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Biomedical subjects

J R Davis

Publications and source records attributed to J R Davis.

At least 37 records · Page 2Linked to original sources
PubMed2000

Wilms' tumor of the cervix: a case report and review of the literature.

INTRODUCTION: Extrarenal Wilms' tumors are rare, with only 55 well-documented cases in the literature and only 4 confined to the uterus. A fifth case along with review of the current literature is presented. CASE: A 13-year-old girl presented with a 2-month history of irregular vaginal spotting. A 6.5 x 4.5 x 2.5-cm polypoid mass meeting criteria for an extrarenal Wilms tumor was removed from the superior aspect of the cervix, but recurred 8 months later on the posterior lip. The patient underwent a Schauta procedure, lymph node dissection, and bilateral oophoropexy. The surgery was followed by typical renal Wilms' tumor chemotherapy. The patient is without evidence of disease 5 years after surgery. DISCUSSION: This case uniquely suggests that limited excision of the original tumor has inherent risks for relapse. Oophoropexy appears to be reasonable when fertility preservation is desired and reconfirms that treatment mimicking renal nephroblastomas offers good long-term survival.

Adolescent↗
PubMed2000

Transcriptional targeting to anterior pituitary lactotrophic cells using recombinant adenovirus vectors in vitro and in vivo in normal and estrogen/sulpiride-induced hyperplastic anterior pituitaries.

The use of pituitary cell type-specific promoters is a powerful molecular tool to achieve pituitary cell type-specific transcriptional targeting of transgenes encoded by viral vectors. It has recently been proposed that transcriptional targeting of therapeutic genes could be harnessed as a gene therapy strategy for the treatment of pituitary disease. We describe the successful use of the human PRL promoter (hPrl) encoded within recombinant adenovirus vectors to target transgene expression of Herpes Simplex Virus Type 1-Thymidine Kinase (HSV1-TK) or beta-galactosidase to lactotrophic cells in vitro and in vivo. Functionally, the restriction of expression of HSV1-TK to lactotrophic tumor cells, using the hPrl promoter, resulted in the cell type-specific induction of apoptosis in the lactotrophic GH3 tumor cell line, in the presence of ganciclovir (GCV). In the corticotrophic AtT20 cell line, we detected neither HSV1-TK expression, nor apoptosis in the presence of GCV. The hPrl promoter encoded within a recombinant adenoviral vector also restricted transgene expression to lactotrophic cells in primary anterior pituitary (AP) cultures, and importantly, within the anterior pituitary gland in vivo. When the HSV1-TK driven by hPrl promoter was used in an in vivo model ofestrogen/sulpiride lactotroph induced hyperplasia within the AP in situ, the treatment was not effective in either reducing the weight of the gland, the number of lactotrophic cells within the transduced area in vivo, or the circulating PRL levels. This is in contrast to the human cytomegalovirus promoter (hCMV) driving expression of HSV1-TK in the same experimental paradigm, which was effective in reducing pituitary weight and circulating PRL levels. Our results have important implications in the design of gene therapy strategies for pituitary tumors. We demonstrate that both the choice of the in vivo animal model, i.e. adenoma in the AP gland in situ, and the particular gene therapy strategy chosen, i.e. use of strong ubiquitous promoters vs. weaker but cell type-specific promoters, determine the experimental therapeutic outcome.

Adenoviridae↗
PubMed2000

Preoperative administration of epoetin alfa to reduce transfusion requirements in elderly patients having primary total hip or knee reconstruction.

Avoidance of allogeneic blood transfusion is challenging in elderly patients with multiple comorbid conditions, who need major elective orthopaedic surgery. We conducted a study comparing the safety and efficacy of preoperative recombinant human erythropoietin (epoetin alfa) in patients having major elective orthopaedic surgery and in matched historical control patients. Patients aged 70 years or more undergoing primary total knee arthroplasty (TKA) or total hip arthroplasty (THA) were given two or three doses, respectively, of epoetin alfa (40,000 IU). They also received oral iron for 14 or 21 days. Epoetin alfa increased hemoglobin (Hb) and hematocrit (HCT) levels before surgery; 74% of control patients required blood transfusion, compared with 12.5% of patients receiving epoetin alfa. No serious adverse event was attributed to study treatment. These data indicate that epoetin alfa is safe and effective and reduces the need for allogeneic blood transfusion in elderly patients having elective total joint replacement.

Aged↗
PubMed1999

Interaction of glucocorticoid receptor isoforms with transcription factors AP-1 and NF-kappaB: lack of effect of glucocorticoid receptor beta.

Glucocorticoids act through the glucocorticoid receptor (GR) to enhance or repress transcription of glucocorticoid responsive genes depending on the promoter context and cellular background. The human GR primary transcript is alternatively spliced resulting in hGR alpha and hGR beta isoforms. Transactivation and transrepression are mediated by hGR alpha and while it has been demonstrated that hGR beta, can act as a dominant negative inhibitor of hGR alpha mediated transactivation, its effects on transrepression are not known. To investigate hGR beta actions, we used GR-deficient COS-7 and HEK-293 cells. When hGR alpha (0.5 microg 10(6) cells(-1)) was transfected into COS-7 cells dexamethasone (150 nM) inhibited TNF alpha (80 U ml(-1)) effects on a NF-kappaB responsive reporter gene by 40%. There was no evidence of a dominant negative effect when hGR beta (1-10 microg) was co-transfected with hGR alpha up to ratios of 10:1. Similarly hGR beta had no effect on hGR alpha inhibition of a phorbol ester stimulated Ap-1-responsive reporter gene in COS-7 or HEK-293 cells. In comparison, an apparent dominant negative effect of hGR beta on hGR alpha-mediated transactivation was found to be attributable to non-specific transcriptional squelching in COS-7 cells. In summary, the potential for hGR beta, to act as a dominant negative inhibitor of hGR alpha-mediated transactivation remains controversial, but our data suggest that hGR beta, was unable to act as a dominant negative inhibitor of either hGR alpha-mediated transrepression or transactivation in these promoter and cell contexts.

Animals↗
PubMed1999

The Bg/II polymorphism of the human prolactin gene lies within intron C and can be detected by PCR/RFLP.

Prolactin has been shown to be active as an immunomodulatory hormone and is therefore of potential importance in disease progression and development. Any polymorphism in the gene and regulatory sequences may prove useful for disease association studies. A Bg/II polymorphism has been previously detected within the prolactin gene region. We have mapped this polymorphism to intron C and detected the base mutation that causes it. We have also developed a PCR-RFLP method to genotype individuals.

Alleles↗
PubMed1999

Recent developments in gene therapy: applications for the treatment of pituitary tumours.

Pituitary tumours are normally benign, highly differentiated and slow growing neoplasms. Nevertheless, as many as half of them will show evidence of local invasion into the surrounding structures. Despite their benign growth characteristics and slow clinical progression, pituitary tumours commonly cause serious morbidity. The mass effects of large tumours, including headache and visual failure from optic chiasm compression, may cause lifelong disability. Hormone hypersecretion or deficiency causes major clinical problems that often require expensive and long-term medical therapy. Major advances have been made in the therapy of pituitary tumours over the past 20-30 years, but despite this, their treatment often remains an unsatisfactory compromise in practice. There is, therefore, a place for improvements in therapy, and to this end, gene therapy may come to hold a significant place in the future treatment of human pituitary tumours. With the development of new gene delivery vehicles, this concept can now be explored with a view to treating specific types of pituitary tumours.

Animals↗
PubMed1999

The human prolactin gene upstream promoter is regulated in lymphoid cells by activators of T-cells and by cAMP.

Prolactin (PRL) is produced in human thymocytes, T-cells and endometrium. In these extrapituitary tissues, PRL gene transcription is directed by an alternative upstream promoter, and it is thought to act as a locally produced cytokine, with relevance for immune regulation and modulation of T-cell function. We have studied PRL transcriptional regulation in the human T-lymphoblastoid Jurkat cell line transfected with a fragment of the upstream promoter linked to luciferase. A cAMP analogue (cptAMP) increased promoter activity rapidly and dose dependently. This increase was resistant to inhibition by cyclosporin A and thus independent of calcineurin phosphatase (CN). T-cell activation by phorbol myristate acetate (PMA) failed to enhance promoter activity but phytohaemagglutinin (PHA) alone or PHA+PMA increased it, and cptAMP acted in synergy with PMA or PHA to increase it further. H-89, a cAMP-dependent protein kinase A (PKA) inhibitor, inhibited the effect of cptAMP as did transfection with protein kinase inhibitor PKI, an expression vector of the specific inhibitor of PKA. A single point mutation in the CRE (cAMP response element) located at -25 bp in the PRL upstream promoter (TGACGT to TGCCGT) failed to reduce the response to cptAMP, while mutations or deletion of four nucleotides in the CRE to TACTCT diminished the response to cAMP by more than half. We conclude that activity of the human PRL upstream extrapituitary promoter can be induced by activators of T-cells, as well as by a cAMP analogue. The signal is transmitted by PKA and the effect of cAMP is independent of CN. It is partly dependent on an intact proximal CRE motif but a more upstream enhancer may contribute to promoter regulation.

Base Sequence↗
PubMed1999

Influence of body condition score on carcass characteristics and subprimal yield from cull beef cows.

Mature beef cows (n = 83) were slaughtered to measure the influence of body condition score (BCS) on carcass characteristics and subprimal yields. All cows were weighed and assigned BCS, based on a 9-point scale, 24 h before slaughter. Cows were slaughtered, and, after a 48-h chilling period, quality and yield grade data were collected on the left side of each carcass. The right side was quartered, fabricated into primal cuts, and weighed. Each primal cut was further processed into boneless subprimal cuts, minor cuts, lean trim, fat, and bone. Cuts were progressively trimmed to 6.4 and 0 mm of external and visible seam fat. Weights were recorded at all stages of fabrication, and subprimal yields were calculated as a percentage of the chilled carcass weight. Live weight, carcass weight, dressing percentage, fat thickness, longissimus muscle area, muscle:bone ratio, and numerical yield grade increased linearly (P = .0001) and predicted cutability and actual muscle-to-fat ratio decreased linearly (P = .0001) as BCS increased from 2 to 8. Carcasses from BCS-8 cows had the most (P<.05) marbling. The percentage of carcasses grading U.S. Utility, or higher, was 16.7, 20.0, 63.6, 43.3, 73.3, 100.0, and 100.0% for cows assigned a BCS of 2, 3, 4, 5, 6, 7, and 8, respectively. At 6.4 mm of fat trim, carcasses from BCS-5 cows had higher (P<.05) shoulder clod yields than carcasses from cows having a BCS of 6, 7, and 8. Carcasses of BCS-2 cows had lower (P<.05) strip loin yields than carcasses from BCS-3, 4, 5, 6, and 7 cows. Top sirloin butt yields were higher (P<.05) for carcasses of BCS-2, 3, 4, and 5 cows than those of BCS-6, 7, or 8 cows. Carcasses from BCS-7 and 8 cows had lower (P<.05) tenderloin and inside round yields than carcasses of BCS-5, or less, cows. At both fat-trim levels, carcasses from BCS-5 cows had higher (P<.05) eye of round yields than cows assigned BCS of 2, 7, or 8. When subprimal cuts were trimmed to 6.4 mm of visible fat, carcasses from BCS-5 cows had higher (P<.05) total lean product yields than cows assigned a BCS of 2, 4, 7, and 8. Regardless of fat trim, total fat yields increased (P = .0001) and total bone yields decreased (P = .0001) linearly as BCS increased from 2 to 8. Although carcasses from BCS-5 and 6 cows had the highest yields of lean product, cattle producers and packers may benefit most by marketing and(or) purchasing BCS-6 cows because a higher percentage of their carcasses had quality characteristics deemed desirable for fabrication into boneless subprimal cuts.

Animal Husbandry↗
PubMed1999

Ultrasound: impact on diagnostic peritoneal lavage, abdominal computed tomography, and resident training.

Our objective was to determine the impact of abdominal ultrasound (US) on 1) the use of diagnostic peritoneal lavage (DPL) and abdominal computed tomography (ACT) for diagnosing blunt abdominal trauma (BAT) and on 2) surgical resident training. The study design was a retrospective chart review. Patients sustaining BAT who had ACT or DPL done during the 1-year period before the introduction of US (pre-US) were compared with those from a 1-year period beginning 6 months after US (post-US). Data collected included diagnostic modality, demographic data, mortality, associated injuries, length of stay, mechanism of injury, and number of exploratory laparotomies. Of 128 patients in the pre-US group, 35 patients (27%; P < 0.001) underwent DPL, 0 patients (0%; P < 0.001) received US, and 92 patients (72%) received ACT, with positive results for 31 patients (34%). Exploratory laparotomy was performed on 35 patients (27%) in the pre-US group. Of 140 patients in the post-US group, 8 patients (6%; P < 0.001) underwent DPL, 120 patients (85%; P < 0.001) received US, and 108 patients (77%) received ACT, with positive results for 44 patients (42%). Exploratory laparotomy was performed on 22 patients (15%; P < 0.001) in the post-US group. Resident experience with DPL before and after the introduction of US and availability of US for graduated residents was documented. Chi-square and Fisher's exact test were used for statistical analysis. Resident experience changed from 22 to 3 DPLs per year in the pre- and post-US groups, respectively. Ten per cent of graduating residents had US available for use after leaving this institution. US replaced DPL and resulted in slightly more positive ACT scans in assessing BAT at our institution. Paradoxically, only 10 per cent of graduating residents had US available after leaving this institution. Until the use of US for diagnosing BAT has widespread use in the community, we must question our adequacy of resident preparation for diagnosing BAT.

Abdomen↗
PubMed1999

Chromosome abnormalities in ovarian adenocarcinoma: I. Nonrandom chromosome abnormalities from 244 cases.

Cytogenetics provides important insights into the molecular pathogenesis of human cancers. Although extensive data exist on recurring cytogenetic abnormalities in hematologic cancers, data on individual solid tumor types remain limited. Previous studies of ovarian carcinoma indicated the presence of multiple, complex clonal chromosome abnormalities. Cytogenetics remains one of a few techniques capable of detecting these multiple, simultaneously occurring genetic abnormalities. We describe cytogenetic abnormalities from a series of 244 primary ovarian cancer specimens referred to a single institution. A total of 201/244 cases had fully characterized clonal chromosome abnormalities, of which 134 showed clonal chromosome breakpoints. We used a novel statistical technique to detect nonrandom chromosome breakpoints at the level of chromosome regions. Nonrandom occurrence of chromosome breakpoints was detected at regions 1p1*, 1q1*, 1p2*, 1q2*, 1p3*, 1q3, 3p1*, 1q4*, 6q1*, 6p2, 6q2, 7p1*, 7q1, 7p2*, 11p1*, 11q1, 11q2*, 12p1, 12q2*, 13p1, and 19q1. Simultaneous occurrence of multiple abnormalities was common. However, 120/134 cases had breakpoints at one or more of 13 commonly involved regions (*), suggesting a hierarchy of genetic abnormalities. Among clinical and tumor variables that predict patient survival, tumor grade was significantly associated with the presence of chromosome breakpoints. In additional studies, we show that nonrandom chromosome abnormalities are associated with impaired survival in ovarian cancer and that specific, nonrandomly involved chromosome regions retain significant effects on survival when analyses are controlled for important clinical variables. Additional specific chromosome abnormalities in this series are described, including chromosome gains and losses in near-diploid cases and homogeneously staining regions. These results suggest that recurring, nonrandom chromosome abnormalities are important in the pathogenesis and/or progression of ovarian cancers, and target areas of the genome for molecular genetic studies.

Adenocarcinoma↗
PubMed1998

Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene.

X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.

Antigens, CD↗