3) M13 clones suitable for sequencing have been obtained by a new method of generating unidirectional progressive deletions from the polycloning site using exonucleases HI and VII.

Purified lexA protein is a repressor of the recA and lexA genes.

Escherichia coli shows a pleiotropic response (the SOS response) to treatments that damage DNA or inhibit DNA replication. Previous evidence has suggested that the product of the lexA gene is involved in regulating the SOS response, perhaps as a repressor, and that it is sensitive to the recA protease. We show here that lexA protein is a repressor of at least two genes, recA and lexA. Purified protein bound specifically to the regulatory regions of the two genes, as judged by DNase I protection experiments, and it specifically inhibited in vitro transcription of both genes. The binding sites in recA and lexA were found to be about 20 base pairs (bp) and 40 bp long, respectively. The 40-bp sequence in lexA was composed of two adjacent 20-bp sequences, which had considerable homology to one another and to the corresponding recA sequence. These 20-bp sequences, which we term "SOS boxes," show considerable inverted repeat structure as well. These features suggest that each box represents a single repressor binding site. Finally, we found that purified lexA protein was a substrate for the recA protease in a reaction requiring ATP or an analogue, adenosine 5'-[gamma-thio]triphosphate, and denatured DNA.