TCRBV3S1 and TCRBV18 gene segment polymorphisms in Brazilian Caucasoid and Black populations.

The T-cell receptor (TCR) repertoire plays an important role in shaping specific immune responses. Genetic polymorphisms at the TCR locus, in both constant and variable regions, seem to represent an important mechanism for generating inter-individual and inter-population differences. Considering the scarcity of immune parameters characterized for normal human populations, we decided to determine the frequency of two TCRBV polymorphisms (located in the TCRBV3S1 and TCRBV18 gene segments) in two ethnically distinct groups of the general Brazilian population. Both polymorphisms are related to the expression of these segments at the T-cell surface and can consequently modulate the T-cell repertoire, potentially modifying the capacity of a given individual to develop an immune response. These DNA polymorphisms were analysed in material obtained from adult, normal South-American Caucasoid and Black individuals. A total of 139 individuals were analysed for the TCRBV3S1 and 141 for the TCRBV18 gene segment polymorphisms. The data indicated statistically significant differences in allelic frequencies for the two ethnic groups analysed, suggesting that any correlation between TCR usage or T-cell repertoire and development of a given disease should take in account the ethnic origin of the population studied.     

The precision of positron emission tomography: theory and measurement

The limits of quantitation with positron emission tomography (PET) are examined with respect to the noise propagation resulting from radioactive decay and other sources of random error. Theoretical methods for evaluating the statistical error have been devised but seldom applied to experimental data obtained on human subjects. This paper extends the analysis in several ways: (1) A Monte Carlo method is described for tracking the propagation of statistical error through the analysis of in vivo measurements; (2) Experimental data, obtained in phantoms, validating the Monte Carlo method and other methods are presented; (3) A difference in activation paradigm, performed on regional CBF (rCBF) data from five human subjects, was analyzed on 1.6-cm diameter regions of interest to determine the mean fractional statistical error in PET tissue concentration and in rCBF before and after stereotactic transformation; and (4) A linear statistical model and calculations of the various statistical errors were used to estimate the magnitude of the subject-specific fluctuations under various conditions. In this specific example, the root mean squared (RMS) noise in flow measurements was about three times higher than the RMS noise in the concentration measurements. In addition, the total random error was almost equally partitioned between statistical error and random fluctuations due to all other sources.     

Regulatory properties of brain glutamate decarboxylase (GAD): the apoenzyme of GAD is present principally as the smaller of two molecular forms of GAD in brain

The apoenzyme of glutamate decarboxylase [enzyme without bound cofactor, pyridoxal 5'-phosphate (pyridoxal-P)] serves as a reservoir of inactive glutamate decarboxylase (GAD) that can be activated when additional GABA synthesis is required. We have investigated which of two molecular forms of GAD is present as apoenzyme in synaptosomes and in cortex, caudate nucleus, hippocampus, and cerebellum of rat brain. Endogenous glutamate apodecarboxylase (apoGAD) was labeled by incubating extracts of synaptosomes or punches of each region with 32P-pyridoxal-P, followed by reduction with NaBH4, to link covalently the 32P-pyridoxal-P to GAD. Proteins were separated by SDS-PAGE. Punches from all four brain regions and forebrain synaptosomes contained two forms of GAD with apparent Mrs of 63 and 65 kDa as identified by immunoblotting with four antiGAD sera. Punches and synaptosomes contained a major 32P-pyridoxal-P-labeled band with an apparent Mr of 63 kDa that was stained on immunoblots by the antiGAD serum 1440 and the monoclonal antibody GAD-6, and a minor labeled band at 65 kDa that was stained by the 1440, 6799, and K2 antisera. Synaptosomes contained remarkably few other strongly labeled proteins, but punches contained several other labeled bands. Three additional lines of evidence indicate that the labeled 63-kDa protein is apoGAD: (1) it was purified by immunoaffinity chromatography with the GAD-1 monoclonal antibody; (2) it yielded one major labeled peptide when digested with chymotrypsin, and that peptide appeared identical in peptide-mapping experiments to the labeled active-site peptide isolated from chromatographically prepared rat brain GAD; and (3) its labeling was selectively blocked by 4-deoxypyridoxine 5'-phosphate, a competitive inhibitor of the binding of pyridoxal-P to GAD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spectral analysis of the electroencephalogram in neonatal rats chronically treated with the NMDA antagonist MK-801.

In order to study the involvement of NMDA-receptor activation in brain development, rat pups were chronically treated with the non-competitive NMDA antagonist MK-801 during the neonatal period. We recorded the cortical EEG at various vigilance states throughout the treatment period. Spectral analysis of the EEG showed reduced power in the delta (delta) frequency range (1.5-4 Hz) during quiet sleep and less power in the theta (theta) range (4-7 Hz) during REM-sleep in MK-801 animals than in controls. No significant differences were found for the total time spent in each of the different vigilance states. We conclude that chronic MK-801 treatment probably causes a developmental retardation in state-related brain activities.     

Concurrent review of the duration of antimicrobial prophylaxis in surgery.

The administration of prophylactic antibiotics in surgery is appropriate for many patients. Data have shown extending the duration of prophylaxis beyond 48 hours does not lower the rate of postoperative-infection. The purpose of this project was to concurrently assess the duration of prophylactic antibiotic use. A total of 95 patients were monitored over 3 weeks. Eighty patients (84.2%) received antimicrobial therapy. In 23 of these patients (28.75%) the duration of antibiotic administration was longer than 2 days without clinical or microbiological evidence of infection. In 5 other patients only postoperative antibiotics were prescribed. The cost difference between the actual duration of antibiotic administration and 2 days of the same regimen was +1,364.58. Extrapolating for one year, it can be estimated that antibiotic costs could be reduced about +23,600. Pharmacists can focus on the duration of antibiotic prophylaxis as a cost containment measure.