Histology and histopathology Vol.29, nº 9 (2014)
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- PublicationOpen AccessIntegrated extracellular matrix signaling in mammary gland development and breast cancer progression(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Zhu, Jieqing; Xiong, Gaofeng; Trinkle, Christine; Xu, RenExtracellular matrix (ECM), a major component of the cellular microenvironment, plays critical roles in normal tissue morphogenesis and disease progression. Binding of ECM to membrane receptor proteins, such as integrin, discoidin domain receptors, and dystroglycan, elicits biochemical and biomechanical signals that control cellular architecture and gene expression. These ECM signals cooperate with growth factors and hormones to regulate cell migration, differentiation, and transformation. ECM signaling is tightly regulated during normal mammary gland development. Deposition and alignment of fibrillar collagens direct migration and invasion of mammary epithelial cells during branching morphogenesis. Basement membrane proteins are required for polarized acinar morphogenesis and milk protein expression. Deregulation of ECM proteins in the long run is sufficient to promote breast cancer development and progression. Recent studies demonstrate that the integrated biophysical and biochemical signals from ECM and soluble factors are crucial for normal mammary gland development as well as breast cancer progression.
- PublicationOpen AccessAnti-apoptotic activity in deep pelvic endometriosis(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Abdalla Ribeiro, Helizabet S.; Galvão, Maria Antonieta Longo; Aoki, Tsutomu; Aldrighi, José Mendes; Ribeiro, Paulo AyrozaSince endometriosis is a proliferative disease we evaluated the presence of anti-apoptotic factor (Bcl2) and pro-apoptotic factor (Bax) in deep pelvic endometriosis. A Cross-sectional observational study was performed at Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil. Forty women aged 26 to 46 years with deep endometriosis were selected. They had not been clinically treated for at least 3 months prior to surgery and then underwent surgical laparoscopy to treat the disease. During the surgery, tissue was collected from the uterosacral ligaments and the rectosigmoid; an endometrial biopsy was also performed as a control. All interventions were performed by the same surgeon. The specimens were sent for pathological and immunohistochemical analyses; endometriosis was confirmed in all patients. After the immunohistochemical reaction a semi-quantitative evaluation of the staining intensity (relative optical density-ROD) was conducted, applying the digital densitometric analysis system. In the uterosacral ligaments 97.5% of the specimens were positive for Bcl2 whereas in the rectosigmoid 100% were positive. In the endometrium we observed that 87.5% were positive for Bcl2. BAX expression was null in the rectosigmoid and in the endometrium. In the uterosacral ligaments 2.5% of the specimens expressed BAX. The relative optical density of Bcl2 was higher in the rectosigmoid and in the uterosacral ligament when compared to the endometrium, 0.141±0.002; 0.129±0.001, respectively (p<0.01). We concluded that the anti-apoptotic factor Bcl-2 was expressed in all studied specimens, but in a higher staining intensity in the rectosigmoid and in the uterossacral ligaments in comparison to the endometrium. The pro-apoptotic factor Bax had virtually no expression in the studied tissues.
- PublicationOpen AccessAmelioration of hypercholesterolemiainduced hepatic changes with red grape juice: A histopathological study(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Al-Ahmadi, Ahlam Abdulaziz; Ali, Soad Shaker; Ayuob, Nasra Naeim; Al Ansary, Abeer KhaledObjectives: Hypercholesterolemia was confirmed as a risk factor for hepatic fibrosis, as well atherosclerosis and coronary heart disease. This biochemical and histoplathological study was conducted to investigate the possible protective effect of red grape against hepatic injury induced by a high-cholesterol diet (HCD). Material and methods: Thirty male Wister rats were randomly divided into three groups (n=10): the control received saline, the induction group was fed HCD, and the treated group was fed a HCD and 0.4 ml of 100% red grape juice (RGJ) for 13 weeks. After the animals were sacrificed, liver tissue samples were taken to be processed for light and electron microscopy examination. Results: The administration of the RGJ and HCD significantly decreased the animals’ blood glucose, insulin, cholesterol, triglycerides, Low Density Lipoprotein levels and increased their High Density Lipoprotein level compared to the rats fed the HCD alone. It also decreased the periportal (macro- and microvesicular) steatosis, fibrosis, lymphocytic infiltration and blood sinusoidal congestion that were observed in HCD-fed rats alone. The RGJ reduced the number of activated myofibrobasts. This was confirmed by a reduction in the expression of alpha smooth muscle actin and desmin. The RGJ increased, although not significantly, the expression of endothelial Nitric Oxide Synthetase. Conclusion: The administration of RGJ succeeded in alleviating the biochemical and, to some extent, the histopathological changes induced by the high cholesterol diet. Consumption of fresh RGJ or its pharmaceutical preparations is advised especially for those who are used to eat a high fat diet.
- PublicationOpen AccessCharacterization of rat testicular teratoma and its derived cell lines, with particular reference to possible mesenchymal differentiations(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Yamate, Jyoji; Gamou, Katsuhiro; Izawa-Ogata, Keiko; Kotera, Takashi; Izawa, Takeshi; Takenaka, Shigeo; Sawamoto, Osamu; Kuwamura, MitsuruThe original tumor, 4 cm in diameter, was found in the left testis of a 2-month old SD rat. The tumor consisted of well-differentiated, mature tissues such as bone, cartilage, adipose tissue, smooth and skeletal muscles, skin, hair, glands (salivary, sebaceous, apocrine and pancreatic exocrine glands) and trachea, as well as nerve tissues. The tumor was diagnosed as a mature type of teratoma, a rare in rat testis. Cloned cell lines (named TSD-B4S and TSD-F9R) were established from the tumor; cellular properties of these cell lines were similar to each other; basically, their cultured cells exhibited vimentin-positive mesenchymal nature with occasional cells reacting to α-smooth muscle actin, glial fibrillary acidic protein and CD163 (a macrophage marker). The cell lines showed tumorigenicity when inoculated into nude mice, being composed of immature mesenchymal cells arranged mainly in a sheet. In TSDB4S cells treated with differentiation factors, we demonstrated mesenchymal differentiations towards adipogenic, osteogenic and myofibrogenic cells. The cell line (TSD-B4S) would become a useful tool for studies on stem cell differentiation, because the teratoma arises from primordial germ cells like embryonic stem cells.
- PublicationOpen AccessHsp27 and its expression pattern in diffusely infiltrating astrocytomas(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Mäkelä, Katri S.; Haapasalo, Joonas A.; Ilvesaro, Joanna M.; Parkkila, Seppo; Paavonen, Timo; Haapasalo, Hannu K.Aims: Heat shock protein 27 (Hsp27) is induced by cell stress conditions. In the presence of oxidative stress it functions as an antioxidant. To study the putative expression patterns and clinical significance of Hsp27, we assessed the associations between Hsp27, R132H mutation of Isocitrate dehydrogenase1 (IDH1- R132H), Hypoxia-inducible factor subunit alpha (HIF-1 alpha), Carbonic anhydrase IX (CA IX), and patient prognosis in astrocytic gliomas. Methods: Tissue micro-array samples of 295 grade II-IV astrocytomas were stained immunohistochemically for Hsp27, IDH1-R132H, HIF-1 alpha, and CA IX. We tested their relationship with clinicopathological features and patient survival. Results: There was a significant correlation between Hsp27 expression and increasing WHO grade (p<0.001). Hsp27 expression correlated significantly with IDH1 mutation when studied within the entire cohort (p<0.001) as well as separately in WHO grade II and III tumors (p=0.006 and 0.002, respectively). IDH1 mutation and HIF-1 alpha positive staining were detected simultaneously (p<0.001). In IDH1 mutated tumors, positive HIF-1 alpha staining correlated with CA IX expression (p=0.027), whereas no such correlation was found in IDH1 non-mutated tumors. IDH1 mutation was associated with a low cell proliferation index (p=0.001) and HIF-1 alpha with increasing proliferation (p=0.003). Hsp27 expression was associated with a shorter rate of patient survival in univariate survival analysis (p=0.001). In multivariate survival analysis, patient age, IDH1 mutation and HIF-1 alpha appeared as independent prognostic factors (p<0.000, <0.000 and 0.011 respectively) Conclusions: Hsp27 expression is associated with increasing WHO grade and patient prognosis in astrocytic gliomas. The results suggest that IDH1 mutation may have an effect on the expression pathways of Hsp27 and CA IX.
- PublicationOpen AccessEffect of endogenous sulfur dioxide in regulating cardiovascular oxidative stress(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Zhu, Mingzhu; Du, Junbao; Liu, Angie Dong; Holmberg, Lukas; Tang, Chaoshu; Jin, HongfangIn the middle of the 1980s, nitric oxide received extensive attention because of its significant effects in life science. Then, carbon monoxide and hydrogen sulfide were discovered to be gasotransmitters playing important roles in regulating cellular homeostasis. As a common air pollutant, sulfur dioxide (SO2) can cause great harm to the human body by producing free radicals, which causes oxidative damage to various organs. Recently, endogenous SO2 was found to be produced in the cardiovascular system and might be a bioactive molecule regulating the physiological activities including cardiovascular oxidative stress.
- PublicationOpen AccessAberrant expressions of delta-protocadherins in the brain of Npc1 mutant mice(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Yan, Xin; Lukas, Jan; Lin, Juntang; Ernst, Mathias; Koczan, Dirk; Witt, Martin; Fuellen, Georg; Wree, Andreas; Rolfs, Arndt; Luo, JiankaiNiemann-Pick type C1 (NPC1) disease is an autosomal recessive disorder characterized by dysmyelination and neurodegeneration, which can result in the death of patients in early childhood in some cases. Members of the delta-protocadherins (Pcdhs) play important roles in neurogenesis and brain development. In this study, we compared expression profiles of Pcdhs in the brain between wild-type and Npc1 mutant mice from postnatal day (P) 9 onwards by in situ hybridization. Our data show that laminar distribution of some Pcdhs in the cerebral cortex of Npc1 mutated mice is different from that of wild-type mice. Furthermore, expressions of Pcdhs by oligodendrocytes in the corpus callosum and by Purkinje cells and granular cells in the cerebellum are strongly decreased in Npc1 mutated mice at later stages. Taken together, our data suggest that aberrant expression of Pcdhs is a pathological process accompanied by neurodegeneration in Npc1 mutant mice.
- PublicationOpen AccessIntrinsic and extrinsic regulation of mammalian hematopoiesis in the fetal liver(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Swain, Anthony; Inoue, Tomoko; Tan, Keai Sinn; Nakanishi, Yoichi; Sugiyama, DaisukeThe fetal liver (FL) is an important structure in expansion and differentiation of hematopoietic stem cells (HSC), but despite this little is known about the exact mechanisms in which FL hematopoiesis takes place. Primitive hematopoiesis gives way to definitive hematopoiesis at 12.5 dpc in mice and the process is regulated by a number of intrinsic and extrinsic factors. Intrinsic regulations are intracellular processes that have been reported to be important in the initiation of definitive hematopoiesis. Several structures are involved with extrinsic regulations of hematopoiesis within the FL, including hepatoblasts and liver sinusoidal endothelial cells (LSEC). Hepatoblasts and endothelial cells comprise separate niches involved in the extrinsic regulation of hematopoiesis. Studies have shown that cocultures with fetal liver stromal cells can promote the expansion of erythroid cells, although the way in which stromal cells do this is still unknown. Understanding the mechanisms in which hematopoiesis is regulated in the FL could lead to the production of novel therapies involving the safe and reliable transplantation of HSCs to patients with blood and bone marrow complications. This review aims to summarize the current state of knowledge about the regulation of hematopoiesis specifically within the FL.
- PublicationOpen AccessHistopathology and pathogenesis of caerulein-, duct ligation-, and arginine-induced acute pancreatitis in Sprague-Dawley rats and C57BL6 Mice(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Zhang, Jun; Rouse, Rodney L.Three classical rodent models of acute pancreatitis were created in an effort to identify potential pre-clinical models of drug-induced pancreatitis (DIP) and candidate non-invasive biomarkers for improved detection of DIP. Study objectives included designing a lexicon to minimize bias by capturing normal variation and spontaneous and injury-induced changes while maintaining the ability to statistically differentiate degrees of change, defining morphologic anchors for novel pancreatic injury biomarkers, and improving understanding of mechanisms responsible for pancreatitis. Models were created in male SpragueDawley rats and C57BL6 mice through: 1) administration of the cholecystokinin analog, caerulein; 2) administration of arginine; 3) surgical ligation of the pancreatic duct. Nine morphologically detectable processes were used in the lexicon; acinar cell hypertrophy; acinar cell autophagy; acinar cell apoptosis; acinar cell necrosis; vascular injury; interstitial edema, inflammation and hemorrhage; fat necrosis; ductal changes; acinar cell atrophy. Criteria were defined for scoring levels (0= absent, 1= mild, 2= moderate, 3= severe) for each lexicon component. Consistent with previous studies, histopathology scores were significantly greater in rats compared to mice at baseline and after treatment. The histopathology scores in caerulein and ligation-treated rats and mice were significantly greater than those of arginine-treated rats and mice. The present study supports a multifaceted pathogenesis for acute pancreatitis in which intra-acinar trypsinogen activation, damage to acinar cells, fat cells, and vascular cells as well as activation/degranulation of mast cells and activated macrophages all contribute to the initiation and/or progression of acute inflammation of the exocrine pancreas.
- PublicationOpen AccessIncreased endometrial expression of CC-chemokine receptor-1 in women with adenomyosis(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Xu, Hong; Yang, Yanfeng; Zhou, Caiyun; Huang, Xiufeng; Lin, Jun; Zhang, XinmeiAbnormal endometrial expression of CCchemokine receptor-1 (CCR1) may play a role in the pathogenesis of endometriosis. Adenomyosis, also called endometriosis interna, occurs when the endometrium invades the myometrium. The objective of this study was to determine CCR1 expression in endometrium in women with adenomyosis as compared to women without adenomyosis. We evaluated endometrial mRNA and protein expression in women with and without adenomyosis using quantitative polymerase chain reaction (PCR), immunohistochemical staining and western blot analysis, respectively. We detected CCR1- immunoreactive expression in endometrium in all women with and without adenomyosis. CCR1- immunoreactive staining in endometrial cells was significantly higher in women with adenomyosis (4.89±1.06) compared to those without adenomyosis (2.21±1.16, P<0.001). Women with adenomyosis had higher levels of CCR1 mRNA in endometrium compared to women without adenomyosis (P<0.05). CCR1 protein levels in endometrium were significantly higher in women with adenomyosis (1.66±0.79) compared to women without adenomyosis (0.56±0.13, P<0.001), and positively correlated with the severity of dysmenorrhea (r=0.87, P<0.001). These results suggest that increased CC-chemokine receptor expression may play a role in the pathogenesis of adenomyosis.