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Biomedical subjects

M J Lee

Publications and source records attributed to M J Lee.

At least 109 records · Page 6Linked to original sources
PubMed2000

Oxidative damage in an esophageal adenocarcinoma model with rats.

Oxidative damage has long been related to carcinogenesis in human cancers and animal cancer models. Recently a rat esophageal adenocarcinoma (EAC) model was established in our laboratory by using esophagoduodenal anastomosis (EDA) plus iron supplementation. Our previous study suggested that iron supplementation enhanced inflammation and the production of reactive nitrogen species in the esophageal epithelium, which could contribute to esophageal adenocarcinogenesis. Here we further characterized oxidative damage in this model. We were particularly interested in how excess iron was deposited in the esophagus, and which cells were targeted by oxidative damage. Male Sprague-Dawley rats received iron supplementation (50 mg Fe/kg/month, i.p.) starting 4 weeks after EDA. The animals were killed at 11, 30 or 35 weeks after surgery. EAC appeared as early as week 11 after surgery, and increased over time, up to 60% at 35 weeks after surgery. All EACs were well-differentiated mucinous adenocarcinoma at the squamocolumnar junction. Iron deposition was found at the squamocolumnar junction and in the area with esophagitis. Esophageal iron overload could result from transient increase of blood iron after i.p. injection, and the overexpression of transferrin receptor in the premalignant columnar-lined esophagus (CLE) cells. Oxidative damage to DNA (8-hydroxy-2'-deoxyguanosine), protein (carbonyl content) and lipid (thiobarbituric acid reactive substance) in the esophagus was significantly higher than that of the non-operated control. CLE cells were believed to be the target cells of oxidative damage because they overexpressed heme oxygenase 1 and metallothionein, both known to be responsive to oxidative damage. We propose that oxidative damage plays an important role in the formation of EAC in the EDA model, and a similar situation may occur in humans with gastroesophageal reflux and iron over-nutrition.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Tea and tea polyphenols in cancer prevention.

The inhibitory action of tea (Camellia sinensis) and tea components against cancer formation has been demonstrated in different animal models involving different organ sites in many laboratories. The possible preventive activity of tea against cancer in humans, however, is not clear. A critical question is whether the information obtained from animal studies is applicable to humans because of possible species differences or the difference in the quantity of tea used in animal studies and that consumed by humans. This article will discuss the results from animal studies and possible cancer inhibitory mechanisms that might be applicable to human cancer prevention. To provide a basis for more quantitative analyses of the effect of tea on carcinogenesis, the levels of tea polyphenols in blood, urine and tissue samples have been analyzed, and the pharmacokinetic properties of tea polyphenols studied. Studies with cell lines have demonstrated that tea polyphenols affect signal transduction pathways, inhibit cell proliferation and induce apoptosis, but the effective concentrations are usually much higher than those observed in blood and tissues. More mechanistic studies in these areas will help us to understand the inhibitory action of tea against carcinogenesis and provide background for evaluating the effects of tea consumption on human carcinogenesis.

Animals↗
PubMed2000

Treatment of hostile midline back wounds: an extreme approach.

The basic principles of successful wound closure remain the same: careful preoperative evaluation, removal of underlying nonviable tissue, and well-vascularized soft-tissue coverage. Many complex or "hostile" back wound closures also require stabilization of the spine and a two-layered wound closure. The use of long arteriovenous fistulas with free tissue transfer provides an additional weapon for the treatment of these complex wounds.

Arteriovenous Anastomosis↗
PubMed2000

Sphingosine-1-phosphate signaling via the EDG-1 family of G-protein-coupled receptors.

The bioactive lipid sphingosine-1-phosphate (SPP) is abundantly formed and released during the activation of platelets by thrombotic stimuli. Once exported, SPP interacts with the G-protein-coupled receptors (GPCR) of the EDG-1 family. SPP binds to EDG-1 with the dissociation constant of approximately 8 nM and induces signal transduction events such as mitogen-activated protein kinase (MAP kinase) activation, decrease of cAMP levels, remodeling of the actin cytoskeleton, among others. EDG-1 is a prototypical member of a large family of GPCRs that interact with glycero- and sphingolysolipid phosphates, namely, SPP and lysophosphatidic acid (LPA). Three other GPCRs, trivially termed EDG-3, EDG-5, and EDG-8, are also high-affinity receptors for SPP. The four SPP receptor subtypes regulate different intracellular signal transduction pathways. In vascular endothelial cells, cooperative signaling between EDG-1 and EDG-3 subtypes of SPP receptors results in adherens junction assembly, cell survival, morphogenesis into capillary-like networks, and angiogenesis. SPP acts distinctly, albeit cooperatively, with polypeptide angiogenic factors, resulting in the formation of mature neovessels. Thus SPP signaling as an extracellular mediator via the EDG-1 family of GPCRs may be a heretofore unrecognized mechanism for the regulation of angiogenesis and vascular endothelial cell function.

Evolution, Molecular↗
PubMed2000

A tetrodotoxin-producing Vibrio strain, LM-1, from the puffer fish Fugu vermicularis radiatus.

Identification of tetrodotoxin (TTX) and its derivatives produced from a Vibrio strain in the intestine of the puffer fish Fugu vermicularis radiatus was performed by thin-layer chromatography, electrophoresis, high-performance liquid chromatography, and gas chromatography-mass spectrometry, together with a mouse bioassay for toxicity. It was demonstrated that the isolated bacterium produced TTX, 4-epi-TTX, and anhTTX during cultivation, suggesting that Vibrio strains are responsible for the toxification of the puffer fish.

Animals↗
PubMed2000

Vandellia cordifolia regulated cell proliferation and cytokines production in human mononuclear cells.

Vandellia cordifolia (V. cordifolia) used for treatment inflammation in traditional Chinese medicine was selected for immunopharmacological activity test. The effects of V. cordifolia extracted fractions on human mononuclear cells (HMNC) proliferation were determined by tritiated thymidine uptake. The results indicated that VC-ME fraction suppressed HMNC proliferation activated with phytohemagglutinin (PHA) and stimulated cell cycle progression was arrested at the G0/G1 stage. The inhibitory mechanisms may involve the blocking of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production, since VC-ME suppressed IL-2 and IFN-gamma production of HMNC in a dose-dependent manner. Therefore, it is suggested that immunomodulatory agents are contained in V. cordifolia.

Adjuvants, Immunologic↗
PubMed2000

Interventional radiologic procedures: patient anxiety, perception of pain, understanding of procedure, and satisfaction with medication--a prospective study.

PURPOSE: To prospectively assess patient anxiety, understanding of the procedure being performed, perception of pain level, and satisfaction with medication given for a variety of diagnostic and therapeutic vascular and visceral (nonvascular) interventional procedures. MATERIALS AND METHODS: The authors interviewed 204 patients before and after they underwent an interventional radiologic procedure. Patients responded to a series of questions by using a visual analog scale. Patients were grouped according to (a) their level of experience with the procedure and (b) the type of procedure performed (diagnostic or therapeutic visceral procedure or diagnostic or therapeutic vascular procedure). RESULTS: Patients who had previous experience with a procedure, whether visceral or vascular, were less anxious, had more understanding, and anticipated less pain than did those who did not have experience with a procedure. Patients who had only local anesthesia for visceral biopsy experienced greater pain than did those who had both local and intravenous anesthesia. Satisfaction scores, however, were similar throughout all groups. CONCLUSION: Patients have a moderate amount of anxiety about interventional procedures and anticipate some discomfort. Most patients have a high level of satisfaction despite the amount of pain they experience during the procedure. Patients experienced with a procedure tend to have a greater understanding of the procedure and less anxiety.

Adult↗
PubMed2000

Characterization of indeterminate (lipid-poor) adrenal masses: use of washout characteristics at contrast-enhanced CT.

PURPOSE: To determine whether computed tomographic (CT) scans and attenuation measurements on contrast material-enhanced and nonenhanced CT scans could be used to characterize adrenal masses, in particular, to characterize these lesions by using adrenal washout characteristics at contrast-enhanced CT. MATERIALS AND METHODS: Eighty-six patients (49 men, 37 women; age range, 29-86 years; mean age, 72 years) with 101 adrenal lesions depicted at contrast-enhanced CT underwent delayed (mean, 9 minutes) enhanced scanning. Seventy-eight patients also underwent nonenhanced CT. Mean diameter of the benign lesions was 2.1 cm (range, 1.0-4.2 cm); mean diameter of the malignant lesions was 2.3 cm (range, 1.0-4.1 cm). Region-of-interest measurements were obtained at nonenhanced, dynamic enhanced, and delayed enhanced CT and were used to calculate a relative percentage washout as follows: 1 - (Hounsfield unit measurement on delayed image / Hounsfield unit measurement on dynamic image) x 100%. RESULTS: Ninety-nine of 101 lesions were correctly characterized as benign or malignant with a relative percentage washout threshold of 50% on delayed scans; benign lesions demonstrated more than 50% washout; and malignant lesions, less than 50% washout. Two benign lesions demonstrating less than 50% washout were characterized as benign by using conventional CT. CONCLUSION: Calculation of relative percentage washout on dynamic and delayed enhanced CT scans may lead to a highly specific test for adrenal lesion characterization, reduce the need for, and possibly obviate, follow-up imaging or biopsy.

Adenoma↗
PubMed2000

Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation.

Sphingolipid signaling pathways have been implicated in many critical cellular events. Sphingosine-1-phosphate (SPP), a sphingolipid metabolite found in high concentrations in platelets and blood, stimulates members of the endothelial differentiation gene (Edg) family of G protein-coupled receptors and triggers diverse effects, including cell growth, survival, migration, and morphogenesis. To determine the in vivo functions of the SPP/Edg signaling pathway, we disrupted the Edg1 gene in mice. Edg1(-/-) mice exhibited embryonic hemorrhage leading to intrauterine death between E12.5 and E14.5. Vasculogenesis and angiogenesis appeared normal in the mutant embryos. However, vascular maturation was incomplete due to a deficiency of vascular smooth muscle cells/pericytes. We also show that Edg-1 mediates an SPP-induced migration response that is defective in mutant cells due to an inability to activate the small GTPase, Rac. Our data reveal Edg-1 to be the first G protein-coupled receptor required for blood vessel formation and show that sphingolipid signaling is essential during mammalian development.

Animals↗
PubMed2000

Plasma and tissue levels of tea catechins in rats and mice during chronic consumption of green tea polyphenols.

To understand the relationship between tea consumption and its biological effects, plasma and tissue levels of (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), and (-)-epicatechin (EC) were measured after rats and mice were given a 0.6% green tea polyphenol preparation as the drinking fluid for different periods of time. EGC and EC levels in rat plasma increased over time and reached peak values (3 times the Day 1 values) on Day 14. Then the plasma levels of tea catechins decreased, to Day 1 values on Day 28. The plasma concentrations of EGCG were much lower than those of EGC or EC. High levels of EGC and EC were found in urine, whereas high levels of EGCG were found in feces. The changes in the urinary and fecal excretions of tea catechins could not account for the above-described changes in the plasma levels. The amounts of catechins in different tissues reflected the ingestion, absorption, and excretion pattern. When the green tea polyphenol preparation was given to mice, the "increase-and-then-decrease" pattern of catechin levels was also observed in the plasma, lung, and liver; the EGCG levels were much higher than in the rats. The results suggest that consumption of tea by rodents could induce adaptive responses affecting blood and tissue levels of tea catechins with time and that investigation of a similar phenomenon in humans is warranted.

Adaptation, Biological↗
PubMed2000

Prevalence and significance of gallbladder abnormalities seen on sonography in intensive care unit patients.

OBJECTIVE: We evaluated sonographic abnormalities of the gallbladder other than acalculous cholecystitis across a broad range of intensive care unit (ICU) patients. SUBJECTS AND METHODS: Fifty-five consecutive patients (age range, 18-94 years old; mean age, 56 years; 33 men, 22 women), who were admitted to the ICU with a variety of diagnoses, underwent sonography of the gallbladder twice a week. Patients with gallbladder calculi were excluded from the study. The gallbladder was examined for the recognized sonographic features of acalculous cholecystitis: gallbladder wall thickening, gallbladder distention, intramural gallbladder lucencies (striated gallbladder wall), pericholecystic fluid, gallbladder sludge, and Murphy's sign. These findings were correlated with clinical and laboratory parameters that are associated with acalculous cholecystitis: fever, WBC, liver function tests, levels of serum bilirubin, mechanical ventilation status, and administration of parenteral nutrition, narcotic analgesics, antibiotics, and pressor agents. RESULTS: Eleven of the 55 patients were found to have gallbladder calculi and were excluded from the study. Thirty-seven (84%) of the remaining 44 patients had at least one sonographic abnormality while in the ICU. Twenty-five (57%) of the 44 patients had as many as three abnormalities found on sonography, and six (14%) of 44 patients had four or five sonographic findings of gallbladder abnormalities while in the ICU. No statistically significant correlation was found among any of these sonographic abnormalities and the clinical and laboratory parameters. CONCLUSION: Gallbladder abnormalities are frequently seen on sonography in ICU patients, even if these patients are not suspected of having acalculous cholecystitis; therefore, sonography appears to be of limited value in diagnosing acalculous cholecystitis in ICU patients.

Adolescent↗
PubMed2000

Expression of complement inhibitor protein CD59 in human neuronal and glial cell lines treated with HIV-1 gp41 peptides.

In attempts to elucidate the pathogenic mechanisms involved in neurodegeneration in AIDS patients with cognitive deficits, the possible effect of HIV-1 transmembrane envelope protein gp41 on expression of the membrane inhibitor of complement mediated cytolysis (CD59) was assessed in human neuronal (SK-N-SH) and astroglial (T98G) cell lines. Western blotting analyses demonstrated that an immunodominant (ID, aa 598-613) gp41 peptide as well as the recombinant gp41 protein encompassing this domain markedly reduced CD59 level in a dose dependent manner whereas p24 and control peptide had little effect. RT-PCR showed that ID peptide also elicited a reduction in the expressed CD59 mRNA level. This gp41 peptide apparently down-regulated phorbol 12,13-dibutyrate induced elevation of CD59 at the protein and mRNA levels in a manner similar to that conferred by protein kinase C inhibitor, H-7 or staurosporine in SK-N-SH. Interestingly, proinflammatory cytokines such as IL-1beta or IFN-gamma as well as LPS greatly decreased CD59 in SK-N-SH and to a lesser extent in T98G whereas TNF-alpha did not significantly alter it. In contrast, antioxidants and anti-inflammatory agents enhanced CD59 expression reversing gp41 peptide mediated inhibitory effect in SK-N-SH. Our data suggest that high level of gp41 or its metabolites as well as impaired protein kinase response, chronic inflammation or antioxidant depletion within HIV-1 infected brains may be associated with a diminished expression of CD59 which would render neuronal cells to susceptible to indirect bystander lysis in the presence of autologous complement.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Adult T cell leukemia/lymphoma with lymphopenia in a Korean.

We experienced a case of adult T cell leukemia/lymphoma (ATLL) in a 48-year-old Korean female, who has never been abroad since birth and no history of blood transfusion. The patient had hypercalcemia and multiple lymphadenopathy. Histopathologic study of left cervical lymph node (LN) and bone marrow (BM) revealed that infiltrates of malignant lymphoid cells were composed of small, medium and large cells with pleomorphic nuclei. Smears of peripheral blood (PB) showed lymphopenia (16%) with the appearance of a few atypical lymphoid cells (less than 2%), but not the typical clover leaf cells seen in ATLL. Immunophenotypic study of LN and BM revealed T cell phenotype. PB showed increased CD4+ T cell (T(H), CD3/CD4+, 57%) and decreased CD8+ T cell counts (T(S), CD3/CD8+, 6.7%). The sera of the patient and her family were reactive for HTLV-I antibody. The specific sequences of pol, env, and tax of HTLV-I DNA were detected in the lymphoma cells and peripheral blood mononuclear cells (PBMC) using polymerase chain reaction. Ultrastructural examination of PBMC confirmed numerous type c virus particles in extracellular space. This case was an acute type of ATLL without overt leukemic features in PB. Despite chemotherapy and intensive conservative treatment, she died 3 months after admission.

Biopsy↗