Histology and histopathology Vol.24, nº1 (2009)
Permanent URI for this collection
Browse
Browsing Histology and histopathology Vol.24, nº1 (2009) by Issue Date
Now showing 1 - 13 of 13
Results Per Page
Sort Options
- PublicationOpen AccessBone marrow stromal cells for spinal cord repair, A challenge for contemporary neurobiology(Murcia : F. Hernández, 2009) Vaquero, J.; Zurita, M.In the last years, it has been reported that bone marrow stromal cells (BMSC) are able to differentiate towards a neuronal phenotype, in vitro as well as in vivo, and consequently, the possible use of these cells for the treatment of neurological diseases has acquired enormous importance. The objective of this review is to discuss the experimental findings that suggested the utility of BMSC for the treatment of paraplegia, and the possibilities of its clinical application in patients. For this reason, we revise our previous experimental findings about neuronal transdifferentiation of BMSC, and the utility of local BMSC transplantation in an experimental model of chronic paraplegia. Our current experience supports that a neural transdifferentiation of BMSC is possible after these mesenchymal stem cells are transplanted into injured spinal cord tissue. Furthermore, this cell therapy achieves a clear functional improvement of paraplegic animals, together with morphological evidence of spinal cord regeneration. Although at present our efforts should be guided to obtain a better knowledge of the mechanisms of nervous regeneration induced by bonemarrow derived stem cells, it is obvious that cell therapy for nervous system repair is beginning, and BMSC transplantation offers new hope for the treatment of traumatic paraplegia in humans.
- PublicationOpen AccessGenetic and molecular alterations in rhabdomyosarcoma: mRNA overexpression of MCL1 and MAP2K4 genes(Murcia : F. Hernández, 2009) Pazzaglia, Laura; Chiechi, Antonella; Conti, Amalia; Gamberi, Gabriella; Magagnoli, Giovanna; Novello, Chiara; Morandi, Luca; Picci, Piero; Mercuri, Mario; Benassi, M.S.Rhabdomyosarcoma, the most common soft tissue sarcoma in childhood, belongs to the small round cell tumor family and is classified according to its histopathological features as embryonal, alveolar and pleomorphic. In this study we propose to explore genetic alterations involved in rhabdomyosarcoma tumorigenesis and assess the level of mRNA gene expression of controlling survival signalling pathways. For genetic and molecular analysis, array-based comparative genomic hybridization, combined with Real Time PCR using the comparative method, was performed on 14 primary well-characterized human primary rhabdomyosarcomas. Multiple changes affecting chromosome arms were detected in all cases, including gain or loss of specific regions harbouring cancer progression-associated genes. Evaluation of mRNA levels showed in the majority of cases overexpression of MCL1 and MAP2K4 genes, both involved in cell viability regulation. Our findings on rhabdomyosarcoma samples showed multiple copy number alterations in chromosome regions implicated in malignancy progression and indicated a strong expression of MAP2K4 and MCL1 genes, both involved in different biological functions of complicated signalling pathways.
- PublicationOpen AccessBRCA1 expression and molecular alterations in familial breast cancer(Murcia : F. Hernández, 2009) Mangia, Anita; Chiriatti, Annalisa; Tommasi, Stefania; Menolascina, Filippo; Petroni, Stella; Zito, Francesco A.; Simone, Giovanni; Schittulli, Francesco; Paradiso, AngeloThe aim of the study was to evaluate the performance of immunohistochemical MS110 expression in a series of familial and sporadic breast cancer patients. An immunohistochemical study was performed on TMA samples from 93 sporadic and 94 familial breast cancer patients with (7/94) and without BRCA1 germline mutations. BRCA1 protein expression level was evaluated using the monoclonal MS110 antibody. Immunohistochemistry, performed on TMA samples, showed positive nuclear staining for BRCA1 in 34 sporadic and 37 familial breast tumours, respectively. All the tumours from patients carrying BRCA1 mutations showed complete loss of both BRCA1 and ERa expression, regardless of the type of mutation. The percentage of MS110 positive cases was significantly lower in mutated versus wild type BRCA1 familial cases (p=0.02) while the percentage of patients with higher ERa expression was significantly lower in BRCA1- mutated versus BRCA1-wild type familial patients (p=0.05). Interestingly, the presence of the E1038G polymorphism in BRCA1 exon 11 was significantly associated with protein expression (p=0.029). The frequency of MS110 negative cases also detected in BRCA1-wild type tumours, points to the inability of the BRCA1 IHC expression in discriminating between familial and sporadic breast cancer.
- PublicationOpen AccessMacrophage populations and expressions of regulatory proinflammatory factors in the rat meninx under lipopolysaccharide treatment in vivo and in vitro(Murcia : F. Hernández, 2009) Yamate, J.; Ishimine, S.; Izawa, T.; Kumagai, D.; Kuwamura, M.Macrophages play important roles in host defense mechanisms. In the brain, besides microglial cells, meningeal macrophages are present. However, the pathobiological characteristics of meningeal macrophages in rats remain to be investigated. In normal meninx, immunohistochemically, macrophages reacting to CD163 (macrophage scavenger receptor) and major histocompatibility complex (MHC) class II-expressing cells (involving activated macrophages or dendritic cells) were sporadically seen without age-dependent changes. Injection of lipoplysaccharide (LPS) (5 μg; Escherichia coli) into the cerebrum increased the number of anti-CD68-positive macrophages (with greater phagocytic activity) in the meninx, with a peak at 12 h during observation period until 48 h; MHC class IIexpressing cells showed a gradual increase in number from 3 h after injection; however, anti-CD163-positive macrophages did not show significant change. In in vitro studies, LPS (0, 0.02, 0.05, 0.5, 5, 50 and 100 μg/ml) was added to KMY-1 or KMY-2 cells, both of which had been established from a rat malignant meningioma. KMY-1 originally reacted to CD163, but LPS addition at 0.5 μg/ml and greater concentrations decreased the anti- CD163-positive cell number and instead increased the anti-CD68-positive cell number. LPS-treated KMY-2 increased the anti-CD163-positive cell number at 0.05 and 0.5 μg/ml. By RT-PCR methods, LPS (0, 0.5, 5, 50, and 100 μg/ml)-treated KMY-1 and KMY-2 showed an increase in mRNA of monocyte chemoattractant protein- 1 (MCP-1, a chemokine), and LPS-treated KMY-2 increased mRNA of nerve growth factor (NGF, an immunological effecter). Collectively, under LPS treatment, macrophages with heterogeneous functions appear in rat meninx; rat meninx-forming cells may be involved in pathogenesis of meningeal inflammation by expressing different immunophenotypes and by producing regulatory proinflammatory factors such as MCP-1 and NGF.
- PublicationOpen AccessAltered growth pattern, not altered growth per se, is the hallmark of early lesions preceding cancer development(Murcia : F. Hernández, 2009) Doratiotto, Silvia; Marongiu, Fabio; Faedda, Simona; Pani, Paolo; Laconi, EzioMany human solid cancers arise from focal proliferative lesions that long precede the overt clinical appearance of the disease. The available evidence supports the notion that cancer precursor lesions are clonal in origin, and this notion forms the basis for most of the current theories on the pathogenesis of neoplastic disease. In contrast, far less attention has been devoted to the analysis of the phenotypic property that serves to define these focal lesions, i.e. their altered growth pattern. In fact, the latter is often considered a mere morphological by-product of clonal growth, with no specific relevance in the process. In the following study, evidence will be presented to support the concept that focal growth pattern is an inherent property of altered cells, independent of clonal growth; furthermore, it will be discussed how such a property, far from being merely descriptive, might indeed play a fundamental role in the sequence of events leading to the development of cancer. Within this paradigm, the earliest steps of neoplasia should be considered and analysed as defects in the mechanisms of tissue pattern formation.
- PublicationOpen AccessImmunohistochemical and lectin histochemical analysis of the alpaca efferent ducts(Murcia : F. Hernández, 2009) Parillo, F.; Magi, G.E.; Diverio, S.; Catone, G.An immunohistochemical and lectin histochemical study of the efferent ducts was performed in the alpaca. Two types of epithelium, consisting of principal and ciliated cells, were detected on the basis of the different cytokeratins expression and lectin binding pattern. AE1/AE3 and 13 cytokeratin antibodies intensely immunostained the entire cytoplasm of type I PCs, whereas AE1/AE3, but not anti cytokeratin 13, immunoreacted in type II principal cells along the apical, lateral and basal plasma-membrane. The histochemical characterization of the epithelial cells was carried out using a battery of different lectins: Con-A, UEA-I, LTA, WGA, GSA-II, GSA-IB4, SBA, PNA, ECA, DBA, MAL-II and SNA. Sialidase digestion and deglycosilation pre-treatments were also employed. In type I principal cells, the staining of the Golgi zone was interpreted giving evidence for the synthesis and secretion of O- and N-linked oligosaccharides. In particular, a-Man/a-Glc, GlcNAc, ß-Gal-(1-4)-GlcNAc, Neu5Aca2,3Gal and Neu5Aca2,6Gal/GalNAc residues were included in both O- and N-linked glycans, whereas a-Fuc, ß-GalNAc and a-Gal were only found in Olinked oligosaccharides; a-GalNac and ß-Gal-(1-3)-DGalNAc were found subterminal to sialic acid moieties and they were included in O- and N-glycans. In type II principal cells, the lectin staining was observed in the apical cytoplasmic granules and in vacuoles that were interpreted as components of an elaborate endocytotic apparatus specialized for the uptake of particulate material and fluid from the lumen. These results suggest the existence of two structurally different epithelial segments along the ductuli efferentes of the alpaca, with a high degree of compartmentalization of the secretory and absorptive activities.
- PublicationOpen AccessZNT7 and Zn2+ are present in different cell populations in the mouse testis(Murcia : F. Hernández, 2009) Chi, Zhi-Hong; Feng, Wan-Yu; Gao, Hui-Ling; Zheng, Wei; Huang, Liping; Wang, Zhan-YouThe aim of the present study was to investigate the relation of the spatial distribution between ZNT7 and chelatable zinc ions in the mouse testis. Immunohistochemical results demonstrated a wide distribution of ZNT7 in both seminiferous tubules and interstitial tissues of the testis. The spermatocytes and spermatids in the seminiferous tubules showed strong ZNT7 immunoreactivity whereas zinc autometallographic (AMG) staining was absent. Spermatozoa showed a high level of free zinc, but were void of ZNT7 immunoreactivity. No ZNT7 immunoreactivity and AMG grains were found in spermatogonia. Both ZNT7 and chelatable zinc were detected in Sertoli and Leydig cells. Furthermore, double immunofluorescence study demonstrated that the ZNT7 staining overlapped with that of TGN38 (a trans-Golgi marker), suggesting that ZNT7 was localized in the Golgi apparatus in the ZNT7- positive cells. In conclusion, ZNT7 and chelatable zinc were distributed in different cell populations except for Sertoli and Leydig cells in the mouse testis. ZNT7 may be involved in zinc transportation into the Golgi apparatus for protein packaging in the mouse testis
- PublicationOpen AccessDistinctive immunohistochemical profile of mucinous cystic neoplasms of pancreas, ovary and lung(Murcia : F. Hernández, 2009) Silverman, Jan F.; Zhu, Bing; Liu, Yulin; Lin, XiaoqiMucinous cystic neoplasms (MCNs) of the pancreas, ovary and lung have a similar histologic appearance. We investigated if immunohistochemical (IHC) studies could help in separating these neoplasms. Twenty-six ovarian MCNs (invasive carcinoma and borderline tumor), 12 pancreatic MCNs (invasive carcinoma, and with moderate or high-grade dysplasia), and 3 pulmonary MCNs (only invasive carcinoma) were retrieved. Our study demonstrated that pancreatic MCNs are positive for CDX-2 (67%), PDX-1 (100%), CK7 (83%) and CK20 (100%), while are negative for CA- 125. The IHC profile of ovarian intestinal type MCN is similar to that of pancreatic MCNs, except for lower frequency of CDX-2 expression (29% vs. 67%). Ovarian endocervical like MCNs are positive for CA-125 (100%) and CK7 (100%), while are negative for CDX-2, PDX-1 and CK20. Pulmonary MCNs are positive for CDX-2 (100%), CK7 (100%) and CK20 (100%), while are negative for PDX-1 and CA-125. All tumors are negative for TTF-1, D2-40 and WT-1. We concluded that an IHC panel of CDX-2, PDX-1, CA-125, and CK20 is useful in separating MCNs of the pancreas, ovary and lung.
- PublicationOpen AccessMitochondrial cholesterol in health and disease(Murcia : F. Hernández, 2009) Garcia-Ruiz, Carmen; Mari, Monserrat; Colell, Ana; Morales, Albert; Caballero, Francisco; Montero, Joan; Terrones, Ohiana; Basañez, Gorka; Fernández-Checa, José C.Cholesterol is a critical component of biological membranes, which not only plays an essential role in determining membrane physical properties, but also in the regulation of multiple signaling pathways. Cells satisfy their need for cholesterol either by uptake from nutrients and lipoproteins or de novo synthesis from acetyl-CoA. The latter process occurs in the endoplasmic reticulum, where transcription factors that regulate the expression of enzymes involved in the de novo cholesterol synthesis reside. Cholesterol is distributed to different membranes most prominently to plasma membrane, where it participates in the physical organization of specific membrane domains. Mitochondria, however, are considered cholesterol-poor organelles, and obtain their cholesterol load by the action of specialized proteins involved in its delivery from extramitochondrial sources and trafficking within mitochondrial membranes. Although mitochondrial cholesterol fulfills vital physiological functions, such as the synthesis of bile acids in the liver or the formation of steroid hormones in specialized tissues, recent evidence indicates that the accumulation of cholesterol in mitochondria may be a key step in disease progression, including steatohepatitis, carcinogenesis or Alzheimer disease.
- PublicationOpen AccessGalectin-7, will the lectinrsquos activity establish clinical correlations in head and neck squamous cell and basal cell carcinomas?(Murcia : F. Hernández, 2009) Câda, Z.; Chovanec, M.; Smetana, K. Jr.; Betka, J.; Lacina, L.; Plzák, J.; Kodet, R.; Stork, J.; Lensch, M.; Kaltner, H.; André, S.; Gabius, H.J.The human lectin galectin-7 (Gal-7; p53- induced gene-1) has anti- and pro-malignant features in different in vitro models. We tried to clarify relation of its expression to cellular and clinical parameters in head and neck squamous and basal cell carcinomas. Using a non-cross-reactive antibody, immunohistochemical staining in squamous cell epithelia (epidermis, epithelium of oropharynx and larynx) (n = 57), squamous cell carcinomas (n = 47) and lymph node metastases (n = 25), as well as basal cell carcinomas (n = 10) were studied. This monitoring was flanked by processing to assess the level of differentiation (cytokeratins 10 and 14), proliferation (Ki67) and basal lamina formation (collagen IV). The results were correlated with clinical and pathological findings (grading, TNM-staging, extracapsular spread, angio- and lymphangioinvasion, perineural invasion, recurrence and survival). Gal-7 resides in all layers of epithelia with cytoplasmic and nuclear localization in normal specimens. Basal cell carcinomas were devoid of the Gal-7 respective signal. Squamous cell carcinomas were positive, presenting different staining profiles. Intense staining was predominantly found in squamous cell cancers with high degrees of differentiation and keratinization. Fittingly, poor level of differentiation (P = 0.0009), absence of keratinization (P = 0.0105) and significant discontinuity or absence of collagen IV expression in the peritumoral basal lamina (P = 0.0024). was found in Gal-7-negative tumors. Gal-7 presence was not related to gender, primary tumor site, T-stage, Nstage, clinical stage, extracapsular spread, angio- and lymphangioinvasion, perineural spread or treatment outcome at a statistically significant level. Immunohistochemical analysis revealed a positive correlation for differentiation and keratinization to Gal-7 presence in squamous cell carcinomas. Absence of Gal-7 expression was detected in basal cell carcinomas. These clinical data delineate Gal-7 influence on differentiation in vivo, without evidence for a role in dissemination reported for lymphoma.
- PublicationOpen AccessAn innovative methodology for the automated morphometric and quantitative estimation of liver steatosis(Murcia : F. Hernández, 2009) Liquori, Giuseppa Esterina; Calamita, Giuseppe; Cascella, Davide; Mastrodonato, Maria; Portincasa, Piero; Ferri, DomenicoThe management of liver steatosis, due to its potential evolution towards severe diseases, requires accurate diagnosis. Fatty infiltration in liver diseases is commonly assessed histologically by semi-quantitative methods, which can be subjective. Automated computerized procedures using commercial software for image analysis have also been recently employed. The aim of the study was to develop an innovative automated computerized procedure to accurately evaluate both the morphometry and degree of lipid accumulation in liver. Fatty infiltration was assessed in paraffin- and resinembedded samples of steatotic livers from rats undergoing 0, 3, 7, 14, and 30-day choline-deficient diet, and from liver biopsy of a morbidly obese patient undergoing bariatric surgery. Specific software was developed, which works with a morphological operator, in addition to a chromatic one to select lipid droplets. The choline-deficient diet induced steatosis with a gradual shift from micro- to macro-vesicular. In paraffin sections, the macrovesicles-to-microvesicles ratio and the degree of steatosis, when using only the chromatic operator, produced overestimates. Results were consistent in both rat and human samples. An improvement of topographic, morphometric and quantitative estimation of fatty liver infiltration is obtained with our software, working with a morphological operator and using semi-thin sections from resin-embedded samples. This innovative procedure may be applied to human liver samples, offering promising diagnostic and prognostic perspectives.
- PublicationOpen AccessThe pathology of APP transgenic mice, a model of Alzheimer’s disease or simply overexpression of APP?(Murcia : F. Hernández, 2009) Howlett, D.R.; Richardson, J.C.Alzheimer’s disease (AD) is characterized by a number of pathological features, notably extracellular senile plaques composed of the beta-amyloid protein (Aß) and neurofibrillary tangles (NFT’s), which are intracellular inclusions of hyperphosphorylated tau protein. In their attempts to generate a model of AD, many laboratories have produced transgenic mice that overexpress the amyloid precursor protein (APP), in particular, mutant APP which is associated with familial forms of AD in man. Histopathological assessment shows that APP transgenic mice demonstrate an accumulation of Aß in plaques from an early age; these plaques are invariably surrounded by activated inflammatory cells such as astrocytes and microglia, as is common in AD brain. Also, commonly associated with the plaques is hyperphosphorylated tau, although this does not take on the NFT phenotype observed in AD. Atrophy and neurodegenerative pathology are other common features of AD; some neuronal loss is evident in close proximity to plaques in APP transgenic mice although this is not extensive. Consequently, it is evident that APP transgenic mice exhibit, to some degree, many of the pathological features of AD.
- PublicationOpen AccessRUNX3 expression correlates with chief cell differentiation in human gastric cancers(Murcia : F. Hernández, 2009) Naotaka Ogasawara; Tetsuya Tsukamoto; Tsutomu Mizoshita; Ken-ichi Inada; Hisayo Ban; Shinya Kondo; Shinji Takasu; Toshikazu Ushijima; Kosei Ito; Yoshiaki Ito; Masao Ichinose; Takafumi Ogawa; Takashi Joh; Masae TatematsuRUNX3 is a novel tumor suppressor in gastric carcinogenesis and an important factor for differentiation of chief cells in the normal gastric fundic mucosa. In this study, we confirmed RUNX3 immunolocalization in the fundic gland (bottom part) but minimum in surface mucous cell epithelium (top part) in the isolated gland from fundic mucosa. We also analyzed RUNX3 expression by immunohistochemistry in 102 gastric cancers and made a histological assessment of the expression of differentiation markers to evaluate interrelations. Among them, 45 and 57 cases were judged to be RUNX3 positive and negative, respectively, and 33 and 69 cases were pepsinogen I positive and negative, with no link to histological types. RUNX3 expression was significantly associated with that of pepsinogen I (P<0.001), but not mucins, including MUC5AC and MUC6, or the parietal or intestinal phenotypes. In conclusion, the present study showed, for the first time to our knowledge, a relation between RUNX3 and pepsinogen I expression in human gastric cancers. RUNX3 is strongly associated with chief cell phenotypic expression in human gastric cancers, as well as in normal gastric mucosa, and could be considered to play an important role in maintaining the chief cell phenotype.