Glutamyl-gamma-boronate inhibitors of bacterial Glu-tRNA(Gln) amidotransferase.

Analogues of glutamyl-gamma-boronate (1) were synthesized as mechanism-based inhibitors of bacterial Glu-tRNA(Gln) amidotransferase (Glu-AdT) and were designed to engage a putative catalytic serine nucleophile required for the glutaminase activity of the enzyme. Although 1 provides potent enzyme inhibition, structure-activity studies revealed a narrow range of tolerated chemical changes that maintained activity. Nonetheless, growth inhibition of organisms that require Glu-AdT by the most potent enzyme inhibitors appears to validate mechanism-based inhibitor design of Glu-AdT as an approach to antimicrobial development.

Vascular endothelial growth factor in porcine coronary arteries following balloon angioplasty.

The present study was a preliminary inquiry into the presence of vascular endothelial growth factor (VEGF) in a model of coronary artery response to injury. We examined domestic pigs who had received a diet enriched in saturated fat and cholesterol and undergone balloon angioplasty of one or more coronary arteries. Immunohistochemical analysis of the coronary arteries 2 months after injury revealed the presence of VEGF distributed throughout the media and neointima of the angioplasty lesions and in association with blood vessels in the adventitia and those vessels growing into the base of the neointima. VEGF was also detected in areas of dietary-induced intimal proliferation. This study provided the first immunochemical demonstration of VEGF occuring naturally in a pig model of coronary response to injury.

Internal cardioversion in two patients with atrial fibrillation refractory to external cardioversion.

A 26-year-old man underwent an electrophysiological study for evaluation of a history of congenital heart disease, presyncope, and wide complex tachycardia. During the study the patient developed sustained atrial fibrillation with a rapid ventricular response. A 17-year-old man with a history of sick sinus syndrome developed sustained atrial fibrillation. Both patients failed four attempts at external cardioversion with a maximum delivered energy of 360 J. Low energy cardioversion was successful in both patients using biphasic waveforms and internal transvenous defibrillation electrodes. Internal cardioversion using a transvenous electrode system can be successful in patients with atrial fibrillation refractory to external cardioversion.

Magnesium reversal of digoxin-facilitated ventricular rate during atrial fibrillation in the Wolff-Parkinson-White syndrome.

In patients with Wolff-Parkinson-White syndrome and atrial fibrillation, digoxin may increase the ventricular rate by facilitating conduction over the accessory pathway either directly by enhancing accessory pathway conduction and/or indirectly as a consequence of its effect on atrioventricular nodal conduction. Two cases are presented in which the intravenous administration of magnesium sulfate reversed digoxin facilitation of the ventricular rate to atrial fibrillation in the Wolff-Parkinson-White syndrome.

Characterization and rapid analysis of the highly polymorphic VNTR locus D4S125 (YNZ32), closely linked to the Huntington disease gene.

The highly polymorphic VNTR locus pYNZ32 has been more extensively characterized, and its analysis converted to a rapid PCR-based format. DNA sequencing in the areas within and flanking the repeated segment allowed the design of specific amplification primers. The repeated region of pYNZ32 consists of an imperfectly duplicated 27-bp motif, 16 bases of which are more highly conserved. Allelic products from PCR amplification were resolved into nine different size classes ranging from approximately 1400 to 2200 bp. Additional polymorphism was revealed when the amplified products were analyzed by restriction enzyme digestion. Both the overall size variation and the internal sequence polymorphism were used to determine a heterozygosity value of 86% for YNZ32 in 50 unrelated individuals. The rapid analysis and improved resolution of amplified alleles on agarose gels, and the internal variability within YNZ32, increase its diagnostic utility as a VNTR and as a linkage marker for the nearby Huntington disease gene.

Characterization and rapid diagnostic analysis of DNA polymorphisms closely linked to the cystic fibrosis locus.

Six genetic polymorphisms, closely linked to the cystic fibrosis gene and useful in clinical linkage analysis, have been characterized and converted to a more rapid form of assay. Sequences flanking the metD (Ban I), metH (Msp I), XV-2c (Taq I), KM.19 (Pst I), MP6d-9 (Msp I), and J3.11 (Msp I) polymorphic restriction sites have been determined and used to design specific polymerase chain reaction (PCR) amplification primers and allele-specific oligonucleotide probes. All six of these polymorphisms were found to involve single-base alterations, and the XV-2c polymorphism was found to lie within an Alu repeat segment. These PCR-based tests, in conjunction with the CS.7 (Hha I) assay described elsewhere (Stanier P et al. Hum Genet 1988;80:309-10; Williams C et al. Lancet 1988;ii:102-3), provide a convenient, rapid, and reliable method of haplotype and linkage analysis, clinically useful in those situations where direct detection of mutations is not possible.

Systematic errors in emission cross sections arising in the analysis of laboratory beam measurements.

A technique for obtaining emission cross sections in laboratory beam studies is presented, including effects on the cross section due to polarization of the emitted light. Systematic analytical errors arising from optical problems are analyzed and evaluated for a typical spectral feature. The primary sources of error are shown to arise from the particular geometry used in the optical measurements, the variation of the calibrating light source over the bandwidth of the emission feature, and the variation of the responsivity of the optical system over the bandwidth.

The calibration of scanning monochromators for the measurement of absolute irradiance.

Certain approximations commonly used in the absolute calibration of a scanning monochromator are examined in terms of the response of the instrument to a monochromatic input. The absolute irradiance due to any spectral feature in the neighborhood of lambda(0) is commonly computed from the expression W = AB(lambda(0))/H(lambda(0)) where A is the area of the spectral feature as recorded by the monochromator output trace, B(lambda) is the spectral irradiance of a standard source, and H(lambda) is the response of the monochromator to B(lambda) when the monochromator corresponds to wavelength lambda. As an example, approximations used in justifying such calculations are examined and applied to an Ebert 0.5-m monochromator. For the case chosen, the approximation is shown to be valid to an accuracy of 1.5% to 2%, depending upon assumptions made in the calculation. It is found that the most serious error for this example is introduced by changes in the sensitivity of the monochromator over a wavelength interval comparable with that of the spectral feature under investigation. A second source of error is found to be the change in the irradiance of the standard source over a wavelength interval comparable to the instrument resolving power.