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Biomedical subjects

J E Lee

Publications and source records attributed to J E Lee.

At least 19 recordsLinked to original sources
PubMed2003

Pancreatic leak after left pancreatectomy is reduced following main pancreatic duct ligation.

BACKGROUND: Although much is known about the long-term outcome of patients undergoing left (distal) pancreatectomy for malignancy, comparatively little is known about the optimal management strategy for the residual transected pancreatic parenchyma and the divided pancreatic duct. Clinicopathological and operative factors that may contribute to postoperative pancreatic leak were evaluated. METHODS: A retrospective review of the medical records of 126 patients who underwent left pancreatectomy between June 1990 and December 1999 at the University of Texas M. D. Anderson Cancer Center was performed. RESULTS: Indications for left pancreatectomy included pancreatic neoplasms (n = 42; 33.3 per cent), en bloc resection for management of retroperitoneal sarcoma (n = 21; 16.7 per cent), gastric adenocarcinoma (n = 14; 11.1 per cent), renal cell carcinoma (n = 11; 8.7 per cent) and other tumours or benign conditions (n = 38; 30.2 per cent). Pancreatic parenchymal closure was accomplished by a hand-sewn technique, mechanical stapling, or a combination of the two in 83, 20 and 15 patients respectively. No form of parenchymal closure was used in eight patients. Identification of the pancreatic duct and suture ligation was performed in 73 patients (57.9 per cent). Twenty-five patients (19.8 per cent) developed a pancreatic leak. For subgroups having duct ligation or no duct ligation, pancreatic leak rates were 9.6 per cent (seven of 73 patients) and 34.0 per cent (18 of 53 patients) respectively (P < 0.001). Multivariate analysis including clinicopathological and operative factors indicated that failure to ligate the pancreatic duct was the only feature associated with an increased risk for pancreatic leak (odds ratio 5.0 (95 per cent confidence interval 2.0 to 10.0); P = 0.001). CONCLUSION: Pancreatic leak remains a common complication after left pancreatectomy. The incidence of leak is reduced significantly when the pancreatic duct is identified and directly ligated during left pancreatectomy.

Adenocarcinoma↗
PubMed2003

Intermediate filament nestin expressions in human cord blood monocytes (HCMNCs).

OBJECTS: Nestin is an intermediate protein and a well-known specific neural stem cell antigen. Some bone marrow stem cells can generate not only blood cells but also neurons and glial cells under specific culture conditions. Furthermore, in vitro cultured bone marrow stem cells also express nestin antigen. However, it is unclear whether cord blood cells also differentiate into neural cells or not. In this study, we investigated the expression of nestin on human cord blood monocytes (HCMNCs) and we discuss the relevance of this finding upon future therapeutic applications of HCMNCs in neurological diseases. METHODS: HCMNCs were prepared from normal placenta after full-term normal delivery. Immunocytochemical staining and reverse transcriptase polymerase chain reaction (RT-PCR) for nestin and CD133 antigen were performed to confirm nestin and CD133 antigen expression in the HCMNCs. RESULTS: Some nestin expressing HCMNCs were found. Immunocytochemical staining showed that some of the blood stem cell marker CD133 expressing cells co-expressed nestin. RT-PCR demonstrated nestin and CD133 mRNA in HCMNCs, but not in adult blood monocytes. Approximately, 60 +/- 8% of CD133 expressing cells expressed nestin. CONCLUSION: In the present study, we found that more than 60% of CD133 expressing HCMNCs also express nestin antigen in their cytoplasm, which supports the idea that cord blood stem cells can adopt a neuronal fate.

AC133 Antigen↗
PubMed2003

Stroke: molecular mechanisms and potential targets for treatment.

Significant advances have been made over the past few years concerning the cellular and molecular events underlying ischemic cell death. The brain succumbs to ischemic injury as a result of loss of metabolic stores, excessive intracellular calcium accumulation, oxidative stress, and potentiation of the inflammatory response. Neurons can also die via necrotic or apoptotic mechanisms, depending on the nature and severity of the insult. While it has been widely held that ischemia is notable for cessation of protein synthesis, brain regions with marginal reduction in blood supply are especially capable of expressing a variety of genes, the functions of many of which are only beginning to be understood. Gene expression is also upregulated upon reperfusion and reoxygenation. As a result, a number of signaling pathways have been identified and are now known to contribute to ischemic progression or, in some cases, attempts at self preservation. This review will focus on the roles of stress genes, apoptosis-related genes, and inflammation. Knowledge of such molecular events has fueled interest in developing specific molecular targets with the hope of someday affecting outcome in clinical stroke.

Animals↗
PubMed2002

Identification of differentially expressed mRNA during pancreas regeneration of rat by mRNA differential display.

Pancreatectomy (Px) is known to cause islet hypertrophy and is a putative method to mimic hyperglycemia representing type II diabetes mellitus. Therefore, finding new genes related to pancreatectomy will help to understand the molecular mechanism of hypertrophy and hyperglycemia, and may provide new diagnostic markers of type II diabetes. To this end, mRNA differential display was used to isolate genes that show transcriptional changes in pancreas of rat after 90% partial pancreatectomy. Forty-nine candidate pancreas regeneration-associated transcripts were isolated. cDNA sequencing and subsequent database analysis revealed that 15 transcripts showed no significant sequence similarity to previously reported genes, whereas 34 transcripts showed significant similarity with genes deposited in the GenBank. The differential mRNA expression of 49 transcripts was confirmed using screening of slot blots and Northern blot analysis was performed to several genes. It was noteworthy that the Wnt-1 inducible signaling pathway protein-1 (WISP-1), Ras-associated protein 1B (Rap1B), vascular cell adhesion molecule-1 (VCAM-1), and huntingtin interacting protein genes (HIP) were observed to be over-expressed during pancreas regeneration. Several genes' expression was modified by pancreatectomy. Profiling of gene expression in response to pancreatectomy may lead to new insights into hypertrophy and hyperglycemia representing type II diabetes, as well as into the identification of novel diagnostic markers of type II diabetes.

Animals↗
PubMed2002

Is the therapeutic index better with gemcitabine-based chemoradiation than with 5-fluorouracil-based chemoradiation in locally advanced pancreatic cancer?

PURPOSE: To retrospectively compare the toxicity and efficacy of concurrent gemcitabine-based chemoradiation with that of concurrent 5-fluorouracil (5-FU)-based chemoradiation in patients with unresectable pancreatic cancer. PATIENTS AND METHODS: Between September 1996 and May 2000, 114 patients with localized unresectable adenocarcinoma of the pancreas were treated with concurrent chemoradiation. Locally advanced unresectable disease was defined as low-density tumor in contact with the superior mesenteric artery (SMA) or celiac artery, or occlusion of the superior mesenteric-portal venous confluence. Fifty-three patients were selected to receive gemcitabine in 7 weekly cycles (250-500 mg/m(2)) with concurrent radiotherapy (median dose 30 Gy, range 30-33 Gy in 10-11 fractions). The remaining 61 patients received continuous-infusion 5-FU (200-300 mg/m(2)) with concurrent radiotherapy (30 Gy in 10 fractions). Radiotherapy was delivered to the primary tumor and regional lymphatics. Patients receiving gemcitabine and those receiving 5-FU had a similar mean Karnofsky performance status (KPS, 89% vs. 86%), distribution of tumor grade (43% vs. 33% poorly differentiated), and percent weight loss (all p = NS). However, patients treated with gemcitabine had a significantly larger median maximum cross-sectional tumor area (TA, 8.8 cm(2) vs. 5.7 cm(2), p = 0.046) and were significantly younger (median age 60 vs. 68 years, p <0.001). Severe acute toxicity (ST) was defined as toxicity requiring a hospital stay of more than 5 days, mucosal ulceration with bleeding, more than 3 dose deletions of gemcitabine or discontinuation of 5-FU, or toxicity resulting in surgical intervention or death. Kaplan-Meier analysis was used to calculate the actuarial rate of local progression on imaging (LP), the rate of distant metastasis (DM), and the overall survival (OS) rate. The imaging was reviewed in resected patients. RESULTS: Patients receiving gemcitabine developed significantly more ST during treatment (23% vs. 2%, p < 0.0001) than did those receiving 5-FU. Patients treated with gemcitabine had a similar 10-month LP rate (62% vs. 61%), 10-month DM rate (55% vs. 47%), 1-year OS rate (42% vs. 28%), and median OS duration (11 months vs. 9 months) to patients treated with 5 FU (all p = NS). Five patients who received gemcitabine and 1 patient who received 5-FU underwent margin-negative pancreaticoduodenectomy after chemoradiation. Three patients had a short segment ( 10 cm(2) (p = 0.03) and poor differentiation (p = 0.07) were associated with a worse survival duration; however, other factors, such as KPS and weight loss >10% and age did not influence OS. CONCLUSION: Despite the selection of healthier patients to receive gemcitabine, there was a significantly higher severe toxicity rate than with 5-FU. The median and 1-year survivals were not significantly different with the use of concurrent gemcitabine; however, the tumors treated were significantly larger. Additionally, a small number of patients with minimal arterial involvement whose disease met our radiographic definition of unresectable disease had margin-negative resections after treatment with gemcitabine-based chemoradiation. These possible benefits and the high rate of severe toxicity define a very narrow therapeutic index for concurrent gemcitabine-based chemoradiation given by this schedule of administration.

Adenocarcinoma↗
PubMed2002

Dietary arginine intake alters avian leukocyte population distribution during infectious bronchitis challenge.

Although dietary arginine is a factor in immune function and disease resistance, the full range of effects has yet to be described. In this study, the effects of dietary arginine on leukocyte population changes were examined in the peripheral blood and the respiratory tract of chickens inoculated with infectious bronchitis virus (IBV) strain M41. At 2 wk of age, female line P2a White Leghorn-type chickens were randomly assigned to one of three diets with different arginine levels: a marginally deficient diet (0.5%), an adequate diet (1.0%), and a diet containing a high level of arginine (3.0%). All birds were inoculated with IBV at 4 wk of age, and then the peripheral blood and the respiratory lavage were collected at 1 and 7 d postinfection (DPI). The growth rate of birds that received 0.5% arginine was significantly lower than that of birds receiving 1.0 or 3.0% arginine, whereas the growth of the latter groups did not differ. The percentage and absolute number of heterophil (H) and the H/lymphocyte (L) ratio in the peripheral blood at 1 DPI significantly increased as dietary arginine increased. In the respiratory lavage at 1 DPI, the percentage of H also increased with dietary arginine increase. At 7 DPI, the percentage of CD8+ cells from birds fed the deficient diet was lower than those from birds fed the adequate diet and the diet containing a high level of arginine, whereas the cell surface density of CD8 antigen did not vary among groups. These results show that dietary arginine influences the character of the chicken cellular response to IBV and the distribution of responding leukocyte subpopulations in a target tissue for the infection.

Animal Feed↗
PubMed2002

Application of recombinant fluorescent mammalian cells as a toxicity biosensor.

With respect to developing a more sensitive biosensor, a recombinant fluorescent Chinese Hamster Ovary cell line was used for the monitoring of various toxicants. Both cell lines, EFC-500 and KFC-A10, were able to detect toxicants sensitively. They were characterized with mitomycin C and gamma-ray as genotoxicants and bisphenol A, nonylphenol, ziram and methyl bromide as possible and known EDCs. When compared to each other, the response of KFC-A10 was generally more informative and sensitive. Compared to typical bacterial biosensor systems, these cell lines offered a sensitivity of 2- to 50-fold greater for the tested chemicals. Based on these results, the use of mammalian cells offers a sensitive biosensor system that is not only fast, cheap and reproducible but also capable of monitoring the endocrine-like characteristics of environmental toxicants.

Animals↗
PubMed2001

The structure of L-ribulose-5-phosphate 4-epimerase: an aldolase-like platform for epimerization.

The structure of L-ribulose-5-phosphate 4-epimerase from E. coli has been solved to 2.4 A resolution using X-ray diffraction data. The structure is homo-tetrameric and displays C(4) symmetry. Each subunit has a single domain comprised of a central beta-sheet flanked on either side by layers of alpha-helices. The active site is identified by the position of the catalytic zinc residue and is located at the interface between two adjacent subunits. A remarkable feature of the structure is that it shows a very close resemblance to that of L-fuculose-1-phosphate aldolase. This is consistent with the notion that both enzymes belong to a superfamily of epimerases/aldolases that catalyze carbon-carbon bond cleavage reactions via a metal-stabilized enolate intermediate. Detailed inspection of the epimerase structure, however, indicates that despite the close overall structural similarity to class II aldolases, the enzyme has evolved distinct active site features that promote its particular chemistry.

Aldehyde-Lyases↗
PubMed2001

Involvement of a post-transcriptional mechanism in the inhibition of CYP1A1 expression by resveratrol in breast cancer cells.

Resveratrol decreases basal and induced CYP1A1 mRNA/protein levels in both in vitro and in vivo models, and some studies suggest that resveratrol acts as an aryl hydrocarbon receptor (AhR) antagonist. Treatment of T47D or MCF-7 cells with 10 microM resveratrol inhibited induction of CYP1A1 mRNA and CYP1A1-dependent activity after treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), as previously reported. In contrast, resveratrol did not inhibit TCDD-induced reporter gene activity in cells transfected with an Ah-responsive construct containing a human CYP1A1 gene promoter insert, whereas 3'-methoxy-4'-nitroflavone, a "pure" AhR antagonist, inhibited this response. Resveratrol induced transformation of the rat cytosolic AhR and, after treatment of T47D and MCF-7 cells with resveratrol, a transformed nuclear AhR complex was observed. In contrast to 3'-methoxy-4'-nitroflavone, resveratrol did not block TCDD-induced AhR transformation in vitro or nuclear uptake of the AhR complex in breast cancer cells. Thus, the action of resveratrol on the AhR was consistent with that of an AhR agonist; however, resveratrol did not exhibit functional AhR agonist or antagonist activities in breast cancer cells. Actinomycin D chase experiments in T47D cells showed that resveratrol and dehydroepiandrosterone both increased the rate of CYP1A1 mRNA degradation, whereas resveratrol did not affect CYP1A1-dependent activity in cells pretreated with TCDD for 18 hr. These data suggest that resveratrol inhibits CYP1A1 via an AhR-independent post-transcriptional pathway.

Antineoplastic Agents, Phytogenic↗
PubMed2001

An essential histidine residue in GTP binding domain of bovine brain glutamate dehydrogenase isoproteins.

Greater than 90% of the original activity of the enzymes remained after modification of histidine residues of glutamate dehydrogenase (GDH) isoproteins from bovine brains with diethyl pyrocarbonate (DEPC). This suggests that the DEPC modified histidine residues are not critically involved in the catalysis of the GDH isoproteins. The influence of DEPC modified histidine residue(s) on binding of GTP to GDH isoproteins was investigated by protection studies. These studies showed that inhibition of GDH isoproteins by GTP was protected by preincubation of GDH isoproteins with DEPC. The amount of protection was dependent on the concentration of DEPC. The GTP inhibition was fully protected by preincubation of GDH isoproteins with DEPC at saturating concentrations. These results indicate that the histidine residues may play an important role in the GTP binding on GDH isoproteins. Spectrophotometric studies showed that three histidine residues per enzyme subunit were able to react with DEPC in the absence of GTP, whereas two histidine residues per enzyme subunit interacted with DEPC when the enzymes were preincubated with GTP. These results indicate that one of the histidine residues is involved in the GTP binding domain of GDH isoproteins. The quantitative affinity chromatographic studies showed that the influence of GTP on the binding of GDH isoproteins to DEPC-Sepharose was significantly distinct for the two GDH isoproteins. GDH I was more sensitively affected by GTP than GDH II in the binding affinity for DEPC-Sepharose. ADP, another well-known allosteric regulator, showed no significant changes in the interaction of DEPC with GDH isoproteins.

Adenosine Triphosphate↗
PubMed2001

MPP(+) downregulates mitochondrially encoded gene transcripts and their activities in dopaminergic neuronal cells: protective role of Bcl-2.

The effects of neurotoxins on levels of mitochondrially encoded gene transcripts in a dopaminergic neuronal cell line, MN9D, were examined following treatment with 200 microM N-methyl-4-phenylpyridinium (MPP(+)) or 6-hydroxydopamine (6-OHDA). As confirmed by a Northern blot analysis, levels of cytochrome c oxidase subunit 3 (COX III) and ATPase subunit 6 (ATPase 6) transcript were decreased in a time-dependent manner following treatment with MPP(+) but not with 6-OHDA. Accordingly, enzymatic activity of cytochrome c oxidase (COX) and the intracellular ATP content were also decreased in MPP(+)-treated cells while these remained unaltered in 6-OHDA-treated cells. In the cell death paradigm induced by MPP(+), overexpression of Bcl-2 in MN9D cells (MN9D/Bcl-2) significantly blocked MPP(+)-induced downregulation of COX III and ATPase 6 transcripts. In MN9D/Bcl-2 cells, MPP(+)-induced downregulation of COX activity and the intracellular level of ATP was also blocked. Treatment with a pan-caspase inhibitor, however, neither prevented MPP(+)-induced downregulation of COX activity nor affected intracellular level of ATP in MN9D cells. Taken together, our present data suggest that Bcl-2 may play a regulatory role in energy metabolism by preventing downregulation of mitochondrially encoded gene(s) at a point distinct from its known anticaspase activity in MPP(+)-induced dopaminergic neuronal death.

1-Methyl-4-phenylpyridinium↗
PubMed2001

Differential roles of cyclooxygenase isoforms after kainic acid-induced prostaglandin E(2) production and neurodegeneration in cortical and hippocampal cell cultures.

Prostaglandins, which are cyclooxygenase (COX) products, are pathologically up-regulated, and have been proven to be closely associated with neuronal death. In this study, we investigated a role of COX isoforms (COX-1 and COX-2) in kainic acid-induced neuronal death in cultured murine cortical or hippocampal neurons. In primary cortical neurons, both indomethacin (COX-1/-2 nonselective inhibitor) and aspirin (COX-1 preferential inhibitor) reduced basal and kainic acid-induced PGE(2) production significantly and prevented neuronal cell death after kainic acid treatment. In contrast, NS398 (COX-2 selective inhibitor) had no effect on kainic acid-induced neuronal cell death. In hippocampal neurons, however, COX-2 inhibitors prevented both kainic acid-induced neuronal death and PGE(2) production. COX-2 expression was remarkably up-regulated by kainic acid in hippocampal neurons; whereas in cortical neurons, COX-2 expression was comparatively less significant. Astrocytes were unresponsive to kainic acid in terms of PGE(2) production and cell death. In conclusion, we suggest that the release of PGE(2) induced by kainic acid occurred through COX-1 activity rather than COX-2 in cortical neurons. The inhibition of PGE(2) release by COX-1 inhibitors prevented kainic acid-induced cortical neuronal death, while in the hippocampal neurons, COX-2 inhibitors prevented kainic acid-induced PGE(2) release and hippocampal neuronal death.

Animals↗
PubMed2001

Induction of histone acetylation in mouse erythroleukemia cells by some organosulfur compounds including allyl isothiocyanate.

In previous studies we observed that some allyl sulfides can cause increased acetylation of histones and differentiation in DS19 mouse erythroleukemia cells. In the present work we observed increased acetylation of histones with allyl isothiocyanate and butanethiol but not with butyl sulfide or butyl disulfide. Increased acetylation of histones was established by change in electrophoretic mobility, incorporation of [3H]acetate or immunoblotting. Histone deacetylase in nuclei of DS19 cells was inhibited 74% by 0.5 mM allyl mercaptan and 43% by 0.5 mM butanethiol but was not significantly affected by 0.5 mM allyl isothiocyanate. There was some degree of reversibility in the effect of allyl isothiocyanate when the cells were incubated for 15 hr in fresh medium. The data suggested that allyl isothiocyanate may stimulate histone acetylation rather than inhibit histone deacetylation. Addition of allyl isothiocyanate, however, had very little or no additional effect on the induction of histone acetylation caused by trichostatin A. Histone acetyltransferase activity determined in cell homogenates was not increased by preincubation of cells with allyl isothiocyanate or inclusion of allyl isothiocyanate in the assay medium. It was concluded that treatment of mouse erythroleukemia cells with allyl isothiocyanate can cause increased acetylation of histones but the mechanism for this effect requires further elucidation.

Acetylation↗
PubMed2001

Compaction in preimplantation mouse embryos is regulated by a cytoplasmic regulatory factor that alters between 1- and 2-cell stages in a concentration-dependent manner.

Present studies were performed to investigate what factors affect the morphogenesis of preimplantation mouse embryos, and to find the action mechanism of that factor by using cytoplasm removal and its reconstitution from a different developmental stage embryo. Half (HP group) or one-third of cytoplasm (TP group) was removed from 1-cell mouse embryos by micromanipulation, and their morphogenesis and genome expression were compared with sham-operated embryos (SP group). The compaction and blastocoel formation of embryos in both the HP and TP groups were accelerated in time and cell stage when compared with those of the SP group. However, the total activity and time of RNA synthesis, and gene expression of ZO-1alpha+ isoform were not different. To change the cytoplasm composition without altering the nucleus/cytoplasmic ratio, half a 1-cell embryo with both pronuclei was reconstituted with the half enucleated cytoplasm of 1-cell embryo (P + P group), 2-cell (P + 2 group) or 4-cell (P + 4 group) by electrofusion. Embryonic compaction, timing of RNA synthesis, and stage-specific gene expression of the ZO-1alpha(+) isoform in the P + 2 and P + 4 groups were accelerated in time and cell stage than that in the P + P group, but not different between the P + 2 and P + 4 groups. In addition, a blastomere of 2-cell embryo was reconstituted with the enucleated cytoplasm of 1-cell embryo (2 + P group) or 2-cell (2 + 2 group) in equal volume by electrofusion. Also, the karyoplast of 2-cell was fused with the enucleated 1-cell embryo (2 + PP group). Embryonic development, total activity of RNA synthesis, and gene expression of the ZO-1alpha(+) isoform of embryos in the 2 + P and 2 + PP groups were delayed when compared with those of the 2 + 2 group. Also, the phenomena of compaction and blastocoel formation were delayed in the development time and cell stage. From these results, the nucleus/cytoplasm ratio was found to have no direct effect on the regulation of embryonic morphogenesis, although it accelerated compaction and blastocoel formation. However, cytoplasmic factors that altered between 1- and 2-cell stages regulate embryonic morphogenesis, especially compaction, of preimplantation mouse embryos in concentration-dependent manner.

Animals↗
PubMed2001

Short heterodimer partner (SHP) orphan nuclear receptor inhibits the transcriptional activity of aryl hydrocarbon receptor (AHR)/AHR nuclear translocator (ARNT).

SHP (short heterodimer partner) is an orphan nuclear receptor lacking a DNA binding domain that interacts with nuclear receptors (NR) including thyroid receptor (TR), retinoic acid receptors (RAR and RXR), and estrogen receptors alpha and beta (ERalpha and ERbeta). SHP acts as a negative regulator of these receptors by inhibiting DNA binding and transcriptional activation. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) binds to arylhydrocarbon receptor (AHR), activating the AHR/AHR nuclear translocator (ARNT) heterodimer. We investigated the physical and functional interaction of SHP with AHR/ARNT. In RL95-2 human endometrial carcinoma cells, SHP inhibited TCDD-stimulated reporter activity from the AHR-responsive CYP1A1 and UGT1A6 gene promoters in a concentration-dependent manner. In GST pull-down assays, ARNT interacted directly with SHP in vitro, but AHR did not interact with GST-SHP. SHP inhibited AHR/ARNT-DNA binding in vitro. These results identify ARNT as a novel SHP target. We speculate a role for SHP in the suppression of agonist-activated AHR/ARNT activity.

Animals↗