Histology and histopathology Vol.32, nº4 (2017)
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- PublicationOpen AccessLisinopril has a cardio-protective effect on experimental acute autoimmune myocarditis in rats(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Atteya, Muhammad; Mohamed, Raeesa A.; Ahmed, Aly M.; Abdel Baky, Nayira A.; Alfayez, Musaad A.; Almalke, Hatim D.; El Fouhil, Ahmed F.The present study investigated the effect of lisinopril on experimental autoimmune myocarditis (EAM) in rats, a histologically similar model to human acute myocarditis. Animals and methods. Twenty four, six week-old male Wistar rats were randomly allocated into 4 groups of 6 rats each. Group I received no treatment. Group II received lisinopril at a dose of 15 mg/kg/day suspended in 1 ml of 2% gum acacia daily, from day 1 to day 21. To induce myocarditis, animals of groups III and IV were injected by 1 mg of porcine cardiac myosin on days 1 and 8. In addition, animals of group IV received lisinopril in gum acacia daily, from day 1 to day 21. All rats were sacrificed on day 21. Serum levels of creatine phosphokinase, troponin-T, tumor necrosis factor-α and interleukin-6 were estimated. Hearts were processed for histopathological, as well as immunohistochemical study for thioredoxin (TRX) immunoreactivity. Results. The wall of hearts from rats of myocarditislisinopril group showed mild focal myocarditis and a significant decrease of the mean percentage of pyknotic nuclei in cardiomyocytes, coincident with a significant decrease in serum biomarkers levels and TRX immunoreactivity, compared to myocarditis group. Conclusion. The present study suggested a cardioprotective effect of lisinopril on acute EAM in rats, probably through a mechanism related to its suppressive effect on angiotensin II formation.
- PublicationOpen AccessThe proliferation mechanism of normal and pathological human placentas(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Unek, Gozde; Ozmen, Asli; Sitki Isenlik, Bekir; Turkay Korgun, EminThe placenta, which is a regulator organ for many metabolic activities between mother and fetus, is critical in influencing the outcome of pregnancy. Therefore, fetal growth is directly related to the placental development. Placental development depends on the coordinated action of trophoblast proliferation, differentiation and invasion. Studies on cell cycle related proteins that control these events are limited. Abnormal placental development is linked to various pregnancy pathologies such as preeclampsia, intrauterine growth restriction, diabetes mellitus and gestational trophoblastic diseases. The cell cycle mechanism of human placenta should be well understood for a healthy pregnancy outcome. Moreover, how cell cycle related proteins that control placental development are affected in pregnancy pathologies is not fully understood yet. Therefore, the aim of this review is to address the currently available knowledge on cell cycle regulatory proteins involved in human placental development and on the expression differences of these proteins in pathological placentas.
- PublicationOpen AccessHistopathological and clinical expression of periodontal disease related to the systemic inflammatory response(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Ionel, Anca; Lucaciu, Ondine; Tăbăran, Flaviu; Berce, Cristian; Toader, Septimiu; Hurubeanu, Lucia; Bondor, Cosmina; Câmpian, Radu S.Periodontal disease with its systemic implications is highly prevalent among the population, and this correlation could have an impact on the quality lives of many humans. The purpose of this study was to assess the clinical and histopathological changes of the periodontium correlated with the systemic inflammatory response in periodontal disease. An experimental study was performed on male Wistar rats which were subjected to a procedure of periodontitis induction through placing silk thread ligatures around the lower incisors, under general anesthesia. Clinically, the changes of the periodontal tissue induced by the periodontitis progression were daily assessed. Two blood samples were obtained from each animal, at baseline and on completion of the experiment. The plasma level of the cytokine IL-6 and haematological parameters such as leukocytes, neutrophils, lymphocytes, monocytes, and platelets were determined. After seven days the animals were sacrificed, and samples were prepared for histological evaluation. Clinical manifestations such as changes in the color, contour and consistency of the gingival tissue and the bleeding on probing were registered. Histopathological analysis showed an intense inflammatory cell infiltration, the presence of osteoclasts and an obvious bone resorption activity. A significant increase in IL-6 values during the progression of periodontitis in rats (p<0.001) was also observed. The results of this research demonstrated that the clinical and histological changes in the rat’s periodontium are correlated with a notable systemic inflammatory response. Therefore, periodontitis control can be inserted as part of the programs of systemic disorders prevention, in clinical practice.
- PublicationOpen AccessImaging the lung: the old ways and the new(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Poobalasingam, Thanushiyan; Salman, David; Li, Henry; Alçada, Joana; Dean, Charlotte H.Our understanding of lung biology can be greatly enhanced by studying embryonic and postnatal lung development, and the perturbations which occur during disease. Imaging techniques provide a unique insight into these processes. A wide variety of imaging techniques have been used to study the lungs at various stages of development and disease, ranging from histological stains to more novel techniques such as single plane illumination microscopy (SPIM), intravital microscopy (IVM), and micro-computed tomography (micro-CT). Each of these tools can be used to elicit different information about the lungs and each has its own unique advantages and disadvantages for pulmonary research. In this review we assess some of the most commonly-used and novel imaging techniques available for lung research today.
- PublicationOpen AccessExpression of p53 and isoforms in beningn and malignant lesions of the head and neck(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Trovato, M.C.; Ruggeri, R.M.; Guzzo, E.; Certo, R.; Alibrandi, A.; Scifo, S.; Scardigno, M.; Vitarelli, E.; Arena, G.; Gambadoro, O.; Catalano, N.; Bourdon, J.C.; Galletti, B.; Galletti, F.; Cavallari, V.Background. P53, a crucial suppressor of tumor formation, generates multiple isoforms, whose role in disease is still being defined. Methods. By immunohistochemistry, we studied the expression of P53 protein and relative isoforms in benign papillomas (PA, n=9), inverted papilloma (IPA, n=10) and squamous cell carcinomas (SCC, n=21). Results. In all lesions, P53 isoforms were significantly more expressed than P53. Immunoexpression of P53 matched with P53 isoforms in IPA as well as in SCC. Simultaneous immunoexpression of P53 and related isoforms was double in SCC compared to IPA (10% vs 24%), while expression of P53 isoforms was strongly reduced (70% vs 43%). IPA showed the highest percentage of both reactive cases and immunostained cells expressing P53 isoforms. Conclusions. We found the higher expression of P53 isoforms in IPA and SCC compared to PA, suggesting their role in local aggressiveness and malignant proliferation in head-neck lesions.
- PublicationOpen AccessMixed epithelial and stromal tumor of kidney with renal vein extension: an unusual case report and review of literature(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Xie, Wen Lin; Lian, Jia Yan; Li, Bin; Tian, Xiao Ying; Li, ZhiMixed epithelial and stromal tumor of kidney (MESTK) is a rare but distinct renal complex neoplasm composed of a mixture of mesenchymal and epithelial elements with characteristic ovarian-type stroma. Due to its relative rarity, little is known about the histogenesis and prognostic factors of this tumor. Although most reported cases display bland histological features and benign clinical course, a few cases of malignant MESTK have been described. We report an unusual case of MESTK in a 50-year-old female patient with renal venous involvement. Macroscopically, the tumor was solid and unencapsulated in the central region of left kidney. There was a polypoid mass with slender pedicle found to extend into the renal vein forming an intravenous tumor thrombus. Histologically, both renal and intravenous mass were composed of bland spindleshaped cells and round dilated tubules lined by epithelium without any cytological atypia. The spindle cells were diffusely positive for smooth muscle actin and desmin, while tubules were positive for pan-cytokeratin (AE1/AE3). A diagnosis of MESTK with renal vein extension was made. The patient received no adjuvant treatment after radical nephrectomy. There was no sign of recurrence or metastasis of tumor found in a period of 16-month regular follow-up. To our knowledge, this is the first case of MESTK with renal vein extension, but lacking malignant histological appearance. Additional studies of MESTK with vein involvement will be needed to determine whether this imparts any adverse behavior, similar to other benign renal tumors with vascular involvement.
- PublicationOpen AccessImmunohistochemical assessment of cell populations in leprosy-spectrum lesions and reactional forms(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Fachin, Luciana Raquel Vincenzi; Soares, Cleverson Teixeira; Belone, Andrea de Faria Fernandes; Trombone, Ana Paula Favaro; Rosa, Patrícia Sammarco; Guidella, Cássio Cesar; Franco, Marcello FabianoIn situ immunophenotyping of leprosy lesions can improve our understanding of the biology of inflammatory cells during the immune response to Mycobacterium leprae antigens. In the present study, biopsies from 10 healthy controls and 70 leprosy patients were selected, 10 for each of the following conditions: clinical tuberculoid (TT), borderline tuberculoid (BT), borderline borderline (BB), borderline lepromatous (BL), lepromatous (LL), reversal reaction (R1), and erythema nodosum leprosum (R2). Qualitative and quantitative immunohistochemical analyses were performed to detect CD3, CD4, CD8, FoxP3, CD20, CD138, CD1a, CD57, CD15, CD117, CD68, and CD163. In addition, histochemistry was employed to identify eosinophils. The amount of CD3+ and CD4+ T cells was higher in TT than in LL patients. CD8+ T cells were predominant in T lymphocyte infiltrations in the basal layer of the epidermis. The number of FoxP3+ cells was similar among different forms of the disease, but was higher in BL and LL than in R2 individuals. CD20+ lymphocytes were most abundant in TT samples, while CD138+ plasma cells displayed no detectable differences. Epithelioid macrophages from the center of TT and R1 granulomas exhibited the M1 phenotype (CD68+CD163- ), whereas those in LL granulomas showed the M2 phenotype (CD68+CD163+). There was a gradual decrease in the amount of CD1a+ cells from the TT towards the LL form of the disease. A significant increase in the number of neutrophils was observed only in R2 samples. All the cells investigated, except eosinophils, participated in the immunopathogenesis of leprosy.
- PublicationOpen AccessExpression of Ccdc85C, a causative protein for murine hydrocephalus, in the mammary gland tumors of dogs(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Tanaka, Natsuki; Izawa, Takeshi; Takenaka, Shigeo; Akiyoshi, Hideo; Yamate, Jyoji; Kuwamura, MitsuruCoiled-coil domain containing 85c (Ccdc85c) is a causative gene for hemorrhagic hydrocephalus mouse which shows hydrocephalus with frequent brain hemorrhage and formation of subcortical band heterotopia. A previous study revealed that Ccdc85C protein is expressed in the systemic simple epithelial cells with proliferative activity in rats and suggested that Ccdc85C expression may be related to the cell proliferation of simple epithelial cells. To reveal the roles of Ccdc85C in the proliferative lesion, we examined the expression patterns of Ccdc85C in the mammary gland tumor of dogs, a common representative tumor derived from simple epithelial cells. In canine mammary gland tumors, Ccdc85C was expressed at the apical junctions of the luminal epithelial cells. Ccdc85C was also distributed throughout the entire cytoplasm of the myoepithelial cells. Ccdc85C expression was observed at the epithelial cells with luminal structures, but was not observed at the epithelial cells forming sheet growth pattern without luminal structure. In carcinomas, Ccdc85C expression in mammary tumor tissue tended to be weaker than that in surrounding normal mammary gland tissue. Ccdc85C is known to cause neurological diseases such as hydrocephalus, and subcortical heterotopia, and the present study is the first to demonstrate Ccdc85C expression in canine mammary tumors and a relationship between Ccdc85C expression and tumor malignancy
- PublicationOpen AccessNotch1 in oral squamous cell carcinoma(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Yoshida, Ryoji; Ito, Takaaki; Abdo Hassan, Wael; Nakayama, HidekiNotch signaling has been reported to be involved in several types of malignant tumors. However, the role and activation mechanisms of Notch signaling in oral squamous cell carcinoma (OSCC) remain poorly characterized. The present review focuses on the dual role of Notch signaling in OSCC. A number of expression and functional analyses demonstrated that Notch1 plays a crucial role in development and progression of OSCC. On the other hand, a tumor suppressive role of Notch1 was also suggested from studies, based on deep sequencing of cancer genomes. Interestingly, although some Notch1 mutations overlap in tumors from Caucasian and Asian patients, the overall spectrum of such mutations is vastly different between these cohorts. Accumulating evidence suggests that variation of Notch1 mutation signature may determine the role of Notch signaling in OSCC. As Notch is thought to act as an oncogene in a subset of OSCC, but also has a tumor suppression role, the role of Notch in OSCC seems to be highly context dependent.
- PublicationOpen AccessHexokinase 2 in colorectal cancer: a potent prognostic factor associated with glycolysis, proliferation and migration(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Katagiri, Munetoshi; Karasawa, Hideaki; Takagi, Kiyoshi; Nakayama, Shun; Yabuuchi, Shinichi; Fujishima, Fumiyoshi; Naitoh, Takeshi; Watanabe, Mika; Suzuki, Takashi; Unno, Michiaki; Sasano, HironobuBackground. It is well known that proliferating carcinoma cells preferentially use aerobic glycolysis rather than oxidative phosphorylation for energy production. Hexokinase 2 (HK2) plays a pivotal role in the glycolytic pathway. Previous studies have demonstrated that HK2 activity is markedly increased in various malignant neoplasms, but the clinical and biological significance of HK2 remain largely unclear in the colorectal carcinoma. Patients and methods. We performed immunohistochemistry for HK2 in 195 colorectal carcinoma tissues. We also used HCT8 and HT29 colon carcinoma cells in in vitro studies. Results. HK2 immunoreactivity was detected in 100 out of 195 (51%) colorectal carcinoma tissues, and the immunohistochemical HK2 status was significantly associated with tumor size, depth of invasion, liver metastasis and TNM stage in these cases. Moreover, the HK2 status was significantly associated with increased incidence of recurrence and overall mortality of the patients, and multivariate analyses demonstrated that HK2 status was an independent prognostic factor for both disease-free and overall survival. Subsequent in vitro experiments revealed that both HCT8 and HT29 colon carcinoma cells transfected with specific siRNA for HK2 significantly decreased the lactate production, proliferation activity and migration property. Conclusion. These results suggest that HK2 plays important roles in the glycolytic, proliferation and migration properties of colorectal carcinoma and, therefore, HK2 status is a potent worse prognostic factor in colorectal cancer patients