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Biomedical subjects

H B Moon

Publications and source records attributed to H B Moon.

At least 19 recordsLinked to original sources

Expression of insulin-like growth factor-II and insulin-like growth factor binding protein-1 in the placental basal plate from pre-eclamptic pregnancies.

OBJECTIVES: To determine whether expressions of insulin-like growth factor-II (IGF-II) and insulin-like growth factor binding protein-1 (IGFBP-1) are altered in pre-eclamptic placenta and to elucidate the possible relationship between their expressions and a mechanism for inadequate trophoblast invasion in pre-eclampsia. METHODS: Placental tissues were obtained at cesarean delivery from five normotensive, nine mild pre-eclamptic and five severe pre-eclamptic women at 33-39 completed weeks of gestation. After total ribonucleic acid was extracted, reverse transcriptase-polymerase chain reaction was performed to determine IGF-II and IGFBP-1 mRNA expression. Product bands were quantitated by scanning densitometry and results were expressed as ratio of cytokines/beta-actin. Western blot analysis was also done to determine IGF-II and IGFBP-1 protein expression. Statistical analysis was determined by Kruskal-Wallis analysis of variance with the Scheffe multiple post-hoc test. RESULTS: The IGF-II mRNA levels of mild and severe pre-eclamptic placenta were significantly lower than that of uncomplicated placenta (P<0.005, P<0.001, respectively), with the level of severe pre-eclamptic placenta being significantly lower than that of mild pre-eclamptic placenta (P<0.05). As for the IGF-II protein expression, a significant decrease was found among the three groups (P<0.001), correlating with the IGF-II mRNA results. However, the mean IGFBP-1 mRNA levels of mild and severe pre-eclamptic placenta were significantly higher than that of uncomplicated placenta (P<0.05, P<0.005, respectively), with the level of severe pre-eclamptic placenta being significantly raised compared with that of mild pre-eclamptic placenta (P<0.05). Finally, a significant increase of IGFBP-1 protein expression was noted among the three groups (P<0.001), correlating with the IGFBP-1 mRNA results. CONCLUSIONS: This study suggests that IGF-II and IGFBP-1 might be associated with the impaired trophoblastic invasion that may lead to pathogenesis of pre-eclampsia.

Actins↗

Interleukin-10 up-regulates tumour-necrosis-factor-alpha-related apoptosis-inducing ligand (TRAIL) gene expression in mammary epithelial cells at the involution stage.

Although interleukin-10 (IL-10) is known to contribute to inflammation and pathogenesis in mammalian organs, little is known about its precise role in the mammary gland. We found that IL-10 levels fluctuated during the mouse mammary cycle, showing little expression at the lactation stage and the highest expression at the involution stage. To reveal the effects of IL-10 on involution, expression profiles of apoptosis-related genes were examined in mice transgenic for IL-10 as well as in IL-10(-/-) mice. Mild inflammatory lesions by lymphocytes were observed in the mammary glands from four of seven transgenic lines at the lactation stage. It was striking that the expression of tumour-necrosis-factor-alpha-related apoptosis-inducing ligand (TRAIL) among the apoptosis-related genes was elevated approx. 7-fold in the transgenic mice, whereas others were almost unchanged. Furthermore, TRAIL was down-regulated 4-fold in the IL-10(-/-) mice at the involution stage. Elevated expression of TRAIL and of death receptor 4 (DR4) protein was identified at the involution stage of normal mammary glands as well as at the lactation stage of the IL-10 transgenic mice. These results indicate that the elevated expression of IL-10 at the involution stage recruits lymphocytes and induces the expression of TRAIL and DR4. These phenomena might partly contribute to apoptosis in the mammary epithelial cells for entering involution.

Animals↗

Overexpression of membrane-type matrix metalloproteinase-1 gene induces mammary gland abnormalities and adenocarcinoma in transgenic mice.

To investigate the role of membrane-type matrix metalloproteinase-1 (MT1-MMP) in mammary gland development and tumorigenesis, transgenic mice overexpressing MT1-MMP in mammary gland under the control of the mouse mammary tumor virus long terminal repeat-promoter were generated. The mouse mammary tumor virus/MT1-MMP transgenic mice displayed abnormalities in 82% of female mammary glands. The abnormalities were verified as lymphocytic infiltration, fibrosis, hyperplasia, alveolar structure disruption, dysplasia, and adenocarcinoma. Northern and reverse transcription-PCR analyses demonstrated that MT1-MMP mRNA was overexpressed in mammary glands exhibiting abnormalities. Western blot analysis and immunohistochemical studies have revealed that the protein expression level was also increased in these glands. In addition, the beta-casein gene as a functional epithelial cell marker was poorly expressed in the mammary glands of transgenic mice exhibiting abnormalities. Gelatin zymography showed significantly increased MMP-2 activation in these mammary glands. These results showed that overexpression of MT1-MMP induced remodeling of the extracellular matrix and tumor formation in the mammary glands of transgenic mice. Therefore, we suggest that overexpression of MT1-MMP may play a key role in development and tumorigenesis in mammary glands.

Adenocarcinoma↗

Serum ferritin as a serologic marker of activity in systemic lupus erythematosus.

To investigate the relationship between serum ferritin and disease activity in systemic lupus erythematosus (SLE), we enrolled 128 patients with SLE (18 males and 110 females). Twenty-eight patients (2 males and 26 females) with rheumatoid arthritis (RA) served as controls. The SLE patients were subdivided into three groups according to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores: groups A (0-5), B (6-9), and C (> or =10). We prospectively evaluated 48 SLE patients before and after treatment. Serum ferritin and anti-dsDNA antibody were measured by radioimmunometric assay. C-reactive protein (CRP) was measured quantitatively by immunonephelometry. Complements 3 and 4 (C3 and C4) were measured by nephelometry. Serum levels of ferritin during the more active stage of SLE (group C) exceeded those of RA patients and patients at less active stages of SLE (groups A and B). There were no significant differences between RA patients and groups A and B. Serum ferritin was elevated especially in serositis and hematologic manifestation. In this prospective study, changes in SLEDAI scores before and after treatment correlated significantly with serum ferritin levels and inversely to C3 and C4 levels. We confirm that serum ferritin levels can be a useful marker of disease activity in SLE patients.

Adult↗

Lack of relationship between vitamin D receptor polymorphism and bone erosion in rheumatoid arthritis.

We performed this study to investigate the possible association between vitamin D receptor (VDR) gene polymorphism and the focal bone erosion in rheumatoid arthritis (RA) patients in Korea. One hundred and fifty-seven RA patients were enrolled and two control groups were selected. The focal bone erosion score was assessed by modified Sharp's method. Genotyping of VDR polymorphisms was performed by polymerase chain reaction and restriction fragment length polymorphism analysis using two restriction enzyme Taq I and Bsm I. Notably, the distribution of VDR genotype in Korean population was different from Caucasians. The frequencies of "tt" and "BB" genotypes were very rare both in RA patients and in control groups. The frequency distribution of the Taq I and Bsm I genotype was not different between RA patients (TT, 93.6%; Tt, 6.4%; tt, 0%; BB, 0.6%; Bb, 5.1%; bb, 94.3%) and control groups (TT, 90.8%; Tt, 7.5%; tt, 1.7%; BB, 1.4%; Bb, 8.1%; bb, 90.5%). There was no significant difference in the focal bone erosion score (mean +/- SD) according to the VDR genotypes of RA patients (TT, 0.92 +/- 1.79; Tt, 0.4 +/- 0.79; Bb, 0.43 +/- 0.80; bb, 0.92 +/- 1.79; p > 0.05). In conclusion, these results suggest that VDR gene polymorphisms are not associated with the focal bone erosion in RA patients in Korea.

Adolescent↗

Retroperitoneal fibrosis with duodenal stenosis.

Retroperitoneal fibrosis is a rare disease characterized by the formation of dense plaque of fibrous tissue covering the retroperitoneal structures. This disease is commonly presented as ureteral obstruction, but the involvement of duodenum is rare. We report a case of retroperitoneal fibrosis which was complicated with duodenal stenosis and was successfully treated with corticosteroids. A 58-yr-old man, who had history of aorto-iliac bypass graft due to arteriosclerosis obliterans with infrarenal aortic occlusion was admitted to the hospital with abdominal pain and a mass. Abdominal CT scan revealed the periaortic soft tissue mass encircling grafted aorta and stenosis of duodenal third portion. Retroperitoneal fibrosis with duodenal stenosis was diagnosed and prednisolone therapy was initiated. Follow-up CT scan showed that the patient responded to prednisolone therapy with eased pain, shrinking periaortic mass, and reduced duodenal stenosis.

Anti-Inflammatory Agents↗

Nuclear matrix of calreticulin in hepatocellular carcinoma.

Nuclear matrix protein profiles of malignant cells vary from their normal counterparts. By two-dimensional gel electrophoresis, we analyzed nuclear matrix proteins in 11 hepatocellular carcinomas and compared them with corresponding non-neoplastic liver tissue. Although the compositions were mostly similar, several peptides were noted predominantly in the former. The most prominent one was an acidic protein of apparent Mr 62,000, which was identified to be calreticulin upon NH2-terminal amino acid sequencing. By immunoblotting, calreticulin was confirmed to be present abundantly in the nuclear matrix fraction of carcinomas but not in that of the nonmalignant liver tissue. Interestingly, the total content of calreticulin was similar between them. By immunofluorescence microscopy, evident nuclear immunostaining was detected in carcinomas. Calreticulin was also found to be in the nuclear matrices of various carcinoma cell lines. We conclude that calreticulin is a component of the nuclear matrix. The formation and/or expansion of the calreticulin-nuclear matrix may be related to the activated cell growth.

Adult↗

Hydrocortisone enhances allergen-specific IgE production by peripheral blood mononuclear cells from atopic patients with high serum allergen-specific IgE levels.

BACKGROUND: Although there is convincing evidence that human B cells can be induced to produce IgE by a combination of interleukin 4 (IL-4) and hydrocortisone (HC) in atopic subjects, it is still uncertain if this performs the same functions in allergen-specific IgE synthesis. OBJECTIVE: This study was designed to investigate the differences of IgE regulation between atopics and nonatopics, interactions of HC with IL-4, and the correlation between in vitro total IgE, allergen-specific IgE synthesis and serum IgE levels. METHODS: Peripheral blood mononuclear cells (PBMCs) from 16 atopic asthma patients sensitive to Dermatophagoides farinae and seven nonatopic controls were cultured with IL-4 and/or HC. Total IgE and D. farinae-specific IgE in culture supernatant were measured by ELISA and FAST. RESULTS: IL-4 increased total IgE synthesis in PBMCs from both atopics and nonatopics, whereas, HC had this effect only in some atopics who showed spontaneous IgE production in vitro. HC acted synergistically with IL-4 in total IgE synthesis. Their effects were more remarkable in cases with lower total serum IgE levels. PBMCs from eight of 16 atopics produced D. farinae-specific IgE in vitro either spontaneously or by IL-4 and/or HC. HC had more profound effects than IL-4 in these patients. They also showed higher total IgE synthesis by HC, and higher specific serum IgE levels than the others. IL-4 and/or HC did not induce any D. farinae-specific IgE synthesis by PBMCs from nonatopics. CONCLUSION: HC had a more profound effect than IL-4 on the induction of D. farinae-specific IgE synthesis in atopic patients with high serum allergen specific IgE levels. Further studies to determine the causes of these effects, such as the presence of long lived allergen specific B cells as the result of the priming effect of IL-4 in vivo, may be needed.

Adolescent↗

Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein.

BACKGROUND/AIMS: Chronic infection with hepatitis B virus is a high-risk factor for hepatocellular carcinoma in humans. The HBV X-protein, a multi-functional viral regulator, has been suspected to play a positive role in hepatocarcinogenesis, as demonstrated by the high incidence of hepatocellular carcinoma in HBx-expressing transgenic mice, although it is still controversial. The aim of this study was to generate transgenic mice expressing the HBV X-gene under authentic promoter control and to test whether the gene products can cause hepatic tumors. METHODS: Three transgenic mouse lines were generated by microinjecting the X-gene construct into hybrid (C57BL/6 x DBA) eggs. Gene expression was tested by protein and mRNA analyses. During an observation period of 18 months, mice were sacrificed and organs subjected to histologic examinations. RESULTS: Grossly defined hepatocellular carcinomas reproducibly were observed in mice expressing the X-protein, which were investigated through six generations from the age of 11 to 18 months. Among 14 transgenic mice investigated from the age of 11 to 18 months, 12 were found to have hepatocellular carcinoma, grossly or microscopically. The lesion of the hepatocellular carcinoma disclosed a significant increase in the proliferating cell nuclear antigen in the nuclei. CONCLUSION: The incidence of hepatocellular carcinoma (86%) in our HBV X transgenic mice may be highly significant, since, except for one case, HBV X-gene transgenic mice produced in other laboratories did not develop liver tumor or any other pathologic phenomena.

Animals↗

Analysis of stress in the periodontium of the maxillary first molar with a three-dimensional finite element model.

The aim of this study was to simulate the stress response in the periodontium of the maxillary first molar to different moment to force ratios, and to determine the moment to force ratio for translational movement of the tooth by means of the finite element method. The three-dimensional finite element model of the maxillary first molar consisted of 3097 nodes and 2521 isoparametric eight-node solid elements. The model was designed to dissect the periodontal ligament, root, and alveolar bone separately. The results demonstrate the sensitivity of the periodontium to load changes. The stress pattern in the periodontal ligament for a distalizing force without counterbalancing moments showed high concentration at the cervical level of the distobuccal root due to tipping and rotation of the tooth. After various counterrotation as well as countertipping moments were applied, an even distribution of low compression on the distal side of the periodontal ligament was obtained at a countertipping moment to force ratio of 9:1 and a counterrotation moment to force ratio of 5:1. This lower and uniform stress in the periodontal ligament implies that a translational tooth movement may be achieved. Furthermore, high stress concentration was observed on the root surface at the furcation level in contrast with anterior teeth reported to display high concentration at the apex. This result may suggest that the root morphology of the maxillary first molar makes it less susceptible to apical root resorption relative to anterior teeth during tooth movement. The stress patterns in the periodontal ligament corresponded with the load types; those on the root appeared to be highly affected by bending and the high stiffness of the root.

Alveolar Process↗

Growth retardation of inner cell mass cells in polyspermic porcine embryos produced in vitro.

The in vitro viability of polyspermic pig eggs was investigated. Immature oocytes were matured and fertilized in vitro. Approximately 10 h after insemination, the eggs were centrifuged at 12 000 x g for 10 min and individually classified into two (2PN)- and poly-pronuclear (PPN, 3 or 4 pronuclei) eggs. The classified eggs were cultured in vitro or in vivo. Nuclei numbers of inner cell mass (ICM) and trophectoderm (TE) were compared between 2PN- and PPN-derived blastocysts. The frequency of development in vitro of 2PN and PPN eggs to the blastocyst stage was 53.6% and 40.7%, respectively. The mean number (8.2 +/- 0.7, n = 48) of ICM nuclei of 2PN-derived blastocysts was higher than that (4.2 +/- 0.8, n = 37) of PPN-derived blastocysts (p < 0.001), whereas there was no difference (p > 0.05) in mean numbers of total (46.7 +/- 3.4 vs. 39. 9 +/- 3.9) and TE nuclei (38.5 +/- 2.9 vs. 35.7 +/- 3.3) between the two groups. Development of 2PN and PPN eggs cultured in vivo to the blastocyst stage was 33.3% and 27.4%, respectively. The numbers of ICM and TE nuclei of these embryos cultured in vivo showed a pattern similar to that for the in vitro-produced blastocysts. Additionally, fetuses were obtained on Day 21 from both the 2PN and the PPN groups. This suggests that polyspermic pig embryos develop to the blastocyst stage and beyond, although showing a smaller ICM cell number as compared to normal embryos.

Animals↗

Matrix attachment region sequences enhanced the expression frequency of a whey acidic protein/human lactoferrin fusion gene in the mammary gland of transgenic mice.

To elevate the expression frequency of transgenes in transgenic mice, the chicken lysozyme matrix attachment region (MAR) sequence was used by combining it with a transgene. The whey acidic protein (WAP) promoter/human lactoferrin (hLF) cDNA fusion transgene (pWL) was connected to the chicken lysozyme MAR sequence at its 5'-end (pMWL). While only two of three mice became transgenic from the pWL vector expressed hLF, all seven mice from the pMWL vector expressed the transgene in their lactating mammary glands. To evaluate the effect of lactogenic hormones on transgene expression, experiments with the primary culture of transgenic mammary explants were performed. It was revealed that the expression of transgenes was slightly increased by insulin plus dexamethasone or insulin plus prolactin treatment. However it was not increased by insulin, dexamethasone or prolactin (IDP) treatment alone. In contrast, the endogenous WAP gene was expressed only in the IDP treated group. These results demonstrate that MAR sequences are effective in improving the expression frequency of transgenes in transgenic mice although the developmental and hormonal regulations are not the same as those of the endogenous WAP gene.

Animals↗

Lipocortin 1 binding sites on human T-cells: the population of cells with the binding sites is larger in CD8+ T-lymphocytes than in CD4+ T-lymphocytes.

Lipocortin 1 (LC1) is believed to be a mediator of glucocorticoids in displaying anti-inflammatory and immune suppressive responses. The existence of specific LC1 binding sites (putative receptor) on monocytes and neutrophils has been reported. We have studied the distribution of LC1 binding sites in human peripheral blood leukocytes by flow cytometry. The population of cells with LC1 binding sites was much larger in monocytes than in lymphocytes in both rheumatoid arthritis patients (93.1 +/- 2.3% vs 8.8 +/- 1.0%) and healthy volunteers (97.0 +/- 0.9% vs 9.9 +/- 1.5%). The LC1 binding cell population was larger in CD8+ T-lymphocytes than in CD4+ T-lymphocytes in both healthy volunteers (26.4 +/- 4.5% vs 10.6 +/- 2.0%) and rheumatoid arthritis patients (28.8 +/- 4.7% vs 8.7 +/- 2.1%). No difference in LC1 binding cell populations was found between rheumatoid arthritis patients and healthy controls.

Annexin A1↗

Translocation of lipocortin (annexin) 1 to the membrane of U937 cells induced by phorbol ester, but not by dexamethasone.

1. Induction of lipocortin 1 secretion by dexamethasone has been demonstrated, although the secretory mechanism is still unknown. We have studied the effects of 12-tetradecanoyl phorbol 13-acetate (TPA) and/or dexamethasone on the expression, translocation, and secretion of lipocortin 1 in U937 cells. 2. The expression of lipocortin 1 and its mRNA increased during TPA-induced differentiation of U937 cells to a maximum of 1.9 fold and 8.2 fold, respectively, after 48 h. Both the protein and the mRNA levels decreased after 48 h. 3. TPA caused the translocation of lipocortin 1 from the cytosol to the membrane of U937 cells in a time-dependent manner, as determined by Western blot analysis. The translocation was concurrent with the differentiation of the cells. After 48 h of TPA treatment, 82.6 +/- 6.5% of lipocortin 1 was present in the membrane fraction compared to 41.6 +/- 1.7% in untreated cells. 4. The amount of lipocortin 1 that was externally bound (associated) with the membrane increased to 3.2 fold as the cytosol to membrane translocation of lipocortin 1 increased. 5. Dexamethasone decreased the externally bound lipocortin 1, but had no effect on the cytosol to membrane translocation. 6. This offers a model system with which the function and the secretion mechanism of lipocortin 1 can be studied. Our data is consistent with the hypothesis that the secretory mechanism is through an unknown pathway, involving the translocation of lipocortin 1 from the cytosol to the internal membranes, and then, its secretion to the external membrane.

Animals↗

A case of polyarteritis nodosa with bilateral ureteral obstruction.

We report a case of bilateral ureteral obstruction most likely caused by polyarteritis nodosa. The diagnosis was based upon muscle biopsy which showed typical necrotizing vasculitis in medium size artery in conjunction with microaneurysms in renal angiography. Ureteral obstruction is a rare manifestation of polyarteritis nodosa. This condition is thought to result from vasculitis of periureteral vessels. The patient was managed with prednisolone alone, which resulted in complete resolution of ureteral obstruction on both sides.

Female↗