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Biomedical subjects

D G Lee

Publications and source records attributed to D G Lee.

At least 37 records · Page 2Linked to original sources
PubMed2000

Selective involvement of reactive oxygen intermediates in platelet-activating factor-mediated activation of NF-kappaB.

Although it has been suggested that some biological activities of platelet-activating factor (PAF) are mediated by, at least in part, reactive oxygen intermediates (ROI), the precise mechanisms underlying the interaction between the two remains to be elucidated. Antioxidants, such as alpha-tocopherol acid succinate, N-acetyl-L-Cysteine, pyrrolidinedithiocarbamate failed to inhibit PAF-induced immediate systemic reactions such as lethality, symptoms of disseminated intravascular coagulation, and histological changes such as pulmonary edema and hemorrhage in renal medullae 10 min following PAF injection. In contrast. antioxidants significantly inhibited both the in vivo and in vitro PAF-induced NF-kappaB activation and NF-kappaB-dependent TNF-alpha expression. The effects of the antioxidants were due to their inhibition of PAF-induced degradation of IkappaBalpha, a protein responsible for keeping NF-kappaB in an inactive form. A protein tyrosine kinase and N-tosyl-L-phenylalanine chloromethyl ketone sensitive serine protease were involved in both PAF- and H2O2-induced NF-kappaB activation. Collectively, these data indicate that the PAF-induced NF-kappaB activation is selectively mediated through the generation of ROI.

Acetylcysteine↗
PubMed2000

Pale bodies in hepatocellular carcinoma.

Histochemical, immunohistochemical and ultrastructural studies were performed on cases of hepatocellular carcinoma (HCC) with pale bodies (PB). HCC containing PBs was observed in 3 (5.5%) of 55 consecutively resected HCC cases. Histologically, a large number of hepatocytes displayed pale or eosinophilic staining of the cytoplasm, resulting in ground-glass appearance. They were aggregated in nodular pattern, or diffusely intermixed with other malignant hepatocytes. PBs were negative for periodic-acid Schiff and Masson's trichrome staining. The inclusions showed a strong positive reaction for fibrinogen and some of them were weakly positive for albumin but negative for hepatitis B surface antigen, hepatitis B core antigen, alpha-fetoprotein and alpha-1-antitrypsin. Ultrastructurally, PBs were membrane-bound and contained granular materials of moderate electron density, and were closely related to dilated rough endoplasmic reticulum. These findings support that PBs are secretory fibrinogen accumulated in cystic ER and that such intracellular accumulation possibly reflects a defective transport of fibrinogen.

Albumins↗
PubMed2000

Early ultrastructural changes of apoptosis induced by fumonisin B1 in rat liver.

A time sequential study was performed to investigate the histological and ultrastructural findings of fumonisin B1-induced apoptosis in the male Sprague-Dawley rat liver. Six hours after administration of FB1, marked morphologic changes of hepatocytes included the appearance of small vacuoles along the margin of cell membrane. Twelve hours after injection of FB1, acidophilic degeneration of cells occurred, but no fragmented nucleus was evident around the centrilobular area, with few apoptotic cells. By electron microscope, the degenerated acidophilic cells revealed following changes: characteristic formation of cytoplasmic vacuoles, condensed cytoplasm, detachment from neighboring cells, and as well as margination of nuclear chromatin and swollen mitochondria with amorphous matrical deposit. The number of apoptotic cells or bodies was further enhanced at 24 hours in the vicinity of dense acidophilic cells, resulting in a marked increase over the values of control rats. Serum analysis revealed the elevation of cholesterol levels from the beginning to the end of this experiment. Morphologic data and serum findings in this study support the theory that FB1-induced alteration of membrane lipid constituents of the hepatocytes are likely to be early key events in explaining the FB1 apoptotic effect.

Animals↗
PubMed2000

Necrotizing enterocolitis: experience of 27 cases from a single Korean institution.

Necrotizing enterocolitis (NEC) can involve any site in the gastrointestinal tract and is a fatal complication of immunosuppression. To characterize NEC, clinical and radiological characteristics were analyzed. A total of 27 cases of NEC were identified from January 1993 to August 1998, and medical records were reviewed. NEC was diagnosed by clinical and radiological criteria, and other mimicking conditions were excluded. Of the NEC cases, 22 (81.5%) occurred in patients with underlying hematologic malignancy. All patients complained of abdominal pain and fever at the time of inclusion. Escherichia coli was the most common pathogen identified. The most common finding by computed tomography was single-layered diffuse bowel wall thickening with variable density. Other findings were ascites, fascial thickening, pneumatosis, and mesenteric lymphadenopathy. Of the patients, 25 were treated with antimicrobials with or without recombinant hematopoietic growth factors, and 2 were treated with surgery because of perforation and profound bleeding. Among the 12 patients who died, NEC was the direct cause of death in 7 patients. In conclusion, computed tomography is an effective tool for early diagnosis of NEC. Bowel rest, broad-spectrum antimicrobials, and recombinant hematopoietic growth factors are important aspects of treatment. Surgery should be reserved for complicated cases.

Adolescent↗
PubMed1999

Increase of NAD glycohydrolase activity in uterine cervix cancers is caused by infiltration of lymphocytes.

CD38 is a type II transmembrane glycoprotein which is expressed by hematopoietic and nonhematopoietic cells in human. It has two functions of ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase activities and the sum of these two enzyme activities is identical with NAD glycohydrolase (NADase) activity. The levels of NADase activity in human cervical carcinoma and normal cancer tissue were measured. With a total of 12 patients with cervical cancer and 11 women with normal cervix, cancer tissues were found to have significantly higher NADase and ADP-ribosyl cyclase activities than the control group. Moreover, immunoblot analysis showed an increase of immunoreactivity against CD38 in cervical cancer tissues compared with normal tissues. Immunohistochemical data indicated that the increase of CD38 expression was due to increased infiltration of lymphocytes.

ADP-ribosyl Cyclase↗
PubMed1999

Purification and characterization of a novel chitinase from the entomopathogenic fungus, Metarhizium anisopliae.

A novel chitinase was detected in extracellular culture fluids of the entomopathogenic fungus Metarhizium anisopliae (ATCC 20500) grown in liquid medium containing chitin as a sole carbon source. A chitinase was purified to near homogeneity from culture broth of M. anisopliae by DEAE-Sephacel, CM-Sepharose CL-6B ion-exchange chromatography, and gel filtration with Superose 12HR. The molecular mass of the enzyme determined by SDS-polyacrylamide gel electrophoresis was approximately 60 kDa and the optimum pH of the enzyme was 5.0. This molecular mass is different from values of 33, 43.5, and 45 kDa for endochitinases and 110 kDa for an exochitinase (N-acetylglucosaminidase) from M. anisopliae ME-1 published previously. In addition, N-terminal sequences of 60-kDa chitinase are different from those of 43.4- and 45-kDa endochitinases. The purified enzyme showed high chitinolytic activity against colloidal, crystalline chitin of crab shells as well as against p-nitrophenyl-beta-d-N-acetylglucosamide, p-nitrophenyl-beta-d-N, N'-diacetylchitobiose, and p-nitrophenyl-N, N'-N"-triacetylchitotriose, indicating that this enzyme has both endo- and exochitinase activity.

Chitinases↗
PubMed1998

Isolation and characterization of a chitinase cDNA from the entomopathogenic fungus, Metarhizium anisopliae.

A novel chitinase gene was isolated from Metarhizium anisopliae grown in a medium containing chitin as the sole carbon source. Comparisons of nucleotide sequence of the isolated gene with those of other fungal chitinase genes showed low sequence identity (24.4-36.4%) except for the active site of chitinase. In addition, molecular mass determination of the fused gene product separated on a gel showed that the fused chitinase seems to be about 70 kDa, while the molecular mass calculated from the deduced amino acid sequence can be about 58 kDa. These molecular masses were different from values of 33 kDa for an endochitinase and 110 kDa for an exochitinase (N-acetylglucosaminidase) from M. anisopliae published previously.

Amino Acid Sequence↗
PubMed1998

Chondrolipoma of the nasopharynx.

Lipoma is the commonest soft-tissue tumour arising anywhere in the body, but its occurrence in the nasopharynx is extremely rare. Only four cases in adults have been previously reported in the English literature. We describe a 63-year-old woman with a nasopharyngeal mass that was removed transorally and verified histopathologically as chondrolipoma, that is a lipoma with chondroid metaplasia.

Chondroma↗
PubMed1998

Ovarian sex cord tumor with annular tubules in a patient with Turner syndrome.

A case of ovarian sex cord tumor with annular tubules (SCTAT) in a 24-year old woman with Turner syndrome is presented. Close association of dysgenetic gonads and gonadoblastoma has been clearly documented, and there have been sporadic reports of patients with other gonadal tumors. To our knowledge, a case of SCTAT in a patient with 45,X/46,XX Turner syndrome has not been reported. On the basis of histopathologic, immunohistochemical, and ultrastructural findings, we suggest that the SCTAT originated from pluripotential stem cells of the gonads and differentiated into either granulosa cells or Sertoli cells. We postulate a possible relationship between the SCTAT and gonadoblastoma based on the morphologic resemblance and occurrence in dysgenetic gonads.

Adult↗
PubMed1997

Anti-IL-4 monoclonal antibody prevents antibiotics-induced active fatal anaphylaxis.

We previously reported that anti-IL-4 mAb (11B11) failed to prevent protein-induced fatal murine anaphylaxis. To investigate the effect of anti-IL-4 on hapten-induced anaphylaxis, a model of murine anaphylaxis induced by antibiotics, penicillin V (Pen V) and cephalothin (CET), was developed, and the effect of anti-IL-4 on the anaphylaxis was observed. Pen V and CET induced 100 and 70 to 90% fatal reactions, respectively, when C57BL/6 mice were sensitized i.p. with 500 microg of antibiotic-OVA conjugate with 2 x 10(9) Bordetella pertussis and 1.0 mg of alum and challenged i.v. with 100 microg of antibiotic-BSA conjugate 14 days later. Serum taken from mice sensitized to Pen V passively sensitized normal mice to develop systemic anaphylaxis, and this ability of the serum was abrogated by heating at 56 degrees C for 2 h or depletion of IgE, but not IgG, Abs. Thus, the antibiotic-induced fatal reaction was an IgE-dependent anaphylactic reaction. Administration of anti-IL-4 at the beginning of sensitization completely prevented the fatal anaphylactic reactions to both Pen V and CET. This effect of anti-IL-4 was associated with its suppressive activity on antibiotic-specific serum IgE, but not IgG, levels. More importantly, anti-IL-4 therapy in previously sensitized mice was also effective in preventing the fatal reactions and rapidly reduced the established IgE levels. This study provides a new animal model of hapten-induced anaphylaxis and indicates that blocking of IL-4 activity may be beneficial in allergic diseases caused by a variety of haptens in which IgE Abs play a major role.

Anaphylaxis↗
PubMed1997

Cloning and sequencing of an alpha-glucosidase gene from Aspergillus niger and its expression in A. nidulans.

We have cloned an extracellular alpha-glucosidase gene from Aspergillus niger with oligonucleotide probes synthesized on the basis of the determined peptide sequences. The nucleotide sequence revealed an open reading frame of 985 amino acids split with three introns, and the deduced amino acid sequence was nearly identical to that of the alpha-glucosidase previously determined. The cloned gene was introduced into Aspergillus nidulans, and its expression in the transformants was shown to be regulated by the carbon sources in the medium, suggesting that a common regulatory expression system is shared by these two species as is the case of other starch-degrading enzymes of Aspergillus species.

Amino Acid Sequence↗
PubMed1997

Involvement of nuclear factor-kappa B in platelet-activating factor-mediated tumor necrosis factor-alpha expression.

Tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) are important mediators of inflammatory reactions, and their release is controlled by a positive feedback network. However, the regulatory mechanisms underlying the interaction of these two molecules are unknown. Within 10 min of the injection of lipopolysaccharide (LPS) into C57BL/6 mice, effects inducible by PAF such as anaphylactic shock-like symptoms, disseminated intravascular coagulation, and hemorrhage in renal medullae were observed, and all these pathological changes were prevented by the PAF antagonist, BN 50739. The plasma level of PAF after LPS injection reached a peak at 5 min. TNF-alpha gene expression was evident 20 min after LPS injection and was maximal at 40 min, and the level of serum TNF-alpha reached a peak at 1 h. Pretreatment with BN 50739 inhibited LPS-induced TNF-alpha gene expression and protein synthesis in a dose-dependent manner. Injection of PAF or treatment of the macrophage cell line, J774A.1, with PAF activated the transcription factor, nuclear factor (NF)-kappa B, which is essential for inducible TNF-alpha transcription. The activation of NF-kappa B by PAF preceded the LPS-mediated TNF-alpha gene expression. Pretreatment with BN 50739 inhibited LPS-induced mobilization of NF-kappa B in a dose-dependent manner in vivo as well as in vitro. These data suggest that PAF, which is released immediately or shortly after LPS injection, induces the expression of TNF-alpha through the activation of NF-kappa B.

Animals↗
PubMed1997

Design of novel analogue peptides with potent fungicidal but low hemolytic activity based on the cecropin A-melittin hybrid structure.

In order to design synthetic peptides with potent antifungal activity but low cytotoxic activity under physiological conditions, several analogues of the previously reported cecropin A (CA)-melittin (ME) hybrid peptide, CA(1-8)-ME(1-12), were synthesized. These analogues were designed by analysis of the alpha-helical wheel diagram of CA(1-8)-ME(1-12). Antifungal activities were measured by growth inhibition of the yeast Trichosporon beigelii and by hemolytic assay with human red blood cells, respectively. Substitution of Thr for Lys at position 18 and 19 of CA(1-8)-ME(1-12) caused a dramatic reduction in hemolytic activity. Two analogue peptides (analogue I and III) showed more potent antifungal and lower hemolytic activity than the original peptide. To study the antifungal mechanism of these peptides, fluorescence activated flow cytometry and confocal laser scanning microscopy were performed with the most powerful antifungal analogue I peptide designed in the present study. As determined by propidium iodide staining, fungal cells treated with analogue I or melittin showed higher fluorescence intensity than those treated with the weak antifungal peptide, cecropin A. By confocal microscopy the analogue I was detected in the intracellular region as well as the in cell membrane. These facts suggested that the antifungal function of this novel peptide analogue acts by pore formation in the cell membrane.

Amino Acid Sequence↗
PubMed1997

The use of P31 magnetic resonance spectroscopy to evaluate the effect of ATP-MgCl2 perfusion on the metabolism of rat skin island flaps.

Depleted levels of adenosine triphosphate (ATP) are described as one of the important causes of skin flap failure. This study evaluated the beneficial effects of intra-arterial perfusion of ATP-magnesium chloride (MgCl2) in ischemic neurovascular skin island flaps in the rat and observed the changes of the highenergy phosphate metabolite using phosphorus 31-(P31) magnetic resonance spectroscopy (MRS). The changes of ATP, phosphocreatine (PCr), and inorganic phosphate (Pi) were observed from P31 MRS and the ratios of each metabolite were compared. The extent of skin flap survival was assessed 7 days after operation using an image analyzer. The PCr/Pi ratio of the experimental group (ATP-MgCl2) was significantly different from the control group (balanced salt solution; p < 0.05). Furthermore, the infusion of ATP-MgCl2 (40.3%) significantly improved the area of flap survival compared to the control group (14.2%; p < 0.05). The ratios of PCr/Pi PCr/(PCr + Pi) correlated with the extent of flap survival, and correlation coefficients were 0.59 and 0.60, respectively. In conclusion, ATP-MgCl2 improved skin flap survival. We were able to assess the metabolic state of the ATP-MgCl2-perfused skin flap and found that PCr/Pi ratios correlated with flap survival.

Adenosine Triphosphate↗
PubMed1997

Architecture of the yeast origin recognition complex bound to origins of DNA replication.

In many organisms, the replication of DNA requires the binding of a protein called the initiator to DNA sites referred to as origins of replication. Analyses of multiple initiator proteins bound to their cognate origins have provided important insights into the mechanism by which DNA replication is initiated. To extend this level of analysis to the study of eukaryotic chromosomal replication, we have investigated the architecture of the Saccharomyces cerevisiae origin recognition complex (ORC) bound to yeast origins of replication. Determination of DNA residues important for ORC-origin association indicated that ORC interacts preferentially with one strand of the ARS1 origin of replication. DNA binding assays using ORC complexes lacking one of the six subunits demonstrated that the DNA binding domain of ORC requires the coordinate action of five of the six ORC subunits. Protein-DNA cross-linking studies suggested that recognition of origin sequences is mediated primarily by two different groups of ORC subunits that make sequence-specific contacts with two distinct regions of the DNA. Implications of these findings for ORC function and the mechanism of initiation of eukaryotic DNA replication are discussed.

Animals↗
PubMed1995

Immunohistochemical localization of NAD glycohydrolase in human and rabbit tissues.

NAD glycohydrolase (NADase) is present in many organisms from bacteria to mammals. In any given organism, this enzyme is ubiquitous in many tissues. However, its precise localization and its physiological significance have not been defined. We have determined the distribution of NADase in normal human and rabbit tissues by immunoblotting and immunohistochemistry, using a polyclonal antibody raised in goats. Immunoblot analyses revealed that NADase was highly expressed in the heart, lung, stomach, and liver tissues of the rabbit. From immunohistochemical studies of NADase, high concentrations in both human and rabbit tissues were found in hepatocytes and sinusoidal lining cells, sinus histiocytes of the lymph node, spleen and thymus, glomerular capillary endothelial cells of the kidney, cardiac muscle, endothelium of blood vessels, and erythrocytes.

Animals↗
PubMed1995

Occurrence of disseminated intravascular coagulation (DIC) in active systemic anaphylaxis: role of platelet-activating factor.

The possible occurrence of DIC in active systemic anaphylaxis was investigated in mice. Induction of active systemic anaphylaxis resulted in the development of DIC symptoms such as thrombocytopenia, prolongation of prothrombin time, hypofibrinogaemia, and elevated level of fibrinogen/fibrin degradation products. In addition, in histological examinations, massive congestion and cellular infiltration in pulmonary interstitia, and considerable haemorrhage in renal medullae were observed. All these changes were nearly completely prevented by pretreatment with platelet-activating factor (PAF) antagonist (BN 50739). Moreover, the same haematological and morphological changes were produced by a bolus injection of PAF. These data strongly suggest that DIC occurs in active systemic anaphylaxis and PAF plays a pivotal role in the development of DIC in anaphylaxis.

Anaphylaxis↗