Histology and histopathology Vol.20, nº 4 (2005)

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Open Access
Ultrastructural changes in rat livers perfused in vitro and in vivo with a high dose of methotrexate
(Murcia : F. Hernández, 2005) Al-Ali, Saad Y.; Hassan, Ibrahim M.; Sadek, S.
Methotrexate is an antifolate that is widely used in the treatment of malignant tumours and other diseases. The present study was undertaken to examine the short-term effects of high doses of methotrexate (HD-MTX) on the ultrastructure and metabolic activity of isolated rat livers. The authenticity of the druginduced changes was substantiated by the concomitant use of in vivo experiments. Isolated rat livers were infused with HD-MTX via the portal vein for 3 hours (total dose for each liver 2000 mg). For in vivo experiments, each rat received a single intravenous injection of a maximum tolerated dose of MTX (100 mg/kg body weight) that allowed the animals to survive for 3 days. At the end of each experimental period, MTX-treated and control livers were processed for light microscopy (LM), scanning (SEM) and transmission electron (TEM) microscopy. Oxygen consumption and thyroxine metabolism were measured in treated and control isolated livers. With the exception of a few minor differences, the structural changes in the hepatocytes after MTX treatment in vitro and vivo were similar. There were focal changes consisting of disruption of normal hepatic plates and swelling and vacuolation of the hepatocytes, with no clear evidence of restriction to a specific hepatic zone. SEM revealed striking changes in the plasma membrane, the microvillar system, intercellular junctions and the sinusoidal endothelium. TEM revealed disorganized endoplasmic reticulum, dispersion of the polyribosomes, a variety of mitochondrial changes, and glycogen redistribution. In MTX-treated isolated rat livers, the uptake of tetraiodothyronine (T4) was not affected, but triiodothyronine (T3) release was impaired. Oxygen consumption was increased in livers treated with MTX. Employing an organotypic liver perfusion model in conjunction with the in vivo experiment and the use of SEM, TEM and hepatic thyroxine measurements, this investigation revealed that infusion of HD-MTX induced early ultrastructual changes in cell membrane, intercellular junctions and cell organelles and disturbance in the functional integrity of the hepatocytes in isolated rat liver.
Open Access
Cox and mesothelioma: an overview
(Murcia : F. Hernández, 2005) Cardillo, I.; Spugnini, E.P.; Verdina, A.; Galati, R.; Citro, G.; Baldi, A.
Cyclooxygenases catalyze the rate limiting step in the production of prostanoids. Accumulating data demonstrate that overexpression of these enzymes, and in particular of cyclooxygenases-2, promotes multiple events involved in tumorigenesis; in addition, numerous studies show that inhibition of cyclooxygenases-2 can delay or prevent certain forms of cancer. Malignant mesothelioma is a lethal pleural, peritoneal and pericardial neoplasia that actually lacks valid therapies and in which cyclooxygenases-2 is recognized as an important adverse prognostic factor. Hence, there is an increasing interest in the development of new treatments based on cyclooxygenases-2 inhibitors, to prolong survival and even potentially cure this neoplasia.
Open Access
Time course variations of antioxidant enzyme activities and histopathology of gilthead seabream gills exposed to malathion
(Murcia : F. Hernández, 2005) Rosety, M.A.; Rosety-Rodriguez, M.; Ordóñez Muñoz, F.J.; Rosety, I.
In a widely distributed and commercially important fish, gilthead seabream Sparus aurata L., we have studied sublethal effects of malathion in order to identify early warning bioindicators of exposure before irreversible damage occurs. To achieve this goal, groups of 10 juvenile specimens were exposed for 24, 48, 72 and 96h to a sublethal concentration of malathion (0.4 mg/l). Another group was used as control. The activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and histopathological features from exposed gills were assessed. It should also be mentioned that no mortality was observed during the whole experience. The activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) were altered significantly from 24 h onward (p<0.05). It is of interest to note that catalase activity was decreased after exposure instead of increasing as other antioxidant enzymes assessed. On the other hand, histopathological alterations of the gills were observed as early as at 48 hexposure, but the most severe damage occurred at 96 h exposure. The evidence presented here, together with other data from the literature, unequivocally established oxidative-stress-inducing effects of malathion in gilthead seabream Sparus aurata. It is also concluded antioxidants employed (SOD, CAT and GPX) changed significantly a long time before histopathological alterations of gills became evident. Consequently, these antioxidant enzymes may be highly recommended as early-warning bioindicators of environmental pollution by malathion in the areas where it is proposed to be used in pest control activities.
Open Access
Immunohistochemical and microscopic studies on giant cells in tuberous sclerosis
(Murcia : F. Hernández, 2005) Jozwiak, J.; Jozwiak, S.; Skopinski, P.
Tuberous sclerosis (TSC) is an autosomal dominant disease, caused by mutations in TSC1 or TSC2 genes, encoding hamartin and tuberin, respectively. The clinical picture of the disease is connected with the formation of hamartomas, mainly in the heart, kidneys and the brain. In three types of brain lesions: cortical tubers, subependymal nodules and subependymal giantcell astrocytoma (SEGA) characteristic, so-called “giant cells” are found. In the present review we summarise immunohistochemical findings of two types of studies performed on giant cells aiming at establishing the expression of hamartin and tuberin level and determining the presence of neuron- or astrocyte-specific markers. Moreover, we support our argument with the summary of ultrastructural research done with the purpose of demonstrating structures characteristic of neural and/or glial cells. We conclude that giant cells in cortical tubers and SEGAs are the same undifferentiated cells that, depending on individual determination, can show neural or glial features
Open Access
Tailgut cyst associated with a carcinoid tumor: case report and review of the literature
(Murcia : F. Hernández, 2005) Mathieu, A.; Chamlou, R.; Le Moine, F.; Maris, C.; Van de Stadt, J.; Salmon, I.
We report the case of a 49-year-old woman who presented a tailgut cyst lined by a variety of epithelium including squamous, columnar and transitional. Fortuitously a microscopic carcinoid tumor expressing immunohistochemically neuroendocrine markers was identified in the cystic wall. Tailgut cysts are congenital abnormalities located in the presacrococcygeal area occurring usually in adult patients. Clinical diagnosis is difficult because they are often asymptomatic. Patients may present symptoms resulting from local mass effects or complications. The differential diagnoses include rectal duplication cysts, cystic sacrococcygeal teratomas, epidermal cysts, epidermoid cysts, anal duct or gland cysts. Magnetic resonance imaging has recently become the modality of choice to image the cyst. Malignant transformation is rare; 23 cases including 10 carcinoid tumors have been reported in the literature. To our knowledge, this is the eleventh case of carcinoid tumor arising in a tailgut cyst.
Open Access
Comparative analysis of CD1a, S-100, CD83, and CD11c human dendritic cells in normal, premalignant, and malignant tissues
(Murcia : F. Hernández, 2005) Perez, L.; Shurin, M.R.; Kogan, D.; Tourkova, I.L.; Shurin, G.V.; Collins, B.
A number of antibodies that recognize human dendritic cells (DC) have been identified. The main aim of this study was to compare and contrast different antigen retrieval techniques using both enzymatic and non-enzymatic treatments in order to determine the expression and distribution of several DC markers on formalin-fixed, paraffin-embedded tissues. Normal human lung, oral epithelial hyperplasia lesions, oral squamous cell carcinoma, and prostate adenocarcinoma tissues were evaluated using a panel of DC specific antibodies. The results of immunohistochemical staining for CD83, CD1a, CD11c, and S-100 DC markers were compared following the different antigen retrieval approaches. The overall best results for the analysis of tumor-associated DC were obtained with the enzymatic methods. Protease XXIV digestion was determined to be essential for detection of S-100 and CD11c positive DC, whereas trypsin and pepsin were required for the recognition of CD1a and CD83 expressing tumor-associated DC. These results could be easily adapted for routine practice and should be useful for characterization of the DC system in cancer patients for both diagnostic and prognostic purposes. In addition, standardized procedures for evaluating different subpopulations of tumor-associated DC should bring new insights in understanding of DC-tumor cell interaction.
Open Access
Embryonic development of the bovine pineal gland (Bos taurus) during prenatal life (30 to 135 days of gestation)
(Murcia : F. Hernández, 2005) Regodón, S.; Roncero, V.
The ontogenesis of the pineal gland of 30 bovine embryos (Bos taurus) has been analysed from 30 until 135 days of gestation by means of optical microscopy and immunohistochemical techniques. For this study, the specimens were grouped into three stages in accordance with the most relevant histological characteristics: Stage 1 (30 to 64 days of prenatal development); Stage 2 (70 to 90 days) and Stage 3 (106 to 135 days). In the cow, it is from 30 days of gestation that the first glandular outline becomes differentiated from the diencephalic ependyma of the third ventricle. This differentiation includes the phenomena of proliferation and multiplication of the ependymal cells that form the epithelium of the pineal outline in development. At 82 days of intrauterine life, in the interior of the pineal parenchyma, we witnessed some incipient pseudoglandular structures that at 135 days were well differentiated. The pineal parenchyma displays a cytology made up of two cellular types of structurally distinct characteristics: pinealoblasts and interstitial cells. Both cellular types begin differentiation at 70 days of embryonic development, the pinealoblasts being greater in number than the interstitial cells. The glandular stroma is formed from the capsular, trabecular and the perivascular connective tissue, filling the interparenchymal space. A dense network of capillaries, which drive across the trabecular connective tissue towards the central glandular zone where their density increases and their calibre is reduced, complete the glandular structure. GFAP positive cells were observed in the embryonic pineal parenchyma in stage 3. At 135 days of gestation, NPY positive fibers entered the pineal gland through the pineal capsule occupying a perivascular localization. Morphological studies of this nature are vital for future use as parameters, indicative of the functional activity of the bovine pineal gland during embryonic development.
Open Access
The role of fetal breathing-like movements in lung organogenesis
(Murcia : F. Hernández, 2005) Inanlou, M.R.; Baguma-Nibasheka, M.; Kablar, B.
In this review the recent findings concerning the role of fetal breathing-like movements (FBMs) on lung organogenesis are discussed. We first review the consequences that the lack of FBMs has on lung organogenesis and then we discuss the possible pathways that may be employed in this process. Specifically, we review the data in support of the notion that FBMs are required for the cell cycle kinetics regulation (i.e., cell proliferation and cell death) via the expression of growth factors, such as platelet derived growth factors (PDGFs) and insulin growth factors (IGFs), and thyroid transcription factor 1 (TTF-1). Moreover, the role of FBMs on biochemical differentiation of Clara cells, type I and type II pneumocytes is reviewed. Interestingly, even though type II pneumocytes are able to synthesize surfactantassociated proteins (SPs), in the complete absence of FBMs, they are unable to compile, store and release the surfactant. Similarly, in spite of the expression of some early differentiation markers, in the absence of FBMs, type I pneumocytes are unable to flatten in order to allow the gas exchange in the lung. In fact, we are currently employing the cDNA microarray analysis in search for the molecules that might be specific for the lacking functions in pneumocytes. Key words: Lung hypoplasia, Mouse embry
Open Access
DEC1 expression in 1p-aberrant oligodendroglial neoplasms
(Murcia : F. Hernández, 2005) Preusser, Matthias; Birner, P.; Ambros, I.M.; Ambros, P.F.; Budka, H.; Harris, A.L.; Hainfellner, J.A.
Background. Expression of hypoxia-related tissue factors in 1p-aberrant oligodendroglial neoplasms diminishes patient outcome. Differentiated embryochondrocyte expressed gene 1 (DEC1) has been described as novel hypoxia-related tissue factor. In our study, we assessed the expression of DEC1 in 1p aberrant oligodendroglial neoplasms and its association with necrosis and expression of hypoxia-inducible factor 1a (HIF-1a), carbonic anhydrase-9 (CA9), and vascular endothelial growth factor-mRNA (VEGF). Materials and methods. 44 primary and 16 recurrent oligodendroglial neoplasms with 1p-aberrations were investigated immunohistochemically for the expression of DEC1, HIF-1a, and CA9. Expression of VEGF was investigated using in situ hybridization. DEC1 expression was correlated with necrosis and with expression of HIF-1a, CA9, and VEGF. Results. DEC1 was expressed in tumor cell nuclei, and occasionally in nuclei of endothelial cells, and glial and neuronal cells of surrounding brain tissue. High expression (>10% of tumor cells immunolabeled) of DEC1 was found in 56 cases, low expression (<10% of tumor cells immunolabeled) was found in 3 cases. In 1 case no expression of DEC1 was evident. DEC1 expression showed no topographical association with necrosis or expression of HIF-1a, CA9, or VEGF. Conclusion. DEC1 expression is found in the majority of 1p-aberrant oligodendroglial neoplasms and does not correlate with necrosis or expression of HIF-1a, CA9, VEGF. Thus, immunohistochemical analysis of DEC1 expression is in our hands not suitable for detection of tissue hypoxia in this type of primary brain tumor.
Open Access
Differential expression of prostaglandin E receptor subtype EP2 in rat uterus during early pregnancy
(Murcia : F. Hernández, 2005) Shi, J.J.; Ma, X.H.; Diao, H.L.; Ni, H.; Xu, L.B.; Zhu, H.; Yang, Z.M.
PGE2 is essential for mammalian female reproduction. This study was to examine the expression of EP2 gene in the rat uterus during early pregnancy, delayed implantation and artificial decidualization by in situ hybridization and immunohistochemistry. There was no detectable EP2 mRNA expression in the uterus from days 1 to 4 of pregnancy (day 1 = day of vaginal sperm). A low level of EP2 immunostaining was observed in the luminal and glandular epithelium from days 1 to 4 of pregnancy. Both EP2 mRNA and protein expression were highly detected in the luminal epithelium at implantation sites on day 6 of pregnancy. EP2 expression decreased from day 7 of pregnancy and was undetectable on days 8 and 9 of pregnancy. After delayed implantation was terminated by estrogen treatment and the embryo implanted, both EP2 mRNA and protein expression were strongly observed in the luminal epithelium at the implantation site. There was no detectable EP2 expression in both control and decidualized uteri. In conclusion, these data suggest that EP2 expression at implantation site may play an important role during embryo implantation in rats.
Open Access
Anagrelide does not exert a myelodysplastic effect on megakaryopoiesis: a comparative immunohistochemical and morphometric study with hydroxyurea
(Murcia : F. Hernández, 2005) Thiele, J.; Kvasnicka, H.M.; Ollig, S.; Schmitt-Gräff, A.
A comparative immunohistochemical and morphometric study was performed on megakaryocytes in 20 patients presenting with initial-early stage chronic idiopathic myelofibrosis and accompanying thrombocythemia to elucidate histological features developing after hydroxyurea (HU) versus anagrelide (ANA) therapy. Representative pre-and posttreatment bone marrow biopsies were involved including the monoclonal antibody CD61 for the identification of precursor and mature stages of megakaryopoiesis. An elaborate morphometric evaluation was in keeping with a left-shifting showing a more frequent occurrence of promegakaryoblasts and microforms in both therapy groups. However, contrasting ANA, HU generated defects of differentiation consistent with significant dysplastic changes. In conclusion, concern about a possible leukemogenic capacity following long-term HU therapy is supported by our findings.
Open Access
The effect of the flavonoid diosmin, grape seed extract and red wine on the pulmonary metastatic B16F10 melanoma
(Murcia : F. Hernández, 2005) Martínez, C.; Vicente García, Vicente; Yáñez, J.; Alcaraz, M.; Canteras, M.; Benavente-García García, Obdulio; Castillo, J.; Castells Mora, María Teresa
Objective: To study the effect of different phenolic compounds and red wine on pulmonary metastatic melanoma. Methods: Swiss mice were inoculated with 5x105 melanocytes B16F10 and given oral doses of diosmin, grape seed extract (GSE) and red wine. A macroscopic count was made of the metastatic nodules on the lung surface and a microscopic study by image analysis of five sections, calculating the implantation percentage and tumoral growth and invasion indices. Results: Macroscopically, the group treated with diosmin showed the greatest reduction (52%) in the number of metastatic nodules compared with the control group, which was treated with ethanol, while GSE and red wine caused decreases of 26.07 and 28.81%, respectively. Microscopically, there was a decrease in the implantation percentage after the administration of diosmin (79.4%) and red wine (20.19%), and an increase of 2.12% after the administration of GSE, all relative to the ethanol-treated control. As regards the growth index, diosmin produced a reduction of 67.44% and red wine a reduction of 20.62%, while GSE again produced an increase (25.33%). The reductions in the invasion index were 45.23, 31.65 and 17.57% with diosmin, GSE and red wine, respectively. Conclusions: Diosmin originated the greatest reduction in pulmonary metastases, both at the macroscopic and microscopic levels.
Open Access
Is mitotic chromatid segregation random?
(Murcia : F. Hernández, 2005) Bell, C.D.
The question of whether mitotic segregation of chromatids is random or programmed assumes great significance for cellular differentiation if one recognizes that sister chromatids may have epigenetic differences and carry them from one generation into the next. The literature was examined for evidence of nonrandom chromosomal and chromatid segregation. Many organisms were described as undergoing non-random homologue segregation in meiosis I. The explanations for these phenomena were attributed in some instances, to peculiarities of the meiotic spindle, though in some convincing experiments, the epigenetic heterochromatin of the kinetochores was implicated. The few existing descriptions of non-random mitotic segregation were also described. Existing literature on ultrastructural, immunohistochemical, and physiological features of the chromatid kinetochores during the mitotic process was searched for evidence of asymmetry or structural differences between sister chromatids, which is presented. Also reported are descriptions of how epigenetic changes and cell differentiation can influence centromeric function and ultimately, kinetochore function. Fundamental to the hypothesis of gene regulation presented here, is the assumption that genetic foci on different chromosomes interact, and must be proximate to each other and stereologically compatible for interactions to occur. Also described are spatial changes in chromosomal territories associated with function and differentiation. These territories can be in varying nuclear locations depending on gene function, and may show asymmetry between daughter cells. Despite evidence presented for the possibility of non-random chromatid segregation at mitosis, this question will remain unanswered until the matter is specifically addressed by experiment.
Open Access
Hypoxia inducible factor-1 and facilitative glucose transporters GLUT1 and GLUT3: Putative molecular components of the oxygen and glucose sensing apparatus in articular chondrocytes
(Murcia : F. Hernández, 2005) Mobasheri, A.; Richardson, S.; Mobasheri, R.; Shakibaei, M.; Hoyland, J.A.
Articular cartilage is an avascular connective tissue in which the availability of oxygen and glucose is significantly lower than synovial fluid and plasma. Glucose is an important metabolic fuel and structural precursor that plays a key role in the synthesis of extracellular matrix macromolecules in articular cartilage. However, glucose concentrations in cartilage can fluctuate depending on age, physical activity and endocrine status. Chondrocytes are glycolytic cells and must be able to sense the quantities of oxygen and glucose available to them in the extracellular matrix and respond appropriately by adjusting cellular metabolism. Consequently chondrocytes must have the capacity to survive in an extracellular matrix with limited nutrients and low oxygen tensions. The molecular mechanisms responsible for allowing chondrocytes to adapt to these harsh environmental conditions are poorly understood. In this article we present a novel “dual” model of oxygen and glucose sensing in chondrocytes based on recent experimental data. This model incorporates the hypoxiainducible factor alpha (HIF-1a) as an oxygen sensor and the hypoxia responsive facilitative glucose transporters, GLUT1 and GLUT3 as putative components of the glucose sensing apparatus in chondrocytes. Recent studies have shown that GLUT1 and GLUT3 are both expressed in chondrocytes and their HIF-1a-mediated transcription may be dually stimulated in response to hypoxia and low glucose conditions which in turn promote anaerobic glycolysis in favor of oxidative phosphorylation. This working model provides, for the first time, a unifying hypothesis to explain how chondrocytes might sense and respond to low oxygen tensions and alterations in extracellular glucose.
Open Access
Nestin expression in normal adrenal gland and adrenocortical tumors
(Murcia : F. Hernández, 2005) Toti, P.; Regoli, M.; Nesi, G.; Occhini, R.; Bartolommei, S.; Fonzi, L.; Bertelli, E.
Human adrenocortical cells have been shown to express cytokeratins and vimentin. Nestin is an intermediate filament protein that is mainly expressed in the developing nervous system and that has been recently reported in rat adrenal gland as well. Using immunohistochemical and biochemical approaches, the present study demonstrates that nestin is constantly expressed in situ in the cortex of normal human adrenal glands. Nestin expressing cells were prevalently located in the zona reticularis but some positive cells could be spotted in the zona fasciculata as well. Moreover, patches of nestin-positive cells have been constantly detected on sections of cortical adenomas. In contrast, adrenal carcinomas displayed a variable number of nestin-immunoreactive cells that in some cases were virtually absent. Samples of renal clear cell carcinoma metastasis in the adrenals were also examined which did not show nestin-immunoreactivity. We propose that a positive nestin-immunoreaction could be useful in differential diagnosis of clear cell tumors in adrenal glands.
Open Access
The role of the bone marrow microenvironment in multiple myeloma
(Murcia : F. Hernández, 2005) De Raeve, H.; Vanderkerken, K.
Multiple myeloma (MM) is a malignant disease that results from an excess of monotypic plasma cells in the bone marrow (BM). This malignancy is characterised by complex karyotypic aberrancies. In 60% of all MM there are recurrent primary translocations involving the heavy chain gene locus. The MM cells strongly interact with the BM microenvironment, which is composed of endothelial cells, stromal cells, osteoclasts, osteoblasts, immune cells, fat cells and the extracellular matrix. This interaction is responsible for the specific homing in the BM, the proliferation and survival of the MM cells, the resistance of MM cells to chemotherapy, the development of osteolysis, immunodeficiency and anaemia. New therapeutic agents target both the MM, as well as the interaction MM cell – BM microenviroment.
Open Access
Ontogeny of the antigen-reactive lymph follicle-forming capacity of the popliteal lymph node in neonatal mice
(Murcia : F. Hernández, 2005) Hiramoto, M.; Aizawa, S.; Horie, K.; Nagata, H.; Hoshi, H.
The ontogenetic development of the reactive lymph follicle-forming capacity of the popliteal lymph node was investigated immunohistochemically in young mice which had received a single injection of hemocyanin (KLH) in a rear footpad at a predetermined age (between 1 and 21 days). The mice were sacrificed at various intervals after injection. In non-stimulated young mice, primary lymph follicles first appeared in the popliteal node at 11 days of age. When KLH was given to 7-day-old or older mice, each draining popliteal node showed a marked increase in B lymphocytes in the extrafollicular zone 3 days after injection and produced a number of ‘new’ lymph follicles outside the pre-existing follicles over the next few days. In mice injected at 2-4 days of age, these nodes showed an increase in B lymphocytes in the outer cortex and had produced several lymph follicles by 8 days of age. The number of lymph follicles produced by each node tended to increase in line with age at injection. These results indicate that neonatal popliteal nodes become able to produce lymph follicles in response to exogenous antigens some time before ontogenetically developing follicles appear. The formation of new lymph follicles observed in draining popliteal nodes after KLH injection at an early postnatal age is discussed in relation to the ontogenetic development of stromal cells (precursors of follicular dendritic cells) that are capable of interacting with B lymphocytes and the extent of B lymphocyte influx into the node induced by KLH stimulation.
Open Access
Hepatocyte growth factor/scatter factor and prostate cancer: a review
(Murcia : F. Hernández, 2005) Hurle, R.A.; Davies, Graham; Parr, C.; Mason, M.D.; Jenkins, S.A.; Kynaston, H.G.; Jiang, W.G.
Men who die from prostate cancer do so from uncontrolled metastatic disease. A better understanding of the mechanisms involved in the progression and metastasis of prostate cancer may lead to novel therapeutic approaches to prevent its natural progression. Hepatocyte Growth Factor / Scatter factor (HGF/SF) has been demonstrated to elicit a number of key functions in numerous tissues that are important in the progression, invasion and metastasis of cancer. Studies have demonstrated that the activity of HGF/SF and its receptor c-Met are linked to disease progression in numerous cancers. However, research into these functions, which include activities as a mitogen, a motogen and an anti-apoptotic and angiogenic factor in prostate cancer are limited. This article reviews the published evidence of the roles HGF/SF plays in prostate cancer progression and highlights the clinical and therapeutic potential of research into this pleiomorphic cytokine.
Open Access
Human galectin-2: expression profiling by RT-PCR/immunohistochemistry and its introduction as a histochemical tool for ligand localization
(Murcia : F. Hernández, 2005) Saal, I.; Nagy, N.; Lensch, M.; Lohr, M.; Manning, J.C.; Decaestecker, C.; André, S.; Kiss, R.; Salmon, I.; Gabius, H.J.
Sugar-encoded information of glycoconjugates is translated into cellular responses by endogenous lectins. Galectins stand out against other lectin families due to their wide range of functions including cell adhesion, tissue invasion or growth regulation exerted at extracellular, membrane, cytoplasmic and nuclear sites. This remarkable versatility warrants close scrutiny of their emerging network, in this study with focus on homodimeric human galectin-2. We first detected presence of specific mRNA in various tissue types by processing post mortem and surgical specimens by RT-PCR protocols. Overlap of gene expression was noted with proto-type galectins-1 and -7 and also family members from the other two subgroups. To monitor expression on the level of protein a polyclonal anti-galectin-2 antibody was raised. Immunopositivity was semi-quantitatively assessed in sections of 209 human samples establishing an array both of normal tissues and samples with inflammation or benign/malignant growth. In general, positivity was predominantly epithelial without restriction of staining to certain tissue types, as fittingly indicated by our RT-PCR analysis. Staining was not limited to the cytoplasm but also included nuclear sites. To examine the suitability of the labeled lectin as a histochemical probe we biotinylated galectin-2 under activity-preserving conditions and introduced it to tissue profiling. Specific cytoplasmic staining proved the validity of the concept. Our results encourage systematic histopathologic studies by immuno- and lectin histochemistry, especially by adding galectin-2 as study object to galectin fingerprinting which has already yielded prognostic information on galectins-1, -3, -4 and -8 and hereby contributed to define functional overlap/divergence in this lectin family.
Open Access
Nuclear phosphoinositide specific phospholipase C (PI-PLC)-ß1: a central intermediary in nuclear lipid-dependent signal transduction
(Murcia : F. Hernández, 2005) Martelli, A.M.; Fiume, R.; Faenza, I.; Tabellini, G.; Evangelisti, C.; Bortul, R.; Follo, M.Y.; Falà, F.; Cocco, L.
Several studies have demonstrated the existence of an autonomous intranuclear phosphoinositide cycle that involves the activation of nuclear PIPLC and the generation of diacylglycerol (DG) within the nucleus. Although several distinct isozymes of PIPLC have been detected in the nucleus, the isoform that has been most consistently highlighted as being nuclear is PI-PLC-ß1. Nuclear PI-PLC-ß1 has been linked with either cell proliferation or differentiation. Remarkably, the activation mechanism of nuclear PI-PLC-ß1 has been shown to be different from its plasma membrane counterpart, being dependent on phosphorylation effected by p44/42 mitogen activated protein (MAP) kinase. In this review, we report the most up-dated findings about nuclear PI-PLC-ß1, such as the localization in nuclear speckles, the activity changes during the cell cycle phases, and the possible involvement in the progression of myelodisplastic syndrome to acute myeloid leukemia.