The bone marrow biopsy is an integral part of the staging process in patients with malignant lymphomas. Bone marrow(BM) involvement indicates stage IV disease, but there are always a lot of cases in which clear separation is not possible when based on morphology alone. Additional difficulties are caused by morphologic discordance between the BM and the primary lymphoma. Immunohistochemical stain, mRNA in situ hybridization (ISH) for light chain restriction and polymerase chain reaction (PCR) for IgH CDR3 and TCRgamma were performed to find a minimal lesion and the clonality in formalin fixed paraffin embedded tissues of 39 primary lymphomas and corresponding BM biopsy specimens. As a result, nine morphologically negative bone marrows of 18 lymphomas were positive by PCR (Group I). Among the 6 lymphoma cases with morphologically suspicious BM involvement (Group II), one was confirmed to be positive for marrow involvement by both mRNA ISH and PCR and the other four by PCR alone. The positive bone marrows of Group I and II revealed gene rearrangement at the same site as the primary lesion, suggesting the same clonality. Thirteen of 15 lymphomas with morphologically positive BM (Group III) had the same clonality in the primary lymphomas and the BM lesion. Three cases among the Group III with morphologic discordance also revealed the same clonality by PCR. This study shows that a combination of mRNA ISH and PCR in addition to an immunohistochemical stain improves the diagnostic sensitivity in the detection of BM involvement and identification of clonality. Among the three different methods used, PCR is the most sensitive in detecting a minimal lesion.
Biopsy ; Bone Marrow ; Formaldehyde ; Gene Rearrangement ; Humans ; In Situ Hybridization ; Lymphoma* ; Paraffin ; Polymerase Chain Reaction ; RNA, Messenger

Recently, p53, c-erbB-2 and nm23 proteins have been studied in breast cancer. The expression of p53 protein indicates the mutation of p53 gene known as a tumor supressor gene, and c-erbB-2 gene amplification has been considered an indicator of poor prognosis and nm23 a metastsis suppressor gene. In order to elucidate the roles and relations of these proteins in the develpoment, progression and metastasis in breast cancer, we studied 89 cases of invasive breast cancer and 32 cases of lymph node metastasis for the expression of p53, c-erbB-2 and nm23 proteins using an immunohistochemical method. The results were as follows: 1) The expression rates of p53, c-erbB-2, and nm23 proteins in breast cancer were 40.4%, 34.8% and 55.1%, respectively. Co-expression of p53 protein and c-erbB-2 protein was found in 20.2% of cases, showing the highest incidence in poorly differentiated type (40%). 2) p53 protein expression was increased in poorly differentiated type but was not statistically significant. On the other hand, the expression of nm23 protein was decreased in poorly differentiated type, which was statistically significant (p<0.05). 3) The correlation of p53 protein expression with c-erbB-2 protein expression was statistically significant (p<0.05) but that with nm23 protein was not. 4) In the cases with lymph node metastasis, discordant expression of p53, c-erbB-2 and nm23 proteins between primary tumor and the lymph node metastatic tumor was found in 9.4%, 3.1% and 18.8% of cases, respectively. The above results suggest that overexpression of p53 and c-erbB-2 proteins and downregulation of nm23 protein are associated with the tumor progression in the breast cancer.
Breast Neoplasms* ; Breast* ; Down-Regulation ; Genes, erbB-2 ; Genes, p53 ; Genes, Suppressor ; Hand ; Incidence ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis ; Receptor, erbB-2

PURPOSE: To determine the effect of genistein, an inhibitor of protein tyrosine kinase, on preretinal neovascularization through the quantification of retinal neovascularization using image analyzer in an experimental rat model. METHODS: In 36 eyes of 36 rats, retinal vein occlusion was induced by photodynamic therapy with an argon green laser and systemic injection of rose bengal (40 mg/kg). The development and progression of retinal neovascularization was followed weekly by fluorescein angiography. Seven rats were sacrificed each week, after which two eyes were prepared with H and E staining for histologic examination, and five were prepared as a control group using ADPase staining for neovascularization analysis. In the remaining fifteen eyes, retinal vein occlusion was also induced using the same method. Immediately after vein occlusion, 4.0 mg of genistein dissolved in dimethyl sulfoxide (DMSO) was injected intraperitoneally twice a day for the first 7 days. Five rats were sacrificed each week and stained with ADPase. After ADPase staining, those samples with evidence of neovascularization were quantified using an image analyzer. RESULTS: No retinal neovasularizaion was found at the end of the first week. The size of retinal neovascularization for the five eyes sacrificed at the end of week 2 and 3 were 6.53+/-2.11 mm2 and 3.77+/-3.51 mm2 in the control group, and 2.22+/-1.01 mm2 and 1.64+/-0.88 mm2 in the genistein treatment group, respectively. Retinal neovascularization was successfully suppressed until two weeks after laser treatment by genistein in this rat neovascularization model. CONCLUSIONS: Genistein may be a useful treatment modality to suppress retinal neovascularization complicated with retinal ischemic injury.
Animals ; Apyrase ; Argon ; Dimethyl Sulfoxide ; Fluorescein Angiography ; Genistein* ; Models, Animal ; Photochemotherapy ; Protein-Tyrosine Kinases ; Rats* ; Retinal Neovascularization ; Retinal Vein Occlusion ; Retinaldehyde ; Rose Bengal ; Thrombosis* ; Veins

BACKGROUND/OBJECTIVES: Inflammatory Bowel Disease (IBD) has rapidly escalated in Asia (including Korea) due to increasing westernized diet patterns subsequent to industrialization. Factors associated with endoplasmic reticulum (ER) stress are demonstrated to be one of the major causes of IBD. This study was conducted to investigate the effect of Lycium barbarum (L. barbarum) on ER stress. MATERIALS/METHODS: Mouse embryonic fibroblast (MEF) cell line and polarized Caco-2 human intestinal epithelial cells were treated with crude extract of the L. chinense fruit (LF). Paracellular permeability was measured to examine the effect of tight junction (TJ) integrity. The regulatory pathways of ER stress were evaluated in MEF knockout (KO) cell lines by qPCR for interleukin (IL) 6, IL8 and XBP1 spliced form (XBP1s). Immunoglobulin binding protein (BiP), XBP1s and CCAAT/enhancer-binding homologous protein (CHOP) expressions were measured by RT-PCR. Scanning Ion Conductance Microscopy (SICM) at high resolution was applied to observe morphological changes after treatments. RESULTS: Exposure to LF extract strengthened the TJ, both in the presence and absence of inflammation. In polarized Caco-2 pretreated with LF, induction in the expression of proinflammatory marker IL8 was not significant, whereas ER stress marker XBP1s expression was significantly increased. In wild type (wt) MEF cells, IL6, CHOP and XBP1 spliced form were dose-dependently induced when exposed to 12.5–50 µg/mL extract. However, absence of XBP1 or IRE1α in MEF cells abolished this effect. CONCLUSION: Results of this study show that LF treatment enhances the barrier function and reduces inflammation and ER stress in an IRE1α-XBP1-dependent manner. These results suggest the preventive effect of LF on healthy intestine, and the possibility of reducing the degree of inflammatory symptoms in IBD patients.
Animals ; Asia ; Carrier Proteins ; Cell Line ; Diet ; Endoplasmic Reticulum ; Epithelial Cells ; Fibroblasts ; Fruit ; Humans ; Immunoglobulins ; Inflammation ; Inflammatory Bowel Diseases ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Intestines ; Lycium ; Mice ; Microscopy ; Permeability ; Tight Junctions

Proteinuria is associated with poor allograft and patient survival in kidney transplant recipients. However, the clinical relevance of spot urine protein-to-creatinine ratio (PCR) or albumin-to-creatinine ratio (ACR) as predictors of renal outcomes during the early postoperative period following kidney transplantation (KT) has not been determined. Methods: This single-center retrospective cohort study included 353 kidney transplant recipients who underwent KT between 2014 and 2017 and were followed up for more than 3 years. Among them, 186 and 167 recipients underwent living donor KT and deceased donor KT, respectively. The PCR and ACR were measured during the immediate postoperative period (within 7 days postoperatively), before discharge (2–3 weeks postoperatively), and 3–6 months postoperatively. Results: The median age of the patients was 51 years (interquartile range, 43–59 years), and 62.9% were male. An immediate postoperative PCR of ≥1 mg/mg was associated with old age, diabetes mellitus, high systolic blood pressure, delayed graft function, and donor factors (deceased donor KT, old age, and high serum creatinine concentrations). The PCR and ACR 3 to 6 months posttransplant were inversely associated with the estimated glomerular filtration rate at 1 year posttransplant. Deceased donor KT recipients with immediate postoperative PCR of ≥3 mg/mg showed a greater incidence of delayed graft function and lower estimated glomerular filtration rate before discharge than those with immediate postoperative PCR of <3 mg/mg. Conclusion: Early postoperative proteinuria is a useful biomarker to predict early renal outcomes after KT.