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Biomedical subjects

David Griffin

Publications and source records attributed to David Griffin.

16 recordsLinked to original sources
PubMed2006

N-sulfonyloxy carbamates as reoxidants for the tethered aminohydroxylation reaction.

The use of N-sulfonyloxy carbamates as reoxidants for the tethered aminohydroxylation (TA) reaction is reported. These new conditions obviate the requirement for lithium hydroxide and tBuOCl in the oxidation mixture. In addition to providing aminohydroxylation products in good yields, the catalyst loadings can be reduced to just 1 mol % osmium. Moreover, for the first time, homoallylic alcohols are now viable substrates for the TA reaction.

Carbamates↗
PubMed2005

Ovarian cancer complicated by invasive pulmonary aspergillus.

BACKGROUND: Invasive aspergillus is a rarely reported infection in patients with solid tumors. CASE: A 59-year-old woman developed invasive pulmonary aspergillus after surgical debulking of an advanced ovarian adenocarcinoma and initiation of adjuvant combination chemotherapy. CONCLUSION: Invasive pulmonary aspergillus is rarely diagnosed in patients with solid tumors such as ovarian cancer. Risk factors for development of the disease can include neutropenia, immunosuppression and chronic steroid use. Successful treatment of the infection relies upon prompt diagnosis and utilization of effective antifungal medications for a prolonged period of time.

Aspergillosis↗
PubMed2005

The simultaneous modelling of metal ion and humic substance transport in column experiments.

Pulsed column experiments using Co, fulvic acid and porous sediment packing, along with up/down-flooding experiments using Eu, humic acid and intact sandstone blocks have been performed. The elution of metal and humic and their distribution along the sandstone columns have been measured. A mixed equilibrium and kinetic coupled chemical transport model has been used to simulate the results. In both cases, one exchangeable and one non-exchangeable component have been used to simulate the interaction of metal and humic substance. For the pulsed experiments, a simple equilibrium approach was used to model humic sorption, while a two component, kinetic model was required for the sandstone columns.

Adsorption↗
PubMed2005

Cornelia de Lange Syndrome in association with a balanced reciprocal translocation involving chromosomes 3 and 5.

We present a case report on a fetus with multiple malformations, diagnosed by ultrasound at 20 weeks' gestation. From the combination of intrauterine growth retardation and limb abnormalities that were observed, the most likely diagnosis was considered to be Cornelia de Lange Syndrome (CdLS). Following counselling, the mother opted to terminate the pregnancy. Chromosome analysis of cultured amniotic fluid cells showed a karyotype of 46,XX,t(3;5)(q21;p13). Postmortem examination of the baby confirmed the presence of features consistent with a diagnosis of CdLS. This case provides a report of a definitive diagnosis of Cornelia de Lange Syndrome, suspected on the basis of ultrasound imaging and confirmed by amniocentesis findings.

Abortion, Induced↗
PubMed2005

Sites of bowel resected to achieve optimal ovarian cancer cytoreduction: implications regarding surgical management.

OBJECTIVE: The purpose of this study was to 1) report on the distribution of bowel segments resected in a population of patients who underwent primary optimal cytoreductive surgery for epithelial ovarian cancer, and 2) discuss implications for surgical management regarding resection of these bowel segments. STUDY DESIGN: This was a retrospective study from 1995 to 2003 of 144 ovarian cancer patients who underwent primary optimal cytoreductive operations that included bowel resection. RESULTS: Bowel segments removed and major complications are presented in tabulated form. Eighty-one out of 144 resections were rectosigmoid only. Thirty-six percent had extensive involvement of colon segments separate from the rectosigmoid. Excluding hemorrhage, 9 patients (6%) experienced a major complication. CONCLUSION: The present study does suggest the necessity for a highly individualized approach to the surgical management of epithelial ovarian cancer patients who can be optimally cyto-reduced by resection of multifocal colonic involvement. Further study is needed to better assess the complications, function, and oncologic outcome of the different surgical approaches to these patients.

Adult↗
PubMed2005

Adenocarcinoma in situ of the cervix in pregnancy.

INTRODUCTION: The number of patients diagnosed with adenocarcinoma in situ of the cervix has increased in the last decade. The number of pregnant patients with this disease can also be expected to increase. CASES: In this report, we describe three patients diagnosed with adenocarcinoma in situ of the cervix during pregnancy. DISCUSSION: The management of adenocarcinoma in situ of the cervix may include procedures which present substantial risks to an ongoing pregnancy and more conservative management may be warranted in many instances.

Adenocarcinoma↗
PubMed2005

Canine plasma and erythrocyte response to a docosahexaenoic acid-enriched supplement: characterization and potential benefits.

Results of this study confirm that dietary supplementation in dogs with a natural source of omega-3 fatty acids (salmon oil), with a docosahexaenoic acid:eicosapentaenoic acid (DHA:EPA) ratio of 1.5:1, increases plasma and red blood cell levels of these fatty acids. Supplementation with this DHA-enriched oil improves the long-chain polyunsaturated fatty acid omega-6:omega-3 (n-6:n-3) ratio, which may benefit dogs of all ages. Studies describing some of the neurologic, renal, cardiovascular, immune, and musculoskeletal effects of elevated blood levels of n-3 fatty acids, especially DHA, are reviewed. The importance of providing an enriched source of DHA, instead of its shorter precursors, is emphasized.

Animals↗
PubMed2004

Accuracy of pelvic examination in the assessment of patients with operable cervical cancer.

OBJECTIVE: The purpose of this study was to determine whether pelvic examination identifies factors that suggest the need for radiotherapy after radical hysterectomy for cervical cancer. STUDY DESIGN: This was an observational study that was conducted from July 1, 2000 through December 31, 2002 that comprised 67 patients with stage 1B-2A cervical cancer who underwent primary surgical treatment. Assessments that were made on pelvic examination were compared with pathologic findings. Data were analyzed with the use of descriptive statistics, calculation of sensitivities, specificities, positive and negative predictive values, and determination of odds ratios. RESULTS: The overall spectrum of small to large tumors (<1-8 cm) and cervices (2.5-8 cm) correlated well with examination (r=0.77-0.88). The accuracy of examination was approximately 50% for tumor diameter (+/-25%), 85% for cervical diameter (+/-25%), 80% for outer-third invasion, 80% for endophytic growth, and 90% for vaginal involvement. The likelihood for adjuvant radiotherapy had a significant association with the number of at-risk examination variables that were present. CONCLUSION: For women who undergo radical hysterectomy for stage 1B to 2A cervical cancer, the presence of multiple high-risk factors that are found on pelvic examination is associated significantly with indications for adjuvant postoperative radiotherapy.

Adenocarcinoma↗
PubMed2004

Superior vena cava syndrome during chemotherapy for stage 3c fallopian tube adenocarcinoma.

BACKGROUND: Superior vena cava syndrome is most often encountered in patients with malignancies. The diagnosis constitutes an oncologic emergency with prompt treatment indicated to manage the acute symptoms. There are few reports describing the syndrome in patients with gynecologic malignancies and central venous catheters. Management has included treatment of the metastatic disease and anticoagulation/thrombolysis with catheter removal early in therapy. CASE REPORT: The case described is the first report of a patient with fallopian tube carcinoma complicated by SVC syndrome. The complication was attributed to an implanted venous access port being utilized to give adjuvant combination chemotherapy. CONCLUSIONS: Superior vena cava syndrome is rarely encountered in gynecologic oncology patients and constitutes a medical emergency. When encountered in the setting of an implanted catheter, thrombolysis and anticoagulation is an alternative to catheter removal in selected patients.

Adenocarcinoma↗
PubMed2004

Lysophospholipids are potential biomarkers of ovarian cancer.

OBJECTIVE: To determine whether lysophosphatidic acid (LPA) and other lysophospholipids (LPL) are useful markers for diagnosis and/or prognosis of ovarian cancer in a controlled setting. METHOD: Plasma samples were collected from ovarian cancer patients and healthy control women in Hillsborough and Pinellas counties, Florida, and processed at the University of South Florida H. Lee Moffitt Cancer Center and Research Institute (Moffitt). Case patients with epithelial ovarian cancer (n = 117) and healthy control subjects (n = 27) participated in the study. Blinded LPL analysis, including 23 individual LPL species, was performed at the Cleveland Clinic Foundation using an electrospray ionization mass spectrometry-based method. LPL levels were transmitted to Moffitt, where clinical data were reviewed and statistical analyses were performed. RESULTS: There were statistically significant differences between preoperative case samples (n = 45) and control samples (n = 27) in the mean levels of total LPA, total lysophosphatidylinositol (LPI), sphingosine-1-phosphate (S1P), and individual LPA species as well as the combination of several LPL species. The combination of 16:0-LPA and 20:4-LPA yielded the best discrimination between preoperative case samples and control samples, with 93.1% correct classification, 91.1% sensitivity, and 96.3% specificity. In 22 cases with both preoperative and postoperative samples, the postoperative levels of several LPL, including S1P, total LPA, and lysophosphatidylcholine (LPC) levels and some individual species of LPA and LPC, were significantly different from preoperative levels. CONCLUSION: LPA, LPI, LPC, and S1P appear useful as diagnostic and prognostic biomarkers of ovarian cancer.

Adolescent↗
PubMed2003

Isolation of the B3 transcription factor of the Xenopus TFIIIA gene.

The selective expression of the Xenopus TFIIIA gene in immature oocytes is principally regulated by a single 5'-flanking DNA sequence element, termed element 3 (i.e. E3). We describe the isolation and characterization of a cDNA for a protein present in immature Xenopus ooctyes, termed B3.65, which appears to bind to and activate E3-mediated expression. The approximate molecular weight of the E3 binding protein(s) was determined by ultraviolet light cross-linking analysis. B3.65, a protein of the appropriate molecular weight, was purified biochemically from immature Xenopus ooctye extracts by affinity chromatography. Antiserum to purified B3.65 super-shifted the E3 activator complex. In addition, B3.65 mRNA was found to be highly enriched in immature oocytes. All of these data are consistent with B3.65 either being the E3 activator, or antigenically related to the specific activator required for XenopusTFIIIA gene transcription. B3.65 is a member of the K-homologous (KH) domain family of proteins, with almost absolute identity to Xenopus Vg1 RBP/VERA (97%) and significant similarity to human koc (82%). The koc mRNA is over-expressed in human pancreatic cancer tissues, and B3.65 mRNA was detected in Xenopus pancreas and kidney. Interestingly, KH proteins, like Vg1RBP/VERA, are most commonly associated with RNA metabolism, in their capacity to regulate RNA localization, stability, and translation. Our results suggest that B3.65 is a key regulator of both RNA- and DNA metabolism.

Amino Acid Sequence↗
PubMed2003

The Xenopus B2 factor involved in TFIIIA gene regulation is closely related to Sp1 and interacts in a complex with USF.

In the Xenopus laevis oocyte there is a million fold more transcription factor IIIA (TFIIIA) and its corresponding mRNA than in a somatic cell. These high levels of TFIIIA gene expression are achieved primarily by transcriptional regulation. The TATA box along with three positive cis-elements in the control region of the TFIIIA gene located at positions -269 to -264 (E1), -235 to -220 (E2), and -669 to -636 (E3) are required for this high level of expression in oocytes. The proteins that bind E1 and E3 of the TFIIIA gene have been identified as Xenopus USF (Xl-USF) and B3 (homolog of Vg1 RBP/VERA). In this study the B2 protein was found to bind E2 in a zinc-dependent fashion and anti-human Sp1 (but not Sp2, Sp3, nor Sp4) supershifted the B2:element 2 complex. The E2 binding protein was purified by DNA affinity chromatography. Based on supershift analysis, molecular weight estimation experiments, and purified human Sp1 DNA binding affinity tests the data strongly support the idea that the B2 protein is the Xenopus ortholog of Sp1, but not Sp2, Sp3, nor Sp4. Xl-USF binds to element 1 of the TFIIIA gene which is immediately adjacent to element 2. Coimmunoprecipitation experiments using crude whole oocyte extracts revealed that Xenopus Sp1 and USF or closely related factors are present together in a high-affinity complex. This structure contributes positively to the initiation of TFIIIA gene transcription in Xenopus oocytes.

Animals↗
PubMed2003

Molecular determinants of epothilone B derivative (BMS 247550) and Apo-2L/TRAIL-induced apoptosis of human ovarian cancer cells.

OBJECTIVE: We determined the cytotoxic effects BMS 247550 (Epo B), a derivative of epothilone B, on cisplatinum- or paclitaxel-sensitive or -resistant human ovarian cancer cells. Additionally, we determined the effect of Epo B on Apo-2L/TRAIL-induced apoptosis of ovarian cancer cells. METHODS: Epo B-induced cytotoxic and cell cycle effects were evaluated by the MTT assay and flow cytometry, respectively. Epo B-induced apoptosis was assessed by immunoblot analyses of the processing and proteolytic activity of caspases, flow cytometric measurement of annexin V staining, and the TUNEL assay. The effects of Epo B and/or Apo-2L/TRAIL on the protein expressions of the death receptors DR4 and DR5 as well as of XIAP and survivin were determined by immunoblot analyses. RESULTS: In the cell cycle-synchronized ovarian cancer cells, Epo B induced tubulin polymerization and mitotic arrest, followed by apoptosis. This was associated with the cytosolic accumulation of cytochrome (cyt) c and Smac/DIABLO as well as PARP cleavage activity of caspase-3. Epo B was able to exert cytotoxic effects against cisplatinum- and paclitaxel-resistant ovarian cancer cells. Epo B increased the expressions of DR4 and DR5, as well as augmented Apo-2L/TRAIL-induced processing of caspase-8 and Bid. This was associated with more caspase-3 activity, a decline in the intracellular levels of XIAP, cIAP, and survivin, and apoptosis of ovarian cancer cells. CONCLUSIONS: These data support the in vivo testing of Epo B against cisplatinum- and paclitaxel-resistant ovarian cancers, and suggest that a pretreatment with Epo B may sensitize human ovarian cancers to the cytotoxic effects of Apo-2L/TRAIL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Ectopic overexpression of second mitochondria-derived activator of caspases (Smac/DIABLO) or cotreatment with N-terminus of Smac/DIABLO peptide potentiates epothilone B derivative-(BMS 247550) and Apo-2L/TRAIL-induced apoptosis.

Second mitochondria-derived activator of caspases (Smac)/DIABLO is a mitochondrial protein that is released into the cytosol along with cytochrome c (cyt c) during the execution of the intrinsic pathway of apoptosis. Smac/DIABLO promotes apoptosis by neutralizing the inhibitory effect of the inhibitor of apoptosis (IAP) family of proteins on the processing and activities of the effector caspases. Present studies demonstrate that, upon engagement of the mitochondrial pathway of apoptosis, epothilone (Epo) B derivative BMS 247550, a novel nontaxane antimicrotubule agent, as well as the death ligand Apo-2L/TRAIL (tumor necrosis factor-alpha-related apoptosis-inducing ligand) induce the mitochondrial release and cytosolic accumulation of Smac/DIABLO, along with cyt c, in human acute leukemia Jurkat T cells. While it had no activity alone, ectopic overexpression of Smac/DIABLO or treatment with the N-terminus heptapeptide (Smac-7) or tetrapeptide (Smac-4) of Smac/DIABLO significantly increased Epo B- or Apo-2L/TRAIL-induced processing and PARP cleavage activity of caspase-3. This produced a significant increase in apoptosis of Jurkat cells (P <.05). Increased apoptosis was also associated with the down-regulation of XIAP, cIAP1, and survivin. Along with the increased activity of caspase-3, ectopic overexpression of Smac/DIABLO or cotreatment with Smac-4 also increased Epo B- or Apo-2L/TRAIL-induced processing of caspase-8 and Bid, resulting in enhanced cytosolic accumulation of cyt c. This was not due to increased assembly and activity of Apo-2L/TRAIL-induced DISC (death-inducing signaling complex) but dependent on the feedback activity of caspase-3. These findings demonstrate that cotreatment with the N-terminus Smac/DIABLO peptide is an effective strategy to enhance apoptosis triggered by the death receptor or mitochondrial pathway and may improve the antitumor activity of Apo-2L/TRAIL and Epo B.

Antineoplastic Agents↗
PubMedDate not supplied

Thinking strategically about imaging capacity and capital.

Diagnostic imaging continues to place high demands on hospital and health system capital budgets due to the high cost of most equipment and the rate of technological change. Diagnostic imaging also can be a significant service in competitive positioning, both alone and in conjunction with other programs and services. The purpose of this article is to provide a framework for linking diagnostic imaging to key hospital programs, and for forecasting future demands and capital requirements. The model has been developed over time in a number of settings in the United States and Canada. The specific examples are mostly from the Seton Healthcore Network in Austin, TX.

Capital Financing↗