Characterisation of glucuronidation and transport in V79 cells co-expressing UGT1A1 and MRP1.

The co-ordinated glucuronidation and export of compounds from cells is an important determinant in the detoxification of many compounds in vivo. Many UDP-glucuronosyltransferases (UGTs) and several multidrug resistance proteins (MRPs) have been cloned and individually expressed to assess specificity of glucuronidation and transport. However, to further understand the interplay between glucuronidation and transport we are developing stable cell lines that express different combinations of UGT and MRP isoforms. V79 cells expressing both UGT1A1 and MRP1 have been established. The ability of these cell lines to both glucuronidate and transport compounds was assessed ex vivo using estradiol and bilirubin as substrates.

Nonoperative management of blunt liver trauma: the value of follow-up abdominal computed tomography scans.

Our hypothesis was that follow-up abdominal CT scans are not routinely necessary in patients with blunt liver injury treated nonoperatively. We conducted an 8-year retrospective review of hospital chart and outpatient clinic records. We reviewed all admission and follow-up CT scans. There were 42 adults and 12 children. There were 1 (2%) grade I, 15 (28%) grade II, 28 (52%) grade III, 8 (15%) grade IV, and 2 (4%) grade V liver injuries. Two patients died during the first 24 hours, both from associated injuries. Nonoperative management was successful in 51 (98%) of the remaining 52 patients. No follow-up abdominal CT scans were performed on 21 (40%) patients; none developed hepatic complications. An initial follow-up CT scan was obtained in 31 (60%) patients. Information from these scans directly affected management in 3 (9%) patients; in each case, the scans were prompted by a change in clinical status. One significant biloma with bile leak was managed by nasobiliary stenting and percutaneous drainage. One hepatic artery-to-portal vein fistula was obliterated by transarterial embolization. A single missed diaphragm rupture necessitated laparotomy. Additional late follow-up CT scans were obtained in 13 patients; no clinically useful information was evident on any of these examinations. We conclude that follow-up abdominal CT scans are not routinely necessary in patients with liver injuries treated nonoperatively. Selective criteria based on the severity of liver injury, presence of associated intra-abdominal pathology, and clinical parameters should dictate the need for follow-up imaging studies.

Immunochemical detection of arylamine N-acetyltransferase in normal and neoplastic bladder.

The N-acetyltransferase (NAT) phenotype is an important determinant of individual susceptibility to occupational bladder cancer. N-Acetyltransferases arc known to metabolize aromatic amine bladder carcinogens, but the functional significance of NAT expression in the target organ is unclear. To resolve this issue, polygonal antisera against purified recombinant enzymes and C-terminal peptides of human NAT Type 1 (NAT1) and Type 2 (NAT2) were generated. Western blot analysis of exfoliated cells from human urine, pig bladder homogenate, and human bladder tumor-derived cell lines showed that NAT1 was expressed in all three systems, whereas NAT2 did not appear to be expressed in the bladder. Immunohistochemical analysis of human bladder tumor sections indicated that well-differentiated tumor cells expressed NAT1, with the highest level of expression being found in the umbrella cells that line the bladder lumen. Poorly differentiated tumor regions appeared to express NAT1 at lower levels than did well-differentiated areas. These findings support the hypothesis that aromatic amines are metabolized in the bladder epithelium by NAT1.

How biomedical investigators use library books.

Relatively few studies have been concerned with the use of biomedical books. This paper reports an investigation into use made of library books by biomedical investigators. Based on cancelled charge slips collected at the Yale Medical Library circulation desk, telephone appointments were made to interview those research investigators whose books had been returned the previous day. The interviewer obtained answers from the investigator to a questionnaire to discover how the investigator had learned of a book, if the book had been useful, and, if useful, how it had been used. During the six-month study period, 30.4 percent of researchers' volumes returned were monographs. Almost four-fifths of books borrowed supplied information wanted, and about four-fifths of books used had been printed in the previous decade. Nine-tenths of the use of books was research-related, the other tenth being for lecture preparation.