Acyclovir (ACV) has shown efficacy in the prophylactic suppression of human cytomegalovirus (HCMV) reactivation in immunocompromised renal transplant patients without the toxicity associated with ganciclovir (GCV). The HCMV UL97 gene product, a protein kinase, is responsible for the phosphorylation of GCV in HCMV-infected cells. This report provides evidence for the phosphorylation of ACV by UL...

Generalized cross validation (GCV) is one of the most important approaches used to estimate parameters in the context of inverse problems and regularization techniques. A notable example is the determination of the smoothness parameter in splines. When the data are generated by a state space model, like in the spline case, efficient algorithms are available to evaluate the GCV score with comple...

Cytomegalovirus (CMV) replicates rapidly in its human host with a doubling time of approximately 1 day. Using simple mathematical models we show that the efficacy of the anti-CMV drug ganciclovir (GCV) against wild-type strains is 91.5% [95% confidence interval (CI) 89-94%] when given i.v. (5 mg/kg twice a day) but only 46.5% (95% CI 45-47.5%) when given orally (1 g three times a day) whereas t...

Thirteen point mutations targeting predicted domains conserved in homologous protein kinases were introduced into the UL97 coding region of the human cytomegalovirus. All mutagenized proteins were expressed in cells infected with recombinant vaccinia viruses (rVV). Several mutations drastically reduced ganciclovir (GCV) phosphorylation. Mutations at amino acids G340, A442, L446, and F523 result...

A new technique is proposed to estimate the robust continuous observation densities of hidden Markov model (HMM) for improving the performance of speaker-independent (SI) automatic speech recognition system. First, a scheme of generalized common vector (GCV), which originated from the common vector approach (CVA), is proposed. The objective of this scheme is to extract a robust speech feature o...

It has been noticed by several authors that there is a small but non-zero probability that the GCV estimate 2 of the smoothing parameter in spline and related smoothing problems will he extremely small, leading to gross undersmoothing. We obtain an upper bound to the probability that the GCV function, whose minimizer provides ,~, has a (possibly local) minimum at 0. This upper bound goes to 0 e...

images of VPM-PET (left), Ktrans from ETM (middle), and EFPM (right). Choroid Plexus (thick arrow) and pituitary gland (arrow heads) are clearly depicted. The GCV shows high Ktrans on the maps of ETM, rendered with red color, but not EFPM. Note that GCV and other large vessels were not found on the PET image render blue representing lowest intensity. Figure 2. Axial (1st row) and sagittal (2nd ...

Herpes simplex virus thymidine kinase (HSV-tk)/ganciclovir (GCV) viral-directed enzyme prodrug gene therapy causes potent, tumor-selective cytotoxicity in animal models in which HSV-tk gene transduction is limited to a minority of tumor cells. The passage of toxic molecules from HSV-tk+ cells to neighboring HSV-tk- cells during GCV therapy is one mechanism that may account for this "bystander" ...

Most ganciclovir (GCV)-resistant cytomegalovirus (CMV) isolates contain UL97 gene mutations at codon 460 or 520 or between codons 590 and 607, where an increasing variety of mutations have been detected, including deletions. To determine their phenotypic effect, 9 UL97 mutations not previously studied were transferred to drug-sensitive laboratory CMV strains that contained unique restriction si...

Cytomegalovirus (CMV) infection after renal transplantation is a problem of increasing concern resulting in significant morbidity and mortality. Widespread use of ganciclovir (GCV) and valganciclovir (VGCV) may cause an increase of CMV resistance to these first line drugs. Other treatment options are sparse and often complicated by adverse events, namely nephrotoxicity associated with foscarnet...