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D Fowlkes

Publications and source records attributed to D Fowlkes.

5 recordsLinked to original sources

Is laparoscopic donor nephrectomy the new criterion standard?

HYPOTHESIS: The posttransplantation renal function outcomes between consecutive open donor and laparoscopic donor nephrectomies (LDNs) are similar and affect living donation. DESIGN: Using the medical records of renal living donor-recipient pairs, 36 consecutive open donor nephrectomies were compared with the subsequent 100 LDNs. Data collected on donor characteristics included demographics (age, race, sex, weight, and height), renal vascular and ureteral anatomical features, surgical information (blood loss, number of blood transfusions, operating time, warm ischemia time, and renal injury), complications, and length of hospital stay. Recipients' data also included renal function information (serum creatinine level on postoperative days 7 and 30) and ureteral complications during the initial hospital stay. SETTING: A not-for-profit tertiary care teaching hospital in a metropolitan area. PATIENTS: Adults who had end-stage renal disease and received a living donation kidney. MAIN OUTCOME MEASURES: Operative time, warm ischemia time, blood loss, and posttransplantation serum creatinine level. RESULTS: Patient characteristics were not significantly different between the open donor nephrectomy and LDN groups. No right kidney LDNs were done because of the shortness of the right renal vein; and, after the initial experience, left kidneys with more than 2 arteries were excluded. Warm ischemia time was recorded only for LDN, and it was found that a warm ischemia time of 10 minutes or longer was associated with difficulty in extraction and was uniformly associated with elevated mean serum creatinine levels on postoperative day 7. CONCLUSIONS: The length of hospital stay was decreased and cosmetic result enhanced. The number of living donors has increased from 28 in 1997 to 53 in 1998 and to 63 in 1999 at our institution. The length of hospital stay, incidence of complications, and comparable kidney quality indicate that LDN should be the initiating procedure for most patients.

Adolescent↗

Dissection of the LXXLL nuclear receptor-coactivator interaction motif using combinatorial peptide libraries: discovery of peptide antagonists of estrogen receptors alpha and beta.

Recruitment of transcriptional coactivators following ligand activation is a critical step in nuclear receptor-mediated target gene expression. Upon binding an agonist, the receptor undergoes a conformational change which facilitates the formation of a specific coactivator binding pocket within the carboxyl terminus of the receptor. This permits the alpha-helical LXXLL motif within some coactivators to interact with the nuclear receptors. Until recently, the LXXLL motif was thought to function solely as a docking module; however, it now appears that sequences flanking the core motif may play a role in determining receptor selectivity. To address this issue, we used a combinatorial phage display approach to evaluate the role of flanking sequences in influencing these interactions. We sampled more than 10(8) variations of the core LXXLL motif with estradiol-activated estrogen receptor alpha (ERalpha) as a target and found three different classes of peptides. All of these peptides interacted with ERalpha in an agonist-dependent manner and disrupted ERalpha-mediated transcriptional activity when introduced into target cells. Using a series of ERalpha-mutants, we found that these three classes of peptides showed different interaction patterns from each other, suggesting that not all LXXLL motifs are the same and that receptor binding selectivity can be achieved by altering sequences flanking the LXXLL core motif. Most notable in this regard was the discovery of a peptide which, when overexpressed in cells, selectively disrupted ERbeta- but not ERalpha-mediated reporter gene expression. This novel ERbeta-specific antagonist may be useful in identifying and characterizing the ERbeta-regulated process in estradiol-responsive cells. In conclusion, using a combinatorial approach to define cofactor-receptor interactions, we have clearly been able to demonstrate that not all LXXLL motifs are functionally equivalent, a finding which suggests that it may be possible to target receptor-LXXLL interactions to develop receptor-specific antagonists.

Amino Acid Sequence↗

Donor hepatitis C virus status does not adversely affect short-term outcomes in HCV+ recipients in renal transplantation.

BACKGROUND: Recipient hepatitis C virus (HCV) seropositivity has been associated with inferior outcomes in renal transplantation (RTx). We sought to determine whether donor HCV+ status influenced the incidence of rejection, liver dysfunction, and graft survival in HCV+ recipients. METHODS: We reviewed 44 HCV+ recipients (R+) receiving RTx from HCV+ (D+) and HCV- (D-) donors between February 1991 and September 1996. All patients were followed to the end of the study period (mean=36 months, range=12-60 months). We compared the R+ group with a demographically matched cohort of 44 HCV- recipients (R-). RESULTS: Of the 44 R+, 25 (57%) had a total of 48 rejection episodes. Among the 44 R-, 32 (73%) had 58 rejection episodes (P>0.1). Within the R+ group, 28 were D+/R+; of these 14 (50%) had 27 rejection episodes, whereas among the 16 D-/R+, 11 (68%) had 21 rejection episodes (P>0.3). Graft and patient survival was similar in both the groups (86.4% and 91%, respectively). Liver dysfunction was slightly increased in the R+ group (4/44 vs. 0/44, P>0.1), with one death due to liver failure in this group. CONCLUSION: Donor HCV+ status had no influence on outcomes in HCV+ recipients after kidney transplantation in the short term. The incidence of rejection, graft loss, and mortality was comparable between the D+/R+ and D-/R+ groups. Furthermore, rejection, graft loss, and death were identical in R+ and R-groups throughout the 5-year study period. We therefore conclude that HCV+ recipients can safely receive kidney transplants without concern about donor HCV status or fear of adverse events from their own HCV+ status.

Adult↗

Conceptual numerousness judgments by squirrel monkeys.

Two monkeys were reinforced for responding to the card which displayed fewer number of entities (three randomly selected sizes of filled circles) than the other card in any given pair. Area and brightness cues were controlled (at least for the successive numerousness discriminations), as were specific-pattern learning cues. Training proceeded in the order 2 versus 7 (2:7), 2:6, 2:5...2:3, 3:7, 3:6...3:4, etc., until it was judged that the monkeys were unlikely to attain the stringent criteria for discrimination. Both monkeys met criteria on the 7:8 discrimination, and one monkey met criteria on the 8:9 discrimination. It was concluded that the monkeys' numerousness judgments were made on a conceptual basis and that, among nonhuman animals, the evidence for such judgments appears to be limited to apes and monkeys.

Animals↗