Biomedical subjects

Amita Patel

Publications and source records attributed to Amita Patel.

5 recordsLinked to original sources

PubMed2005

Development of herpes simplex virus disease in patients who are receiving cidofovir.

BACKGROUND: Cidofovir is a nucleotide analogue with antiviral activity against a wide range of DNA viruses, including herpes simplex virus (HSV). In vitro resistance to cidofovir has been reported with use of laboratory HSV strains; clinical failure of cidofovir therapy for HSV disease has also been reported with an isolate that was susceptible by in vitro testing. PATIENTS AND METHODS: Three patients with HSV disease that was unresponsive to cidofovir therapy had viral isolates obtained and stored; the isolates were analyzed for antiviral susceptibility by an antigen reduction assay (ARA). PCR cloning and automated sequencing were performed for isolates that displayed in vitro resistance. Mutations were identified by comparison with the appropriate HSV consensus sequence. RESULTS: An HSV type 2 (HSV-2) isolate recovered from patient 2 displayed in vitro cidofovir resistance with an inhibitory concentration of 50% (IC50) of 13.06 microg/mL. HSV type 1 isolates recovered from patients 1 and 3 had elevated IC50s to cidofovir (7.32 and 8.23 microg/mL, respectively); however, these isolates did not meet the cutoff point for resistance according to the ARA. Sequencing of a cidofovir-resistant HSV-2 isolate revealed several DNA polymerase mutations that had not been previously described during in vitro resistance selection. CONCLUSIONS: To our knowledge, this is the first report of cidofovir resistance in HSV developing in vivo. The 3 sequenced clones all contained mutations truncating the pol C' end, suggesting that this region may be critical for cidofovir antiviral activity. In addition, the presence of multiple mutations suggests that the altered DNA polymerase of cidofovir-resistant virus may have introduced additional mutations into the viral genome. Introduction of the mutations identified in wild-type HSV strains is needed before the resistance phenotype can be definitively associated with any of the mutations found. Additional studies are needed to delineate the mechanisms of cidofovir resistance in HSV.

Antiviral Agents↗

PubMed2005

Performance assessment of a zeolite treatment wall for removing Sr-90 from groundwater.

Laboratory and modeling studies were conducted to assess the potential performance of a permeable reactive barrier constructed of a natural zeolite material at the West Valley Demonstration Project in western New York State. The results of laboratory column tests indicated that the barrier material would be effective at removing strontium from groundwater under natural gradient conditions. Two one-dimensional contaminant transport models were developed to interpret the data. A single-solute retardation factor model provided good agreement with the column test data, but time-consuming extraction and analysis of the zeolite material was required to parameterize the model. A preliminary six-solute model was also developed based on the assumption of competitive cation exchange as the primary removal mechanism. Both models yielded similar predictions of the long-term performance of the barrier, but the cation exchange model predicted higher effluent concentrations during the first 1000 pore volumes of operation. The cation exchange framework has several advantages, including the ability to calibrate the model using only data from column effluent samples, and the ability to account for site-specific differences in the groundwater cation composition. However, additional laboratory work is needed to develop a suitably robust model.

Ion Exchange↗

PubMed2004

Activation of CRABS CLAW in the Nectaries and Carpels of Arabidopsis.

CRABS CLAW (CRC), a member of the YABBY gene family, is required for nectary and carpel development. To further understand CRC regulation in Arabidopsis thaliana, we performed phylogenetic footprinting analyses of 5' upstream regions of CRC orthologs from three Brassicaceae species, including Arabidopsis. Phylogenetic footprinting efficiently identified functionally important regulatory regions (modules), indicating that CRC expression is regulated by a combination of positive and negative regulatory elements in the modules. Within the conserved modules, we identified putative binding sites of LEAFY and MADS box proteins, and functional in vivo analyses revealed their importance for CRC expression. Both expression and genetic studies demonstrate that potential binding sites for MADS box proteins within the conserved regions are functionally significant for the transcriptional regulation of CRC in nectaries. We propose that in wild-type flowers, a combination of floral homeotic gene activities, specifically the B class genes APETALA3 and PISTILLATA and the C class gene AGAMOUS act redundantly with each other and in combination with SEPALLATA genes to activate CRC in the nectaries and carpels. In the absence of B and C class gene activities, other genes such as SHATTERPROOF1/2 can substitute if they are ectopically expressed, as in an A class mutant background (apetala2). These MADS box proteins may provide general floral factors that must work in conjunction with specific factors in the activation of CRC in the nectaries and carpels.

AGAMOUS Protein, Arabidopsis↗

PubMed2003

Development of resistance to acyclovir during chronic infection with the Oka vaccine strain of varicella-zoster virus, in an immunosuppressed child.

A 1-year-old boy was vaccinated with the Oka strain of varicella just prior to the discovery of a tumor that required intensive antitumor therapy. Three months later he developed herpes zoster, which developed into chronic verrucous lesions that were refractory to treatment with acyclovir and which subsequently disseminated. DNA from a biopsy specimen of a chronic herpes-zoster lesion indicated that the Oka vaccine strain of the the virus caused this severe complication. Analysis of this viral DNA demonstrated a mutation in the viral thymidine kinase gene. Plasmids containing this altered gene were unable to produce functional thymidine kinase in an in vitro translation system. The presence of this mutation would explain the clinical resistance to acyclovir. This is the first report of Oka-strain varicella virus causing severe disease after reactivation and of resistance to acyclovir during an infection caused by this virus.

Abdominal Neoplasms↗

PubMedDate not supplied

An HSV-1 chimeric containing HSV-2 latency associated transcript (LAT) sequences has significantly reduced adrenergic reactivation in the rabbit eye model.

PURPOSE: Both HSV-1 and HSV-2 express LAT during viral latency. Previous studies indicated that deletion of either LAT impairs viral reactivation from latency, but that the HSV-1 LAT confers the ability to reactivate efficiently from trigeminal ganglia onto HSV-2. We sought to determine whether the HSV-2 LAT could function in the context of HSV-1. METHODS: A chimeric HSV-1 that expresses the HSV-2 LAT in place of both copies of its own LAT was constructed. A rescuant virus, in which the wild-type genotype was restored, was also constructed to demonstrate that any phenotypic differences between the mutant virus and wild-type virus were due to the introduced mutations rather than to inadvertent mutations elsewhere in the virus. All viruses were tested in vitro and in vivo (via inoculation of rabbit eyes and induction of reactivation via iontophoresis of epinephrine) to determine the ability of the HSV-2 LAT to substitute for the HSV-1 LAT during acute infection and reactivation from latency. RESULTS: Substitution of the HSV-2 LAT for the HSV-1 LAT had no effect on acute replication or on the ability of the virus to cause disease in the rabbit ocular model. The ability of the mutant virus to reactivate from latency was substantially impaired relative to wild-type HSV-1. CONCLUSIONS: The HSV-2 LAT cannot substitute for the HSV-1 LAT in promoting reactivation from HSV-1 latency from rabbit trigeminal ganglia. This is consistent with the LAT being the major determinant of site-specific HSV reactivation.

Animals↗