PubMed Health⌕ Search

Biomedical subjects

A Whalen

Publications and source records attributed to A Whalen.

7 recordsLinked to original sources
PubMed1997

Phosphorylation within the transactivation domain of adenovirus E1A protein by mitogen-activated protein kinase regulates expression of early region 4.

A critical role of the 289-residue (289R) E1A protein of human adenovirus type 5 during productive infection is to transactivate expression of all early viral transcription. Sequences within and proximal to conserved region 3 (CR3) promote expression of these viral genes through interactions with a variety of transcription factors requiring the zinc binding motif in CR3 and in some cases a region at the carboxy-terminal end of CR3, including residues 183 to 188. It is known that 3',5' cyclic AMP (cAMP) reduces the level of phosphorylation of the 289R E1A protein through the activation of protein phosphatase 2A by the E4orf4 protein. This study was designed to identify the E1A phosphorylation sites affected by E4orf4 expression and to determine their importance in regulation of E1A activity. We report here that two previously unidentified sites at Ser-185 and Ser-188 are the targets for decreased phosphorylation in response to cAMP. At least one of these sites, presumably Ser-185, is phosphorylated in vitro by purified mitogen-activated protein kinase (MAPK), and both are hyperphosphorylated in cells which express a constitutively active form of MAPK kinase. Analysis of E1A-mediated transactivation activity indicated that elevated phosphorylation at these sites increased expression of the E4 promoter but not that of E3. We have recently shown that one or more E4 products induce cell death due to p53-independent apoptosis, and thus it seems likely that one role of the E4orf4 protein is to limit production of toxic E4 products by limiting expression of the E4 promoter.

Adenovirus E1A Proteins↗
PubMed1996

The bona fide mouse U7 snRNA gene maps to a different chromosome than two U7 pseudogenes.

The U7 snRNA, together with both common and unique snRNP proteins, forms the U7 snRNP particle. This particle is a major component of the 3' processing machinery that converts histone pre-mRNA into mature mRNA in the eukaryotic nucleus. The genes for many snRNAs are present in multiple copies and often have many pseudogenes. Southern blot experiments using U7 oligonucleotide and gene probes have identified only one strongly hybridizing band and three weakly hybridizing bands in mouse genomic DNA. Previously, two laboratories isolated genomic clones encoding one functional U7 gene and three presumed pseudogenes. Since all the genes were isolated on separate, nonoverlapping genomic fragments, the four genes are not tightly clustered in the mouse genome. In this study, we use fluorescence in situ hybridization to determine the chromosomal locations of these clones and their possible linkage to histone loci. Two of the pseudogenes map to mouse Chromosome 1, but are many megabases apart, whereas the active U7 gene maps to Chromosome 6. Possible mechanisms for this localization pattern are discussed.

Animals↗
PubMed1994

Home antibiotic therapy for low-risk cancer patients with fever and neutropenia: a pilot study of 30 patients based on a validated prediction rule.

PURPOSE: To assess the feasibility of early discharge to home therapy with standard intravenous antibiotics in 30 patients with fever and neutropenia at low risk by a validated clinical decision rule. PATIENTS AND METHODS: Newly admitted outpatients with fever and neutropenia were evaluated for home therapy during 2 days of inpatient observation. To evaluate enrolled patients' acceptance of home care, we assessed patient attitudes and quality of life before and after home therapy. To assess economic effects, we compared the medical charges of patients treated at home with those of medically eligible patients who remained in the hospital. RESULTS: Of the first 84 patients, 50 (60%) were medically ineligible, and neutropenia was resolved in another eight (10%) during the observation period. Only nine patients of the remaining 26 who were medically eligible (35%) were enrolled in the home-therapy trial. Thereafter, 21 of 31 medically eligible patients (68%) were enrolled. The 30 patients treated at home were neutropenic for a median of 6 days (mean, 8.2). Four had medical complications, and five others were readmitted for observation. Patients' quality of life improved during home therapy, and favorable attitudes toward home care persisted after treatment. Medically eligible patients not enrolled had briefer neutropenia than patients treated at home, but had 44% higher daily medical charges and equivalent overall charges despite treatment half as long. CONCLUSION: We conclude that early discharge of low-risk patients to home intravenous antibiotic therapy is feasible, is well received by patients, and may prove to be cost-saving. However, these conclusions must be validated in a large randomized trial.

Adolescent↗
PubMed1993

Reduction by combination prophylactic therapy with CMV hyperimmune globulin and acyclovir of the risk of primary CMV disease in renal transplant recipients.

CMV-seronegative recipients of kidneys from CMV-seropositive donors (D+/R+) are at highest risk for developing clinical CMV disease. Even with routine prophylactic use of low-dose acyclovir we had a CMV disease incidence of 26% (5/19) in these patients. Published studies using either acyclovir or CMV hyperimmune globulin (HIG) alone as prophylaxis have also shown clinical disease in 20-30% of D+/R+ patients--less than controls but still significantly greater than in comparable CMV+ recipients (R+). The purpose of this study was to determine whether the risk of primary CMV disease in D+/R- patients was reduced by prophylaxis with combined CMV-HIG and low-dose acyclovir as follows: CMV-HIG (Immuno) 1 ml/kg i.v. immediately prior to transplantation and at 3-week intervals for 6 months; acyclovir 600 mg/day p.o. for 3 months. A total of 361 consecutive renal transplants were studied prospectively. All D+/R- pts (n = 73) received CMV-HIG and acyclovir, the others (91 D+/R+, 74 D-/R+, 123 D-/R-) received only low-dose acyclovir. The incidence of clinical CMV disease, CMV-related graft loss, graft and patient survival, and the influence of ALG and OKT-3 were analyzed and compared between groups. Of the 361 patients only 18 (5%) developed CMV disease, with 5 CMV-related graft losses. CMV disease occurred in only 10% of the D+/R- patients, lower than in previously reported studies. Significantly the incidence was as low as in CMV+ recipients of kidneys from both CMV+ (6%) and CMV- (7%) donors. Use of OKT-3 for steroid-resistant rejection increased the risk of developing CMV disease: 11/50 (22%) receiving OKT-3 developed CMV disease vs. only 7/311 (2%) who did not (P < 0.001); 11/18 (61%) with CMV disease had received OKT-3. ALG induction immunosuppression did not increase the risk of CMV in patients who subsequently received OKT-3. No patient developed CMV disease after discontinuing prophylaxis. There were no complications related to either CMV-HIG or acyclovir use. Compared with all other patients, the D+/R- group had superior graft survival at 1 and 3 years (94% vs. 87% and 86% vs. 74%, P < 0.05) but similar patient survival. Combined CMV-HIG and low-dose acyclovir appear to be better than either agent alone in preventing primary CMV disease in CMV- patients who receive CMV+ kidneys. Low-dose oral acyclovir (600 mg/day) may be as effective in preventing CMV disease as higher-dose prophylactic regimens, at least when accompanied by CMV-HIG.(ABSTRACT TRUNCATED AT 400 WORDS)

Acyclovir↗