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Biomedical subjects

J R Duncan

Publications and source records attributed to J R Duncan.

At least 37 records · Page 2Linked to original sources
PubMed1997

Results of the 1996 survey of the American Association of Academic Chief Residents in Radiology.

RATIONALE AND OBJECTIVES: Diagnostic radiology chief residents were surveyed on issues related to residency training to compare features and gauge trends in training. METHODS: Questionnaires were mailed to accredited programs in the United States. A variety of demographic and common-interest questions were asked. RESULTS: Forty-three percent of surveys were returned. The percentage of female residents was similar to that reported in other recent surveys; however, the percentage of women among 1st-year residents had decreased. Resident salaries had increased, although the average salary for a 4th-year resident had decreased when adjusted for inflation. Most 1st-year residents started participating in overnight hospital coverage by their 12th month of residency, and the total number of call days during residency correlated inversely with the size of the residency program. Almost half of residency programs used a night-float resident to provide after-hours coverage. CONCLUSION: The information derived from the survey should be useful for program evaluation and future planning.

Fellowships and Scholarships↗
PubMed1997

Acute auto immune haemolytic anaemia secondary to hepatitis A infection.

Auto immune haemolytic anaemia has been described in association with a variety of hepatotropic viruses, in particular cytomegalovirus, Epstein-Barr virus and hepatitis B. There is a well-recognized association between chronic active hepatitis and auto immune haemolytic anaemia. We present the first reported case of acute hepatitis A which resulted in a fall in haemoglobin concentration from 14.6 to 4.5 g/dl due to an acute haemolytic anaemia with an associated rise in bilirubin from 149 to 960 mumol/l.

Acute Disease↗
PubMed1996

Portal branch occlusion safely facilitates in vivo retroviral vector transduction of rat liver.

Hepatic gene therapy might correct the clinical manifestations of several genetic disorders in patients. Although retroviral vectors with a strong liver-specific promoter can result in stable and therapeutic levels of expression of genes from the liver, application of these techniques in humans is limited by the need to perform one or more invasive procedures to achieve ex vivo or in vivo transduction of hepatocytes. In vivo delivery involves injection of retrovirus into the portal vein during liver regeneration. Although transduction is efficient and specific for the liver, induction of hepatocyte replication requires a 70% partial hepatectomy or administration of a liver toxin. An alternative method for inducing hepatocyte replication is to occlude branches of the portal vein. This results in apoptosis of hepatocytes in the occluded lobes and compensatory replication of the hepatocytes in the nonoccluded lobes. We demonstrate here that portal branch occlusion is nearly as effective as partial hepatectomy at facilitating retroviral vector transduction in vivo and has a lower morbidity. Portal branch occlusion could be performed in larger animals by minimally invasive techniques and has been used safely to treat human patients with liver cancer. Portal branch occlusion might ultimately be used in humans to facilitate retroviral vector transduction in vivo for the treatment of genetic diseases.

Alanine Transaminase↗
PubMed1996

The role of adenylate cyclase, cAMP and PGE2 in the in vitro growth regulation of murine melanoma cells by vitamin E.

Previous studies have shown that vitamin E supplementation inhibits murine melanoma cell growth in vitro. In this study, malignant murine melanoma (BL6) and non-malignant monkey kidney (LLCMK) cells were supplemented with 1-10 micrograms/ml D-alpha-tocopherol acid succinate (vitamin E succinate). The effect of vitamin E succinate supplementation on growth as well as the levels of adenylate cyclase activity, prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP) were determined in these cells. Results from these studies indicated a significant inhibition of BL6 cell growth at 5 (P < 0.025), 7 and 10 micrograms/ml (P < 0.001) vitamin E succinate supplementation, while LLCMK cells showed no significant increase or decrease in growth following vitamin E succinate supplementation. BL6 cells supplemented with 7 and 10 micrograms/ml vitamin E succinate showed a marked increase in PGE2 levels, with a significant increase (P < 0.025) occurring at 10 micrograms/ml. Adenylate cyclase activity in BL6 cells was also significantly increased at vitamin E succinate concentrations of 7 (P < 0.05) and 10 micrograms/ml (P < 0.05), respectively, and supplementation of these cells with 5 (P < 0.05), 7 and 10 micrograms/ml (P < 0.001) vitamin E succinate resulted in a significant increase in the levels of cAMP, while LLCMK cells showed no significant increase or decrease in PGE2, adenylate cyclase activity or cAMP levels over the vitamin concentrations tested.

Adenylyl Cyclases↗
PubMed1996

Results of the 1994 survey of the American Association of Academic Chief Residents in Radiology.

RATIONALE AND OBJECTIVES: Radiology chief residents are surveyed annually and the data are used to improve the training of diagnostic radiology residents. METHODS: Questionnaires were mailed to accredited programs in the United States and Canada. A variety of demographic and common-interest questions were asked. For the first time, an individual resident questionnaire also was included. RESULTS: Completed surveys from 53 programs (42%) were returned. The percentage of female residents was similar to that reported in other recent surveys. Resident salaries continued to increase. Residency selection remained highly competitive. Residents indicated that the utility of a fellowship in radiology exceeded the utility of clinical training in other fields prior to the radiology residency. Residents agreed with recommendations by the American Association of Academic Chief Residents in Radiology concerning proposed changes in the American Board of Radiology (ABR) examinations. CONCLUSION: The information derived from the surveys on resident selection, the utility of preradiology clinical training, and the ABR examination may be useful for residents, program directors, and departmental chairs.

Female↗
PubMed1996

Accuracy of interpretation of microscopic images of cytologic, hematologic, and histologic specimens using a low-resolution desktop video conferencing system.

OBJECTIVE: To determine the accuracy of interpretation of microscopic images for pathologic study transmitted over Switched-56 lines using a desktop interactive video conferencing system. MATERIALS AND METHODS: In subjective studies, two systems were connected using null-modem cables, which allowed evaluation of different bandwidths from 56 kbps to 384 kbps. Objective studies were done with two systems connected at distant sites via paired Switched-56 lines that produced an effective bandwidth of 112 kbps. A video camera mounted on a microscope was attached to the sending system. The resolution of the video image on the video conferencing system was 352 x 288 lines. Cases for cytology, hematology, and histopathology studies were selected from archives; one pathologist transmitted microscopic images, and a second pathologist made interpretations. The three pathologists were Board certified with similar experience that ranged from 20 to 35 years. Categories of interpretations or observations were predetermined for each study to allow the data on agreement between the direct microscopic interpretation or observation and that recorded by the receiving pathologist to be corrected for agreement attributable to chance alone. The results were analyzed using the kappa statistic. RESULTS: In the subjective studies, image degradation prevented interpretation while the microscope stage was moved. This problem occurred at all bandwidths tested. Image quality limited microscopic details. Organisms < 1 micron in diameter could not be seen reliably. In objective cytologic studies, overall agreement was recorded on 89 of 99 observations. In the four categories of specimens, observed agreement ranged from 0.778 to 0.958, and kappa was 0.704 to 0.948. For hematology specimens, overall agreement was found on 69 of 80 observations; observed agreement on eight types of nucleated blood cells ranged from 0.5 to 1.0, and kappa was 0.429 to 1.0. Poorer color definition and image quality prevented accurate identification of lymphoblasts and eosinophils in particular. For histologic specimens, overall agreement was obtained on 56 of 66 observations, observed agreement on four categories of histologic change ranged from 0.73 to 0.93, and kappa was 0.47 to 0.9. CONCLUSIONS: The desktop interactive video conferencing system, as configured in this study, was unsuitable for making definitive diagnoses from transmitted microscopic images.

Cell Biology↗
PubMed1995

Identification of metabolites of 111In-diethylenetriaminepentaacetic acid-monoclonal antibodies and antibody fragments in vivo.

The in vivo fate of various 111In-labeled polypeptides has been the subject of many investigations. Intracellular metabolism has been studied through the use of 111In-labeled glycoproteins that are concentrated in the lysosome by receptor-mediated endocytosis. These studies have indicated that the main lysosomal metabolite is 111In-chelate-epsilon-lysine, both in vitro and in vivo (Y. Arano et al., J. Nucl. Med., 35: 890-898, 1994; F. N. Franano et al., Nucl. Med. Biol., 21: 1023-1034, 1994). Since the vast majority of radiolabeled antibodies do not localize within the target tissue, an understanding of the metabolism of 111In-labeled antibodies in nontarget tissues is important for the rational design of future radiolabeled antibodies. We investigated the in vivo metabolism of 111In-DTPA3-conjugated antibody in female Sprague-Dawley rats using the anticolorectal carcinoma monoclonal antibody (MAb) 1A3 and MAb 1A3-F(ab')2. Livers and kidneys were harvested from rats injected with either intact MAb or MAb fragments and analyzed by gel filtration chromatography. Thirty-five % of the radioactivity from 111In-DTPA-1A3 MAb present in the liver was in the form of a low molecular weight species at 1 through 5 days. In contrast, 111In-DTPA-1A3-F(ab')2 was > 98% degraded to a low molecular weight species in the kidney after 1 day. In each case, the low molecular weight metabolites were collected and further analyzed by silica gel thin-layer chromatography, reversed phase high-performance liquid chromatography, and ion-exchange chromatography and compared to 111In-DTPA and 111In-DTPA-epsilon-lysine standards. In each system, the major metabolite co-eluted with 111In-DTPA-epsilon-lysine, similar to the results obtained with 111In-labeled glycoproteins that are delivered to lysosomes by receptor-mediated endocytosis. A minor metabolite that was more highly charged than 111In-DTPA was also observed. Analysis of urine and feces demonstrated that the main excretory product of both 111In-labeled intact 1A3 and 1A3-F(ab')2 was 111In-DTPA-epsilon-lysine. Based on this data, we propose that 111In-DTPA-antibodies are degraded within lysosomes of nontarget organs such as the liver and kidneys.

Animals↗
PubMed1995

Influence of antioxidants on cadmium toxicity of mouse preimplantation embryos in vitro.

To test the hypothesis that the developmental toxicity of cadmium (Cd) is due in part to oxidative damage, embryos were cultured in medium containing 0.0, 1.0, 3.0, or 6.0 microM Cd with or without various antioxidants for 72 h. Ascorbate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and glutathione (GSH) were all effective at ameliorating 1.0 microM Cd-induced embryotoxicity. For embryos cultured in medium containing either 3.0 or 6.0 microM Cd, GSH was effective at ameliorating Cd toxicity while the other antioxidants tested were ineffective. Pretreating embryos with antioxidants for 24 h prior to exposing them to Cd and antioxidants did not significantly alter the previously observed improvement with the exception that pretreatment with GSH virtually eliminated Cd-induced embryotoxicity between 1.0 and 6.0 microM Cd. A 4-h exposure to GSH prior to culture in Cd markedly improved embryo development suggesting that GSH taken up during pretreatment can provide protection against Cd-induced embryotoxicity. This work supports the hypothesis that the developmental toxicity of Cd is in part due to oxidative damage that can be modulated by select antioxidants.

Analysis of Variance↗
PubMed1995

Biodistribution and metabolism of targeted and nontargeted protein-chelate-gadolinium complexes: evidence for gadolinium dissociation in vitro and in vivo.

The intracellular metabolism of receptor-targeted 153Gd-DTPA-glycoproteins was studied in vitro and in vivo. These agents bound to cell surface receptors, underwent receptor mediated endocytosis, and were rapidly degraded to a metabolite which co-migrated with a 153Gd-DTPA-lysine standard on thin layer chromatography. The rates of dissociation of 153Gd and 111In from a glycoprotein-chelate conjugate were determined in vitro. Gadolinium readily dissociated, in a pH-sensitive manner, from glycoprotein-DTPA, and to a lesser degree glycoprotein-MX-DTPA. The biodistribution of targeted and blood pool 153Gd/111In labeled proteins also suggested that gadolinium dissociates from protein-DTPA and protein-MX-DTPA and their metabolites leading to an accumulation of gadolinium in bone. Metal-DTPA-glycoprotein agents targeted to cell surface receptors can still produce very high concentrations of radioactive or paramagnetic metals within the lysosome due to the high rate of accumulation afforded by receptor mediated endocytosis and the low release rate of metabolites such as metal-DTPA-lysine. However, the continued development of gadolinium based macromolecular agents will require improvements in bifunctional chelates.

Animals↗
PubMed1995

Phospholipase A2 activity in vitro cultured cells--influence of ascorbate supplementation.

Non-malignant LLCMK cells and malignant B16 cells were supplemented with ascorbate, over the concentration range 0-100 micrograms/ml ascorbate. The effects of ascorbate supplementation on cell growth and phospholipase A2 activity of the membrane fractions of the respective cell lines were determined. Increasing ascorbate supplementation had a significant inhibitory effect on the growth of the B16 cells. Phospholipase A2 activity in the control B16 cells was lower than that detected in the control LLCMK cells. Phospholipase A2 activity decreased significantly in the B16 cells upon increasing ascorbate supplementation, while the supplementation of ascorbate to the LLCMK cells did not have any significant effect on phospholipase A2 activity in these cells.

Animals↗
PubMed1994

Interrelationship of ascorbate, arachidonic acid and prostaglandin E2 in B16 melanoma cells.

Previous studies have shown that ascorbate (Asc) supplementation affects arachidonic acid (AA) and prostaglandin E2 (PGE2) levels in B16 murine melanoma cells. In this study, non-malignant LLCMK cells and malignant B16 cells were respectively supplemented with 20 microCi 15-3H AA, to investigate whether these two cell types were able to take up AA from the media. Furthermore, these cells were also supplemented with Asc (0-100 micrograms/ml) to determine the effect of Asc supplementation on 15-3H AA uptake. Both cell types incorporated 15-3H AA, while Asc supplementation enhanced this 15-3H AA uptake. To determine the site of the AA incorporation, both cell types were supplemented with 2.5 microM AA and Asc (0-100 micrograms/ml). The % AA composition of the stroma fractions of both cell types was increased with 100 micrograms/ml Asc supplementation. Supplementation of these cells with AA (0-50 microM) resulted in an increase in PGE2 levels in the B16 cells. Since PGE2 has been shown, in turn, to stimulate adenylate cyclase (AC) activity, the LLCMK and B16 cells were supplemented with 0-100 microM PGE2. A 3-fold increase of AC activity in the B16 cells occurred as a result of this supplementation.

Adenylyl Cyclases↗
PubMed1994

Metabolism of receptor targeted 111In-DTPA-glycoproteins: identification of 111In-DTPA-epsilon-lysine as the primary metabolic and excretory product.

The hepatic and renal retention of indium-111 (111In) from 111In-labeled polypeptides has been the subject of many investigations. Because the lysosome is a common intracellular destination for the degradation of polypeptides, we studied the lysosomal metabolism of 111In-DTPA-labeled glycoproteins targeted to cell surface receptors in vitro and in vivo. We found that 111In-DTPA-glycoproteins were degraded to 111In-DTPA-epsilon-lysine, which was slowly released from cells and recovered intact in urine and feces. These results suggest a mechanism for 111In retention at target and non-target sites.

Animals↗
PubMed1993

The effect of ascorbate on essential fatty acid composition in B16 melanoma cells.

Ascorbate has been shown to be involved in essential fatty acid (EFA) metabolism, resulting in the suggestion that the effect of ascorbate on cell growth may be mediated through an influence on the metabolism of these FAs. This study examined the effect of ascorbate, supplemented over the nutritional concentration range of 0-100 micrograms/ml, on the in vitro cell growth of non-malignant LLCMK (monkey kidney) cells and malignant B16 murine melanoma cells. The effect of ascorbate on EFA composition was also investigated, and involved the determination of the levels of linoleic acid (LA), gamma-linoleic acid (GLA), dihomogammalinolenic acid (DGLA) and arachidonic acid (AA) present in the stroma and membrane of the two cell types. Ascorbate had no significant inhibitory or stimulatory effect on the growth of either the LLCMK or B16 cells. EFA levels detected in the LLCMK cells were generally higher than those detected in the B16 cells. The % composition of the various EFAs in the stroma fractions of the two cell types were higher than the level of the corresponding EFAs in the membrane fractions. GLA levels were not detectable in the membrane fractions of the B16 cells. AA % composition determined in both cell types, was greater than that of any other EFA % composition.

Animals↗
PubMed1993

Structural and serological specificities of Pasteurella haemolytica lipopolysaccharides.

Lipopolysaccharides (LPSs) from 16 serotypes of Pasteurella haemolytica were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and examined by silver staining and immunoblotting. Silver staining of proteinase K-digested cell lysates revealed two rough LPS serotypes (serotypes 2 and 8), which lacked demonstrable O-polysaccharide, while 14 others demonstrated a ladder pattern characteristic of smooth-type LPS. Purified LPSs from several serotypes yielded O-polysaccharide in addition to low-molecular-weight core oligosaccharide components when subjected to mild acid hydrolysis. Nuclear magnetic resonance spectroscopy revealed the O-chain polysaccharides of serotypes 1, 6, and 9 to be identical. Immunoblots using hyperimmune rabbit, mouse, bovine, and ovine sera from homologous and heterologous serotypes supported this finding and suggested that most of the A biotypes share common O-chain epitopes. Immunoblotting results also supported structural data which demonstrated that the O-polysaccharides of serotypes 3 and 15 and of serotypes 4 and 10 (T biotypes) are identical. Nuclear magnetic resonance analysis indicated that the core oligosaccharides of serotypes 1, 6, 8, 9, and 12 share similar structures, but that they are distinct from those of serotypes 3, 4, 10, and 15. Immunoblots with hyperimmune antisera and monoclonal antibody having specificity for the core region of serotype 1 LPS revealed shared epitopes in the core oligosaccharides of several A biotypes. Characterization of the molecular structure and antigenic specificities of LPS has been an important consideration in the development of purity and potency assays for veterinary vaccines which contain P. haemolytica.

Antigens, Bacterial↗