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Biomedical subjects

T Hurd

Publications and source records attributed to T Hurd.

7 recordsLinked to original sources

Computational identification of human mitochondrial proteins based on homology to yeast mitochondrially targeted proteins.

MOTIVATION: Patients with defects of the mitochondrial respiratory chain due to mutations in nuclear genes are often undiagnosable due to the lack of information about the role of these genes. We therefore sought to produce a novel dataset of human nuclear-encoded mitochondrial proteins. RESULTS: We have used the web-based computer program Mitoprot to predict which proteins in the Saccharomyces cerevisiae genome are targeted to mitochondria. We then used this protein dataset to identify the homologous human proteins in the Unigene database using TBLASTN from NCBI. Human proteins with an Expectation value <10(-5) and an Identity >30% were accepted as true homologues of the yeast proteins. These human proteins were then reanalyzed with Mitoprot. The final set of proteins comprises a dataset of 361 human mitochondrially targeted proteins with homology to all S.cerevisiae mitochondrially targeted proteins. One hundred twenty eight of these proteins are novel and are of unknown function. SUPPLEMENTARY INFORMATION: Supplementary tables will be available from http://www.sickkids.ca/Robinsonlab/

Conserved Sequence↗

Is MUGA scan necessary in patients with low-risk breast cancer before doxorubicin-based adjuvant therapy? Multiple gated acquisition.

Doxorubicin-based chemotherapy in the adjuvant treatment of breast cancer has become standard. Use of doxorubicin is limited by cardiac dysfunction; however, the incidence is dramatically reduced by limiting the dose to less than 550 mg/m(2). Although the cumulative dose in breast cancer is typically 240 mg/m(2), multiple gated acquisition (MUGA) scans are still recommended for determining cardiac functional status in these patients. To examine the need for this practice, we reviewed 296 patients who underwent surgery for breast cancer at Roswell Park Cancer Institute between July 1997 and December 1998. Fifty-nine of 95 (62%) patients receiving doxorubicin-based regimens, and 3 of 39 (7%) receiving nondoxorubicin regimens had pretreatment MUGA scans. The MUGA scans showed normal results in 58 patients and low-normal in 4 (6.5%), with no wall motion abnormalities encountered. There were no cases where doxorubicin was not used because of an abnormal MUGA scan. There were no cardiac complications in the 59 women who received doxorubicin-based chemotherapy. MUGA will screen out few, if any, women under consideration for doxorubicin-based adjuvant therapy; the decision to avoid doxorubicin can be made based on age and preexisting comorbidity. Guidelines recommending routine use of MUGA before the administration of doxorubicin for adjuvant therapy for breast cancer should be reconsidered.

Adult↗

Temporal relationship of hepatocellular dysfunction and ischemia in sepsis.

To determine whether hepatic dysfunction in sepsis results from hypoperfusion or direct cellular injury, Sprague-Dawley rats underwent either cecal ligation and puncture or sham operation. After either two or six hours, effective hepatic blood flow was measured using the galactose clearance method. Hepatocytes were isolated and intracellular sodium and potassium and glucose production were measured. Hepatic blood flow in septic rats decreased as early as two hours after sepsis when compared with sham-operated rats (3.8 +/- 1.4 vs 8.7 +/- 3.1 mL/min/100 g body weight). Intracellular sodium and potassium levels and glucose production in septic rats were not significantly different when compared with controls at two hours. After six hours, hepatic blood flow remained depressed and intracellular sodium level was increased compared with sham-operated rats (41.7 +/- 10.4 vs 31.4 +/- 5.9 mmol/L [41.7 +/- 10.4 vs 31.4 +/- 5.9 mEq/L]) and potassium decreased compared with controls (90.7 +/- 7.9 vs 111.5 +/- 6.7 mmol/L [90.7 +/- 7.9 vs 111.5 +/- 6.7 mEq/L]). Glucose production was decreased in septic rats after six hours when compared with controls (4.7 +/- 1.5 vs 15.4 +/- 6.4 mumol/g hepatocytes). These data suggest that hepatic blood flow is decreased before alterations in intracellular sodium and potassium as well as glucose production.

Animals↗

Intra-abdominal infection following combined spleen-colon trauma.

The reality of late overwhelming post-splenectomy sepsis in adults as well as children has led to more frequent attempts at splenic salvage following splenic trauma. Less attention has been paid to early septic postoperative complications in the splenectomized patient. Associated colon injury has been believed to be a relative contraindication to splenic conservation. If splenectomy enhances the chance of early postoperative infection, then associated colon injury should be an indication for splenic salvage One hundred sixty one patients who had either splenic trauma (58), colon trauma (90), or combined spleen-colon trauma (13) were studied. All patients with splenic trauma had a splenectomy. There was a significantly higher incidence of intra-abdominal sepsis requiring reoperation in the spleen-colon patients (46.7%) than in either of the other groups (spleen = 5.7%, colon = 8.9%, P less than .002 for both comparisons). It is concluded that splenectomy enhances infection in the early postoperative period. When possible, combined spleen-colon trauma should be an indication rather than a contraindication for splenic salvage.

Abdomen↗