Histology and histopathology Vol.27, nº11 (2012)
Permanent URI for this collection
Browse
Browsing Histology and histopathology Vol.27, nº11 (2012) by Issue Date
Now showing 1 - 12 of 12
Results Per Page
Sort Options
- PublicationOpen AccessExperimental diabetes modulates collagen remodelling of joints in rats(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Atayde, Sandra A.; Yoshinari, Natalino H.; Nascimento, Dafne P.; Catanozi, Sérgio; Andrade, Priscila C.; Velosa, Ana Paula P.; R. Parra, Edwin; Passarelli, Marisa; Nakandakare, Edna R.; Capelozzi, Vera L.; Teodoro, Walcy R.The aim of this study was to evaluate extracellular matrix components in articular cartilage, ligaments and synovia in an experimental model of diabetes. Young Wistar rats were divided into a streptozotocin-induced (STZ; 35 mg/kg) diabetic group (DG; n=15) and a control group (CG; n=15). Weight, blood glucose and plasma anti-carboxymethyllysine were measured 70 days after STZ infusions. Knee joints, patellar ligaments, and lateral and medial collateral ligaments were isolated and stained with hematoxylin-eosin and Picrosirius. The total collagen content was determined by morphometry. Immunofluorescence was employed to evaluate types I, III, and V collagen in ligaments and synovial tissues and types II and XI collagen in cartilage. Results: Higher blood glucose levels and plasma anti-carboxymethyllysine were observed in DG rats when compared to those in CG rats. The final weight was significantly lower in the DG rats than in the CG rats. Histomorphometric evaluation depicted a small quantity of collagen fibers in ligaments and articular cartilage in DG rats, as well as increased collagen in synovial tissue. There was a decrease in cartilage proteoglycans in DG rats when compared with CG rats. Immunofluorescence staining revealed an increase of collagen III and V in ligaments, collagen XI in cartilage, and collagen I in synovial tissue of DG rats compared with CG rats. Conclusion: The ligaments, cartilage and synovia are highly affected following STZ-induced diabetes in rats, due the remodeling of collagen types in these tissues. This process may promote the degradation of the extracellular matrix, thus compromising joint function. Our data may help to better understand the pathogenesis of joint involvement related to diabetes.
- PublicationOpen AccessGenes promoting and disturbing testis development(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Barrionuevo, Francisco J.; Burgos, Miguel; Scherer, Gerd; Jiménez, RafaelMammals have an XX/XY sex chromosomal sex determination system in which males represent the heterogametic sex. The Y-linked gene, SRY, determines sex by inducing the undifferentiated, bipotential gonads to differentiate as testes, which produce androgens and promote in this way the development of a male phenotype. Thus, in mammals, sex determination can be equated to testis determination, which involves several important cell processes, including Sertoli cell differentiation, mesonephric cell migration, testis cord formation, testis-specific vascularization, and myoid and Leydig cell differentiation. Many genes are currently known to be involved in testis development. Some of them, including SF1, WT1, GATA4 and FOG2, are necessary for the formation of the bipotential, undifferentiated gonad but also have important roles in testis differentiation. Others can be considered testis-promoting, differentaition and/or maintenance genes: these include SRY, SOX9, FGF9, PTGDS, SOX8, SOX3, NR0B1, PDGFR α , DMRT1, AMH, NGF, NTF3 and NGFR as the most important examples. Finally, there is a smaller group of genes which are involved in ovarian development and which can cause aberrant testis development if mutated, including RSPO1, WNT4, CTNNB1, FST, BMP2 and FOXL2. In this paper, we review our current knowledge on the function, spatio-temporal expression pattern and mutant sexual phenotypes associated with these genes, and discuss the various roles they play in gonad development.
- PublicationOpen AccessReview of renal oncocytosis (multiple oncocytic lesions) with focus on clinical and pathobiological aspects(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Kuroda, Naoto; Azusa, Tanaka; Ohe, Chisato; Mikami, Shuji; Nagashima, Yoji; Sasaki, Toyokazu; Inoue, Keiji; Hes, Ondrej; Michal, Michal; Brunelli, Matteo; Martignoni, GuidoRenal oncocytosis is a recently established disease entity characterized by numerous oncocytic tumors and diffuse involvement of oncocytic changes in renal parenchymal epithelia. In this article, we review this disease with a focus on its clinical and pathobiological aspects. Clinically, renal oncocytosis may occur in a sporadic form without any underlying disease or may be associated with chronic renal failure/long-term hemodialysis. However, Birt-Hogg- Dubé syndrome, characterized by skin tumors such as fibrofolliculoma or trichodiscoma, pulmonary lesions including bullae and spontaneous pneumothorax, and renal tumors should be evaluated in the differential diagnosis. The disease can develop either unilaterally or bilaterally. The involved renal parenchyma contains several to multiple brownish-colored nodules of varying size and is entirely replaced by lesions at the overt stage. Histologically, oncocytic tumors in both the dominant mass and smaller lesions encompass so-called hybrid tumor, chromophobe renal cell carcinoma (RCC), and renal oncocytoma (RO). Regarding renal parenchymal abnormalities, infiltrative growth of oncocytic cells, cortical cysts with oncocytic features, or extensive oncocytic change in non-neoplastic tubules can also be observed. Histochemical, immunohistochemical, and molecular genetic features of chromophobe RCC and RO arising in the setting of renal oncocytosis are generally identical to those in the sporadic type. However, hybrid tumors seem to be histologically distinct from chromophobe RCC and RO. In FISH analyses of some hybrid tumors, a gain of chromosomes 1, 2, 6, 10, and 17 was identified. In one tumor, no germ line mutation of folliculin gene was identified. Published data show that tumors follow a benign course. Further studies will be necesary to clarify the pathogenesis of renal oncocytosis.
- PublicationOpen AccessRegulation of neuronal and endothelial nitric oxide synthase by anabolic-androgenic steroid in skeletal muscles(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Fontana, Karina; Rocha, Thalita; da Cruz-Höfling, Maria AliceAnabolic-androgenic steroids (AAS) and exercise share comparable effects on myogenic differentiation, force development, fiber growth and skeletal muscle plasticity. The participation of nitric oxide synthase (NOS) on these effects was only demonstrated in response to exercise. Using immunohistochemistry and western blotting we examined the effect of AAS on the expression of NOS I and III isoforms in three muscles, distinct metabolically and physiologically: soleus (SOL), tibialis anterioris (TA) and gastrocnemius (GAS). Mice with a lipid profile akin to humans were used. Sedentary mice (Sed-C) or exercised, submitted to six-weeks of aerobic treadmill running (one hour/day, 5 days/week) were administered mesterolone (Sed-M and Ex-M, respectively) or gum arabic (vehicle, Ex-C) during the last three weeks, three alternate days per week. Consistently, The TA showed the strongest labeling and the SOL the weakest with NOS III predominating over NOS I. Mesterolone administered to sedentary mice (Sed-C x Sed-M) significantly upregulated NOS I in TA and SOL and NOS III in all three muscles. Mesterolone administered to exercised mice (Ex-C x Ex-M) upregulated NOS I in all three muscles and NOS III in TA and SOL. The exercise to mesterolone-treated mice (Sed-M x Ex-M) produced a strong increase in NOS I expression in GAS; in contrast it antagonized the mesterolone-induced upregulation of NOS I in TA muscle and NOS III in SOL and GAS. The data show nitric oxide (NO) as a potential signaling mediator of AAS effects in skeletal muscle and that NOS I and NOS III upregulations were muscle phenotype-specific. These may be regarded as an indication of the complex NOS/NO signaling mechanism related with AAS effects vs. metabolic/physiological muscle characteristics.
- PublicationOpen AccessRho GTPases and Nox dependent ROS production in skin. Is there a connection?(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Stanley, Alanna; Hynes, Ailish; Brakebusch, Cord; Quondamatteo, FabioRho GTPases are a family of small GTP binding proteins most commonly known for the regulation of many cellular processes, including actin cytoskeleton re-organisation, cell proliferation, signal transduction and regulation of apoptosis. Additionally, a link between Rho GTPases and reactive oxygen species (ROS) has been shown. In line with the growing interest in the role of ROS in cell biology, the relevance of this connection is becoming increasingly clearer. ROS production is classically associated with oxidative metabolic pathways (e.g. respiratory chain, arachidonic acid). During these metabolic pathways, ROS are produced as by-products and these can be potentially toxic. However, numerous cell types contain dedicated enzymatic complexes, i.e., NADPH oxidase (Nox) complexes, for regulated production of ROS. This regulated production of ROS seems to be important for a number of fundamental cell biological processes, including cell growth, differentiation, migration, angiogenesis, aimed at maintaining tissue homeostasis. Data suggests that skin cells are capable of a regulated ROS production via Nox complexes. Members of the Rho GTPase family have been found to play a central regulatory role in Nox activity. In the present review we will focus on the involvement of Rho GTPases in regulated production of ROS with special emphasis on the skin. We will also discuss the possibility that some in vivo effects of the deletion of members of the Rho GTPase family in skin cells could potentially be linked to a reduced ability of regulated ROS production.
- PublicationOpen AccessAngiotensinergic innervation of the kidney: Localization and relationship with catecholaminergic postganglionic and sensory nerve fibers(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Bohlender, Jürgen; Pfarrer, Beat; Patil, Jaspal; Nussberger, Jürg; Thalmann, Georg N. Thalmann; Imboden, HansWe describe an angiotensin (Ang) II-containing innervation of the kidney. Cryosections of rat, pig and human kidneys were investigated for the presence of Ang II-containing nerve fibers using a mouse monoclonal antibody against Ang II (4B3). Co-staining was performed with antibodies against synaptophysin, tyrosine 3-hydroxylase, and dopamine beta-hydroxylase to detect catecholaminergic efferent fibers and against calcitonin gene-related peptide to detect sensory fibers. Tagged secondary antibodies and confocal light or laser scanning microscopy were used for immunofluorescence detection. Ang II-containing nerve fibers were densely present in the renal pelvis, the subepithelial layer of the urothelium, the arterial nervous plexus, and the peritubular interstitium of the cortex and outer medulla. They were infrequent in central veins and the renal capsule and absent within glomeruli and the renal papilla. Ang II-positive fibers represented phenotypic subgroups of catecholaminergic postganglionic or sensory fibers with different morphology and intrarenal distribution compared to their Ang II-negative counterparts. The Ang II-positive postganglionic fibers were thicker, produced typically fusiform varicosities and preferentially innervated the outer medulla and periglomerular arterioles. Ang II-negative sensory fibers were highly varicose, prevailing in the pelvis and scarce in the renal periphery compared to the rarely varicose Ang II-positive fibers. Neurons within renal microganglia displayed angiotensinergic, cate-cholaminergic, or combined phenotypes. Our results suggest that autonomic fibers may be an independent source of intrarenal Ang II acting as a neuropeptide co-transmitter or neuromodulator. The angiotensinergic renal innervation may play a distinct role in the neuronal control of renal sodium reabsorption, vasomotion and renin secretion.
- PublicationOpen AccessClinicopathologic features of molecular subtypes of triple negative breast cancer based on immunohistochemical markers(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Choi, Junjeong; Jung, Woo-Hee; Koo, Ja SeungThis study was performed to identify molecular subtypes of triple negative breast carcinoma (TNBC) based on immunohistochemical markers. We prepared a tissue microarray from TNBC specimens of 122 patients and performed immunohistochemical staining for cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR), claudin 3, claudin 4, claudin 7, E-cadherin, androgen receptor (AR), and gammma-glutamyltransferase (GGT1). Based on immunoreactivity, tumors were classified into basal-like (CK5/6 positive and/or EGFR positive), molecular apocrine (AR positive and/or GGT1 positive), claudin low (claudin 3, claudin 4, claudin 7 negative and/or E-cadherin negative), mixed (tumors belonging to two or more subtypes), and null (tumors not matching any other subtypes). The TNBC specimens of 122 patients included 27 basal-like (22.1%), 28 claudin low (23.0%), 12 molecular apocrine (9.8%), 23 mixed (18.9%) and 32 null (26.2%) subtype tumors. The molecular apocrine subtype showed the highest percentage of apocrine differentiation and the lowest Ki-67 labeling index (p<0.001 and p=0.040, respectively). In univariate analysis, tumor cell discohesiveness was related with shorter disease free survival (DFS) and overall survival (OS) (p=0.005, and 0.002, respectively). In multivariate analysis, tumor cell discohesiveness was related with shorter OS and CK5/6 positivity (p=0.018), and claudin 7 positivity (p=0.019) was related with shorter DFS. In conclusion, using immunohistochemical staining for CK5/6, EGFR, claudin 3, claudin 4, claudin 7, E-cadherin, AR, and GGT1, we categorized TNBC into a basal-like subtype, a claudin low subtype, a molecular apocrine subtype, a mixed subtype showing characteristics of two different subtypes, and a null subtype not belonging to any of the subtypes identified.
- PublicationOpen AccessMelatonin-synthesizing enzymes and melatonin receptor in rat thyroid cells(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) García-Marín, Rocío; Miguel, de Miguel; Fernández-Santos, José Mª; Carrillo-Vico, Antonio; Utrilla, José Carmelo; Morillo-Bernal, Jesús; Díaz-Parrado, Eduardo; Rodríguez-Prieto, Ismael; Guerrero, Juan Miguel; Martín-Lacave, InésMelatonin is an indoleamine with a wide spectrum of biological activities other than transmitting photoperiod information, including antioxidant, oncostatic, anti-aging and immunomodulatory properties. Although melatonin is synthesized mainly in the pineal gland, other tissues have the same capacity. In the present study, we examined whether two key enzymes in melatonin biosynthesis, arylalkylamine Nacetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT) and its receptor MT1 are expressed in the two endocrine thyroid cells of the rat, follicular cells and C cells. Reverse transcriptase polymerase chain reaction analyses demonstrated that both AANAT and HIOMT mRNAs are expressed in the rat thyroid C-cells, and MT1 expression has been detected in C cells and follicular cells. Immunofluorescence revealed that AANAT protein is localized in C-cell cytoplasm, and MT1 protein in both cell populations. These findings demonstrate that the rat thyroid expresses AANAT, HIOMT, and its receptor MT1, showing that C cells are the main melatonin-synthesizing sites in the thyroid. This local C-cell-secreted melatonin may protect follicular cells from the oxidative stress inherent to the thyroid gland, and could also have paracrine and autocrine functions.
- PublicationOpen AccessDistribution of exogenous metallothionein following intraperitoneal and intramuscular injection of metallothionein-deficient mice(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Lewis, Katherine E. Lewis; Chung, Roger S.; West, Adrian K.; Chuah, Meng InnMetallothionein-I/II (MT-I/II) is a small metal-binding protein with antioxidant and neuroprotective properties, which has been used experimentally as a neurotherapeutic agent in multiple conditions. Therefore it is important to determine whether exogenous MT-I/II is retained in specific organs or expelled from the body following intramuscular and intraperitoneal injection. The distribution of exogenous MT-IIA (the major human MT-I/II isoform) was examined in MT-I/II-deficient mice, by immunohistochemistry of tissue samples and western blotting of urine samples. MT-IIA was detected within epithelial cells of the kidney cortical and medullary tubules within 1 hour of either intramuscular or intraperitoneal injection. Additionally, MT-IIA was detected within the urine at 1 hour after injection, indicating rapid absorbance into the circulation and filtration through the kidney glomerulus. A portion of the intramuscularly-injected MT-IIA remained within the muscle for at least 24 hours after injection. No MT-IIA was observed within the liver or the brain after either a single injection or a series of MT-IIA injections. These results are consistent with earlier reports that exogenously administered MT-IIA does not cross the intact blood-brain barrier, although a receptor for MT-I/II (megalin) is present in the choroid plexus. We postulate that due to losses through the urine, circulating MT-IIA levels drop rapidly after injection and do not permit transport across the choroid plexus. Peptide analogues of MT-I/II with similar neuroactive properties (emtins) may be more suited for CNS delivery.
- PublicationOpen AccessIQGAP1: A microtubule-microfilament scaffolding protein with multiple roles in nerve cell development and synaptic plasticity(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Jausoro, Ignacio; Mestres, Iván; Remedi, Mónica; Sanchez, Mónica; Cáceres, AlfredoIn this article, we review our current understanding of the biology of IQ domain-containing GTPase-Activating Protein 1, IQGAP1, a scaffolding protein with multiple binding partners, which is widely expressed among different cell types, including neurons, and capable of linking Rho-GTPase signaling with cytosleletal elements and environmental cues. Interestingly, a series of recent studies suggest that IQGAP family members have an important role in neuronal development, synaptic plasticity and nervo system disorders involving alterations in spine density.
- PublicationOpen AccessIdentification of S100A8 and S100A9 as negative regulators for lymph node metastasis of gastric adenocarcinoma(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Choi, Jin Hwa; Shin, Na Ri; Moon, Hyun Jung; Kwon, Chae Hwa; Kim, Gwang Ha; Song, Geun Am; Jeon, Tae Yong; Kim, Dae Hwan; Kim, Dong Hun; Park, Do YounWith increasing therapeutic use of minimally invasive therapy for treatment of early gastric cancer, prediction of lymph node metastasis is important. In search of tissue biomarkers for prediction of lymph node metastasis of gastric adenocarcinoma, we analyzed gastric adenocarcinoma tissue using proteomic methods. We have done 2D-PAGE and MALDI-TOF MS analysis in matched normal and gastric cancer tissues. We also evaluated the clinicopathological significance of expression of S100A8 and S100A9 in gastric adenocarcinoma using a tissue microarray of 218 gastric adenocarcinoma specimens. Cell invasion and migration assay were performed to confirm functional role of S100A8 and S100A9 using small hairpin RNA lentivirus. We identified 8 up-regulated and 5 down-regulated proteins in gastric cancer tissues compared to matched normal mucosa. Of these, expression of S100A8 and S100A9 occurred mainly in stromal cells and inflammatory cells between tumor cells. Correlation was observed between small lesion size, decreased depth of invasion, a tendency to absence of lymphovascular tumor emboli, a decrease in perineural invasion and lymph node metastasis, and expression of stromal S100A8. In addition, increased expression of stromal S100A9 in gastric adenocarcinoma was associated with small lesion size and a decrease in lymph node metastasis. Functional analysis confirmed that down-regulation of S100A8 and S100A9 by small hairpin RNA lentivirus induced an increase of migration and invasion in gastric cancer cell lines. Taken together, these findings suggest that S100A8 and S100A9 are negative regulators of lymph node metastasis of gastric adenocarcinoma and can be used as biomarkers for prediction of lymph node metastasis in gastric adenocarcinoma.
- PublicationOpen AccessExpression of matricellular proteins in human uterine leiomyomas and normal myometrium(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Bogusiewicz, Michal; Semczuk, Andrzej; Juszczak, Malgorzata; Langner, Ewa; Walczak, Katarzyna; Rzeski, Wojciech; Tomaszewski, Jacek; Rechberger, TomaszGrowth of human leiomyomas can probably be initiated as a response to injury, in a way similar to the development of keloids. Among many bioactive molecules, which are implicated in tissue repair, a pivotal role is attributed to matricellular proteins. The aim of the current study was to evaluate the immunohistochemical expression of tenascin-C (TNC), thrombospondin-1 (TSP-1), SPARC/osteonectin and tenascin-X (TNX) in human uterine leiomyomas and normal myometrium. Immunostaining was performed on 33 pairs of paraffin-fixed sections and 9 cell-lines derived from uterine leiomyomas and normal myometrium. Fifteen (45.5%) leiomyomas investigated were positive for TNC, whereas all normal myometrial samples were immunonegative (χ2=19.41; p<0.001). Immunostaining for TSP-1 was observed in 20 (60.6%) uterine fibroids and in 12 (36.4%) control samples (χ2=3.88; p<0.05). The expression of SPARC/osteonectin protein was more frequently found in leiomyomas than in normal myometrium, but this difference was not significant. Apart from one fibroid culture and one myometrial culture, all the others revealed strong TNC immunostaining. Expression of TSP-1 and SPARC/osteonectin was weak to moderate in all established cell-lines. None of the tissues or cell lines investigated showed positive staining for TNX. In conclusion, TSP-1 and TNC are likely to play important roles in the pathogenesis of uterine leiomyomas, presumably affecting cell proliferation and/or extracellular matrix deposition.