Impact of Ethylene Glycol Toxicity on Donor Organ Viability: A Case Report.

Using kidneys from deceased donors whose demise was secondary to ethylene glycol (EG) toxicity requires considerable thought and planning. The exact impact that kidneys from these donors could have is unclear. The shortage of viable organs and growing wait list mortality should lead us to consider these allografts as potential life-saving transplants. Because it is crucial for the transplant community to use every available allograft, we need to develop processes that optimize each possible scenario. This article is a discussion of the viability of kidneys from a donor with EG-induced brain death and a proposed algorithm for encouraging the use of renal allografts after EG toxicity.

The activation domain of herpesvirus saimiri R protein interacts with the TATA-binding protein.

The herpesvirus saimiri open reading frame (ORF) 50 produces two transcripts. The first is spliced, contains a single intron, and is detected at early times during the productive cycle, whereas the second is expressed later and is produced from a promoter within the second exon. Analysis of their gene products has shown that they function as sequence specific transactivators. In this report, we demonstrate that the carboxy terminus of ORF 50b contains an activation domain which is essential for transactivation. This domain contains positionally conserved hydrophobic residues found in a number of activation domains, including the herpes simplex virus VP16 and the Epstein-Barr virus R proteins. Mutational analysis of this domain demonstrates that these conserved hydrophobic residues are essential for ORF 50 transactivation capability. Furthermore, this domain is required for the interaction between the ORF 50 proteins and the basal transcription factor TATA-binding protein.

Assessment of Herpesvirus saimiri as a potential human gene therapy vector.

Herpesvirus saimiri has characteristics that make it amenable to development as a gene therapy vector. The viral genome is thought to be capable of accommodating large quantities of heterologous DNA while the virus itself can infect many different cell types. Virus infection has been shown in many cases to be persistent by virtue of episomal maintenance in the target cell. In this article we examine the ability of nonselectable recombinant viruses expressing the beta-galactosidase gene product to infect a variety of human cells and demonstrate that this virus could be developed as an alternative hematopoietic stem cell gene therapy vector. In contrast to earlier observations, we demonstrate by a number of methods that the virus has the ability to replicate in many human cell types, suggesting the need for the development of a disabled virus for use as a gene therapy vector.

Autopsy findings in a severely affected infant with a 2q terminal deletion.

We describe a 37-week gestation female infant who was born with a terminal 2q deletion. Both of her parents had normal chromosomes. This infant had multiple anomalies, including hypertelorism, short palpebral fissures, microphthalmia, cleft lip/cleft palate, and abnormal ears. Autopsy documented Dandy-Walker malformation with severe hydrocephalus, aortopulmonary window, secundum atrial septal defect, duodenal atresia, incomplete rotation of the bowel, gonadal dysgenesis, uterus didelphys, and musculoskeletal defects. Compared with the other 6 children with 2q terminal deletion documented in the literature, this patient is the most severely affected. This patient is also the only one documented to have died and undergone autopsy examination. The findings in this case provide more data for the eventual description of a "terminal 2q deletion syndrome" and suggest that some abnormalities, such as gonadal dysgenesis, may be present in living children with this chromosome abnormality.

Influence of gonadal steroids on rat pituitary growth hormone secretion.

Growth hormone (GH) secretion increases at the time of puberty, and both androgens and estrogens increase the GH response to provocative agents. Little is known, however, with regard to the mechanism or site of action of gonadal steroid-stimulated GH secretion. Using monolayer primary cell culture and radioimmunoassay techniques, insulin-like growth factor I (IGF-I), purified and biosynthetic human GH, 17 beta-estradiol (E2), and testosterone (T) effects on GH release from rat anterior pituitary cells were investigated. Media content of rat GH was measured, both basally and after growth hormone releasing factor (GRF) stimulation. IGF-I at 50 nM concentration inhibited basal rGH release but not in GRF-stimulated cells. E2 (10 pM) stimulated basal secretion of rGH, although higher concentrations did not. High concentrations of T (100,000 pM) caused an increase in GRF-stimulated rGH secretion. Neither purified nor biosynthetic hGH pretreatment influenced subsequent rGH release. These results suggest that IGF-I inhibits and E2 (low dose) and T (high dose) augment rGH release in part at the level of the anterior pituitary.