Proliferative Activity of Pituitary Mammotrophs in Culture : a Morphological Study on DNA Synthesis Using In Vitro Bromodeoxyuridine Labeling Method

The present study was designed to investigate the proliferative activity of mammotroph in the long-term monolayer cultures of male rat pituitaries by use of bromodeoxyuridineflsrdl.ll-labeltnq technique combined with double immunohistochemical staining. Rat anterior pituitary cells were exposed to 100 uM BrdU for 4 hrs at 4, 7, 12, 15, 20, 25 and 30 days in the primary cultures. After fixation with modified Camoy's fixative, double immunohistochemical staining with anti-BrdU and antiprolactin antibody was performed. It was shown that the ratio of BrdU-Iabeled mammotrophs per 100 mammotrophs(BrdU Labeling Index) was 8.2% at 4 day and 8. 0% at 7 day in our cultures. Thereafter, it decreased until 30 days(1.7%). These results demonstrated that the increase in the proportion of mammotrophs observed in our previous monolayer cultures is caused, at least in part, by the cell division of mammortrophs

Ultrastructure of Cryptosporidium parvum Found in the Small Intestine of Immunosuppressed Mice

The ultrastructure of various stages of Cryptosporidium parvum was observed by transmission electron microscopy. C. parvum infection was activated in the small intestine of Korean laboratory mice (fCR) by immunosuppression with prednisolone for 7 weeks. The oocyst discharge was confirmed by modified Kinyon's acid fast stain of fecal specimens. Various endogenous stages of parasites, i. e., trophozoites, meronts, merozoites, and macrogametocytes, were observed in the middle part of the small intestine, as an extracytoplasmic but intracellular parasite of host mucosal epithelial cells. In trophozoites, a large nucleus with a prominent nucleolus was seen, and as they developed into meronts, endoplasmic reticulum appeared prominently in the cytoplasm. Two kinds of meronts, type I and type II, with eight and four merozoites respectively, were found. New merozoites were produced by nuclear division and external budding of the residual body of the meronts. The merozoites were lined with two unit membranes, unlike C. muris that has three membranes, and a nucleus was located near the posterior end. Mature merozoites had conoids, rhoptries and numerous micronemes; the characteristic structures of coccidian parasites. Macrogametocytes were largely vacuolated and "wall-forming body I" was recognized. Other sexual stages were difficult to recognize from our specimens. The present study confirmed that the Cryptosporidium found in the small intestine of Korean laboratory mice has a characteristic ultrastructure consistent with C. parvum

c-Jun N-terminal kinase activation has a prognostic implication and is negatively associated with FOXO1 activation in gastric cancer

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background Since the biological function of c-Jun N-terminal kinase (JNK) in gastric cancer remains unclear, we investigated the clinical significance of JNK activation and its association with FOXO1 activation. Methods Immunohistochemical tissue array analysis of 483 human gastric cancer specimens was performed, and the results of the immunostaining were quantified. The correlation between JNK activation (nuclear staining for pJNK) and clinicopathological features, the proliferation index, prognosis or FOXO1 inactivation (cytoplasmic staining for pFOXO1) was analyzed. The SNU-638 gastric cancer cell line was used for in vitro analysis. Results Nuclear staining of pJNK was found in 38 % of the gastric carcinomas and was higher in the early stages of pTNM (P < 0.001). pJNK staining negatively correlated with lymphatic invasion (P = 0.034) and positively correlated with intestinal type by Laurens classification (P = 0.037), Ki-67-labeling index (P < 0.001), cyclin D1 (P = 0.045), cyclin E (P < 0.001) and pFOXO1 (P < 0.001). JNK activation correlated with a longer patients survival (P =0.008) and patients with a JNK-active and FOXO1-inactive tumor had a higher survival rate than the remainder of the population (P = 0.004). In vitro analysis showed that JNK inhibition by SP600125 in SNU-638 cells decreased cyclin D1 protein expression and increased FOXO1 activation. Further, JNK inhibition markedly suppressed colony formation, which was partially restored by FOXO1 shRNA expression. Conclusions Our results indicate that JNK activation may serve as a valuable prognostic factor in gastric cancer, and that it is implicated in gastric tumorigenesis, at least in part, through FOXO1 inhibition

Constitutive phosphorylation of the FOXO1 transcription factor in gastric cancer cells correlates with microvessel area and the expressions of angiogenesis-related molecules

<p>Abstract</p> <p>Background</p> <p>Although FOXO transcription factors may have an anti-angiogenic role, little is known about their role in tumor angiogenesis. The present study was performed to investigate the correlation between the constitutive expression of phosphorylated FOXO1 (pFOXO1) and angiogenesis in gastric cancer.</p> <p>Methods</p> <p>Immunohistochemistry was performed on tissue array slides containing 272 gastric carcinoma specimens, and the correlations between the cytoplasmic pFOXO1 expression in gastric cancer cells and CD34-immunopositive microvessel area (MVA) or the expressions of angiogenesis-related molecules were analyzed. <it>In vitro </it>analyses with Western blotting and semiquantitative reverse transcription-polymerase chain reaction were performed using the stable SNU-638 gastric cancer cell line transfected with lentivirus-delivered FOXO1 short hairpin RNA.</p> <p>Results</p> <p>The cytoplasmic expression of pFOXO1 in tumor cells was observed in 85% of gastric carcinoma cases, and was found to be positively associated with higher MVA (<it>P </it>= 0.048). Moreover, pFOXO1 expression was positively correlated with the expressions of several angiogenesis-related proteins, including hypoxia inducible factor-1α (HIF-1α, <it>P </it>= 0.003), vessel endothelial growth factor (<it>P </it>= 0.004), phosphorylated protein kinase B (<it>P </it>< 0.001), and nuclear factor-κB (<it>P </it>= 0.040). In contrast, the expression of pFOXO1 was not correlated with that of phosphorylated signal transducer and activator of transcription 3 or β-catenin. In addition, cell culture experiments showed that FOXO1 suppression increased the mRNA and protein expressions of HIF-1α.</p> <p>Conclusion</p> <p>Our results suggest that pFOXO1 expression in cancer cells plays a role in gastric cancer angiogenesis via mechanisms involving various angiogenesis-related molecules. Animal experiments are needed to confirm the anti-angiogenic role of FOXO1 in human gastric cancer.</p

Constitutive activation of glycogen synthase kinase-3β correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer

Background: Aberrant regulation of glycogen synthase kinase-3 beta (GSK-3 beta) has been implicated in several human cancers; however, it has not been reported in the gastric cancer tissues to date. The present study was performed to determine the expression status of active form of GSK-3 beta phosphorylated at Tyr(216) (pGSK-3 beta) and its relationship with other tumor-associated proteins in human gastric cancers. Methods: Immunohistochemistry was performed on tissue array slides containing 281 human gastric carcinoma specimens. In addition, gastric cancer cells were cultured and treated with a GSK-3 beta inhibitor lithium chloride (LiCl) for immunoblot analysis. Results: We found that pGSK-3 beta was expressed in 129 (46%) of 281 cases examined, and was higher in the early-stages of pathologic tumor-node-metastasis (P < 0.001). The expression of pGSK-3 beta inversely correlated with lymphatic invasion (P < 0.001) and lymph node metastasis (P < 0.001) and correlated with a longer patient survival (P < 0.001). In addition, pGSK-3 beta expression positively correlated with that of p16, p21, p27, p53, APC, PTEN, MGMT, SMAD4, or KAl1 (P < 0.05), but not with that of cyclin D1. This was confirmed by immunoblot analysis using SNU-668 gastric cancer cells treated with LiCl. Conclusions: GSK-3 beta activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis. Thus, these findings suggest that GSK-3 beta activation is a useful prognostic marker for the early-stage gastric cancer.Hirakawa H, 2009, ONCOL REP, V22, P481, DOI 10.3892/or_00000460Dar AA, 2009, ONCOGENE, V28, P866, DOI 10.1038/onc.2008.434Holmes T, 2008, STEM CELLS, V26, P1288, DOI 10.1634/stemcells.2007-0600Wang Q, 2008, CELL DEATH DIFFER, V15, P908, DOI 10.1038/cdd.2008.2Takahashi-Yanaga F, 2008, CELL SIGNAL, V20, P581, DOI 10.1016/j.cellsig.2007.10.018Pan MH, 2007, J AGR FOOD CHEM, V55, P7777, DOI 10.1021/jf071520hShakoori A, 2007, CANCER SCI, V98, P1388, DOI 10.1111/j.1349-7006.2007.00545.xZheng HC, 2007, ANTICANCER RES, V27, P3561Saegusa M, 2007, J PATHOL, V213, P35, DOI 10.1002/path.2198Ma C, 2007, CANCER RES, V67, P7756, DOI 10.1158/0008-5472.CAN-06-4665Forde JE, 2007, CELL MOL LIFE SCI, V64, P1930, DOI 10.1007/s00018-007-7045-7Li YW, 2007, J BIOL CHEM, V282, P21542, DOI 10.1074/jbc.M701978200Ding QQ, 2007, CANCER RES, V67, P4564, DOI 10.1158/0008-5472.CAN-06-1788Kunnimalaiyaan M, 2007, MOL CANCER THER, V6, P1151, DOI 10.1158/1535-7163.MCT-06-0665Soto-Cerrato V, 2007, MOL CANCER THER, V6, P362, DOI 10.1158/1535-7163.MCT-06-0266Cao Q, 2006, CELL RES, V16, P671, DOI 10.1038/sj.cr.7310078Yang CH, 2006, PRECIS AGRIC, V7, P33, DOI 10.1007/s11119-005-6788-0Crew KD, 2006, WORLD J GASTROENTERO, V12, P354Mai W, 2007, ONCOLOGY-BASEL, V71, P297, DOI 10.1159/000106429Tan J, 2005, CANCER RES, V65, P9012, DOI 10.1158/0008-5472.CAN-05-1226Shakoori A, 2005, BIOCHEM BIOPH RES CO, V334, P1365, DOI 10.1016/j.bbrc.2005.07.041Farago M, 2005, CANCER RES, V65, P5792Ghosh JC, 2005, CLIN CANCER RES, V11, P4580Liao XB, 2003, MOL CANCER THER, V2, P1215Lee HS, 2003, J PATHOL, V200, P39, DOI 10.1002/path.1288Doble BW, 2003, J CELL SCI, V116, P1175, DOI 10.1242/jcs.00384Gotoh J, 2003, CARCINOGENESIS, V24, P435Goto H, 2002, ORAL ONCOL, V38, P549Lee HS, 2001, INT J CANCER, V91, P619D`Amico M, 2000, J BIOL CHEM, V275, P32649, DOI 10.1074/jbc.M000643200Endoh Y, 2000, J PATHOL, V191, P257Wu LY, 1998, J NATL MED ASSOC, V90, P410WOODGETT JR, 1984, BIOCHIM BIOPHYS ACTA, V788, P339

Integration of decision support systems to improve decision support performance

Decision support system (DSS) is a well-established research and development area. Traditional isolated, stand-alone DSS has been recently facing new challenges. In order to improve the performance of DSS to meet the challenges, research has been actively carried out to develop integrated decision support systems (IDSS). This paper reviews the current research efforts with regard to the development of IDSS. The focus of the paper is on the integration aspect for IDSS through multiple perspectives, and the technologies that support this integration. More than 100 papers and software systems are discussed. Current research efforts and the development status of IDSS are explained, compared and classified. In addition, future trends and challenges in integration are outlined. The paper concludes that by addressing integration, better support will be provided to decision makers, with the expectation of both better decisions and improved decision making processes

Defining the optimal dose of radiation in leukemic patients with extramedullary lesions

<p>Abstract</p> <p>Background</p> <p>Analysis of the clinical response of extramedullary lesions in leukemic patients treated with radiation therapy (RT) and defining the optimal dose of radiation.</p> <p>Methods</p> <p>Forty-two extramedullary lesions found in 24 leukemic patients treated with RT were reviewed. The radiation was delivered usually 2 Gy/day, up to a median of 20 Gy (range: 18.0-40.8). The clinical response and symptom palliation effect were analyzed. The factors affecting the response were also included in the analysis.</p> <p>Results</p> <p>After a median time of 7.9 weeks, the overall response rate was 76.2%. A complete response (CR) was achieved in 35.7%, a partial response in 40.5%. The symptom was relieved in 85.7% sites. The overall response rate was better in patients whose initial tumor size was smaller than 10 cm²(<it>p = 0.010</it>) or who were treated with more than 25 Gy (<it>p = 0.031</it>). The overall CR rate was also higher in those who had smaller tumors (smaller than 6 cm or 30 cm²) (<it>p = 0.015)</it>, or when the tumor was located in soft tissue (<it>p = 0.029</it>).</p> <p>Conclusions</p> <p>Extramedullary lesions in leukemic patients can be successfully treated with RT. The tumor response rate was excellent and symptom relief was achieved in almost all patients. There was a better response to treatment when the tumor was small or it was located in soft tissue. Although, there was no definite correlation between volume reduction and total dose, it seems that higher total dose more of than 25 Gy is needed for better response.</p

탄닌산 처리후의 내이감각세포내 횡문소기관 미세구조의 관찰

Striated organelle (Friedmann body, laminated cytoplasmic inclusion) was first observed in 1963 by Friedmann et al. in the degenerating utricular hair cells from patients with Meniers disease. They reported this Friedmann body, consisting of alternating thick and thin electronopaque lines to form a characteristic pattern, near the surface or within the cytoplasm of degenerating cells. The striated organelles have usually been associated with pathological conditions such as eighth nerve tumors (Hilding and House, 1964) , Conn's syndrome (Friedmann et aI., 1965), drug intoxication (Friedmann et aI., 1966; Jahnke, 1969), or with old age (Rosenhall et aI., 1974). Nevertheless, their consistent occurrence has also been noted in the inner ear hair cells of normal cat (Spoedlin , 1966), squirrel-monkey (Engstrom et aI., 1972), chinchilla (Slepecky et aI., 1980), and rat (Ross and Bourne, 1983). From these reports, striated organelle was proposed to be the normal constituent of hair cells (Slepecky et aI., 1980). Although several possibilities about the role of the striated organelle have been suggested (Slepecky, 1980; Jorgensen, 1982; Ross, 1982), no clear explanation has been achicved. Therefore, it is important to observe more morphological chacteristics of the structure which will become the basis of any functional investigation. In order to obtain the enhanced visibility of the striated organelle, tannic acid which acts as a mordant between osmium treated structure and lead (Simionescu et aI., 1976) was added to glutaraldehyde fixative

Studies on Comparative Cytoarchitectonics: Effects of Aging on Anterior Transverse Temporal Gyral Cortex and Posterior Transverse Temporal Gyral Cortex in Human Brain

The corticies of summit of anterior transverse temporal gyrus (Brodmann's cortical area 41) and of posterior transverse temporal gyrus (Brodrnann's cortical area 42) have been compared in terms of aging effects on the cytoarchitecture of both areas. Samples were taken from 290 hemispheres of 145 normal human brains (85 of male and 60 of female). No statistically significant differences between the cortical thickness and the relative total glial cell density of the two cortical areas were noted. But the relative total neuronal cell density of Brodmann's cortical area 41 was significantly higher than that of area 42. There was no aging effect on the relative total neuronal cell density in both cortical areas. But the relative total glial cell density tended to increase gradually along with the increment of age. The cortical thickness tended to increase gradually until the age 16-20 and thereafter decrease in both cortical areas