Histology and histopathology Vol.16, nº 1 (2001)

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Open Access
Detection of altered retinoic acid receptor expression in tissue sections using in situ hybridization
(Murcia : F. Hernández, 2001) Xu, X.C.
Nuclear retinoid receptors mediate retinoid effects in controlling cell growth, differentiation, apoptosis, and carcinogenesis. Altered expression or activity of these receptors could abolish the retinoid signal transduction pathway and be associated with human carcinogenesis. In situ hybridization is a powerful tool for analyzing gene expression in formalinfixed, paraffin-embedded tissue sections, especially for newly cloned genes or when no antibodies are available. Detection of altered retinoid receptor expression using in situ hybridization in premalignant and malignant tissues has provided important information about the roles of these receptors in cancer development and the response of these tissues to retinoid treatment. Among these receptors, altered expression of retinoic acid receptor-B (RAR-B) has been mostly detected in human cancers, including those of the head and neck, lung, esophagus, mammary gland, pancreas, and cervix. RAR-B is thus currently used as a surrogate endpoint biomarker in different clinical prevention trials of various cancers
Open Access
TIMP-1 promotes VEGF-induced neovascularization in the retina
(Murcia : F. Hernández, 2001) Yamada, E.; Tobe, T.; Yamada, H.; Okamoto, N.; Zack, D.J.; Werb, Z.; Soloway, P.D.; Campochiaro, P.A.
Proteolysis of vascular basement membranes and surrounding extracellular matrix is a critica1 early step in neovascularization. It requires alteration of the balance between matrix metalloproteinases (MMPs) and proteins that bind to and inactivate MMPs, tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 has been demonstrated to inhibit neovascularization in chick chorioallantoic membranes. However, TIMP-1 has also been shown to either promote or inhibit cell proliferation and migration in different settings. To determine whether genetic alteration of the MMPDIMP-1 ratio would alter retinal neovascularization, we crossed mice that express vascular endothelial growth factor (VEGF) in photoreceptors with TIMP-1-deficient mice or mice that overexpress TIMP-1. Compared to VEGF transgenepositive/ TIMP-1-sufficient mice, VEGF transgenepositive1TIMP- 1-deficient mice showed smaller neovascular lesions. There was also no difference between the two groups of mice in the appearance of the neovascularization by light or electron microscopy. Compound VEGFITIMP-1 transgenic mice had increased expression of both VEGF and TIMP-1 in the retina, and had more neovascularization than mice that had increased expression of VEGF alone. These gainand loss-of-function data suggest that alteration of the TIMP-1MMP ratio modulates retinal neovascularization in a complex manner and not simply by altering the proteolytic activity and thereby invasiveness of endothelial cells.
Open Access
Myenteric plexus of obese diabetic mice (an animal model of human type 2 diabetes)
(Murcia : F. Hernández, 2001) Spangeus, A.; El-Salhy, M.
The myenteric plexus of the gastrointestinal tract was investigated in the obese diabetic mouse, an animal model of human type 2 diabetes. Sections were immunostained by the avidin-biotin complex method, using a general nerve marker, protein gene product 9.5 (PGP 9.5), as well as antibodies to several important neurotransmitters. Computerized image analysis was used for quantification. When diabetic mice were compared with controls, no difference was found in the density of PGP 9.5-immunoreactive (IR) nerve fibres in antrum, duodenum or colon. In antrum and duodenum, diabetic mice showed a decreased number of vasoactive intestinal peptide (V1P)-IR neurons in myenteric ganglia as well a decreased relative volume density in myenteric plexus (though not significantly in antrum, p=0.073). No difference was found regarding VIP-IR nerves in colon. The volume density of nitric oxide synthase (NOS)-IR nerve fibres was decreased in antrum and duodenum of diabetic mice, whereas no difference was found in colon. The density of galanin-IR neme fibres was decreased in duodenum. Whereas neuropeptide Y (NPY)- and vesicular acetylcholine transporter (VAChT)-IR nerve fibres was increased in density in colon of diabetic mice, no difference was found in antrum and duodenum. Regarding substance P, there was no difference between diabetic and control mice in antrum, duodenum or colon. The present study shows that gut innervation is affected in this animal model of human type 2 diabetes. It is possible that the present findings may have some relevance for the gastrointestinal dysfunctions seen in patients with type 2 diabetes.
Open Access
Effect of endurance running on cardiac and skeletal muscle in rats
(Murcia : F. Hernández, 2001) Díaz-Herrera, P.; Torres, A.; Morcuende, J.A.; Garcia-Castellano, J.M.; Calbet, J.A.L.; Sarrat, R.
We studied the effect of resistance running on left cardiac ventricle size and rectus femoris muscle fiber composition. Ten male Wistar rats were trained on a treadmill 6 days per week for 12 weeks. Ten rats remained sedentary and served as controls. A higher endurance time (40%) and cardiac hypertrophy in the trained animals were indicators of training efficiency. Morphometric analysis of the left ventricle crosssectional area, left ventricular wall, and left ventricular cavity were evaluated. The endurance-running group demonstrated a hypertrophy of the ventricular wall (22%) and an increase in the ventricular cavity (25%); (pc0.0001). Semi-quantitative analysis of rectus femoris fiber-type composition and of the oxidative and glycolytic capacity was histochemically performed. Endurance running demonstrated a significant (pc0.01) increase in the relative frequency of 5 p e 1 (24%), Qpe IIA (8%) and 5 p e IIX (16%) oxidative fibers, and a decrease in Qpe IIB (20%) glycolytic fibers. There was a hypertrophy of both oxidative and glycolytic fiber types. The relative cross-sectional area analysis demonstrated an increase in oxidative fibers and a decrease in glycolytic fibers (p<0.0001). Changes were especially evident for 'Qpe IIX oxidative-glycolytic fibers. The results of this study indicate that the left ventricle adapts to endurance running by increasing wall thickness and enlargement of the ventricular cavity. Skeletal muscle adapts to training by increasing oxidative fiber 'Qpe. This increase may be related to fiber transformation from Qpe IIB glycolytic to Qpe IIX oxidative fibers. These results open the possibility for the use of this type of exercise to prevent muscular atrophy associated with age or post-immobilization.
Open Access
Glomerular profile numerical density per area and mean glomerular volume in rats submitted to nitric oxide synthase blockade
(Murcia : F. Hernández, 2001) Pereira, L.M.M.; Mandarim-de-Lacerda, Carlos A.
Rats submitted to chronic inhibition of nitric oxide synthase (NOS) have developed systemic hypertension and consequent renal injury. The present study aims to determine glomerular quantitative changes due to NOS inhibition in rats. Adults and normotensive Wistar rats were separated into control and L-NAME groups (each group n=10). The animals received water and food ad libitum, while L-NAME rats received N ~ - Nitro-L-Arginine methyl Ester hydrochloride to inhibit NOS (50mg/kg/day) in drinking water during 40 days. After that period the rats were sacrificed, the kidneys were removed, measured, and prepared for histological and stereological analyses. The glomerular density per area [NA(giom)] and the mean glomerular volume [Y] were determined per animal in 15 random fields. In LNAME rat the blood pressure was 76% higher than the respective control group with the same age. Glomeruli had global or segmental glomerular sclerosis; some glomeruli only presented an atrophic structure. The renal volume was not different between control and L-NAME rats (p>0.05). However, L-NAME rats had the NA(giom) 33% smaller than the control rats (p=0.0001) and, concomitantly, L-NAME rats had the Y (glom) 33% higher than the control ones (p=0.004). These results demonstrate morphological renal alterations caused by NOS inhibition and hypertension.
Open Access
Farnesyltransferase inhibitors define a role for RhoB in controlling neoplastic pathophysiology
(Murcia : F. Hernández, 2001) Prendergast, G.C.
A long-standing goal in cancer research is to identify cellular functions that have selective roles in regulating neoplastic pathophysiology. Farnesyltransferase inhibitors (FTIs) are a novel class of cancer chemotherapeutics which have little effect on normal cell physiology but which inhibit or reverse malignant cell phenotypes. FTIs were originally developed as a strategy to inhibit oncogenic Ras, the activity of which depends upon posttranslational farnesylation. However, recent work indicates the antineoplastic effects of FTIs are not linked to Ras inhibition but instead to alteration of RhoB, a small GTPase of the Rho family of cytoskeletal regulators that controls trafficking of cell surface receptors. Rho proteins integrate signals from integrins and cytokine receptors with cell shape via the actin cytoskeleton. A connection between FTIs and Rho alteration is interesting given that histological differences have long been used to define clinical cancer. RhoB is dispensable for normal cell growth and differentiation in mice. Thus, research into the antineoplastic effects of FTIs has led to the identification of a function(s) that is unnecessary for normal cell physiology but crucial for controlling malignant phenotypes.
Open Access
Immunohistochemical expression of p53 in animal tumors: a methodological study using four anti-human p53 antibodies
(2001) Albaric, O.; Bret, L.; Amardeihl, M.; Delverdier, M.
Mutations in the p53 tumor suppressor gene are the most common genetic alterations in human cancers. These mutations usually lead to strongly enhanced protein stabilization and allow detection by immunohistochemistry. Two monoclonal (DO-7 and PAb-240) and two polyclonal (Ab-7 and CM-l) antibodies were evaluated by standard immunoperoxidase method in domestic animal tumors, chiefly squamous cell carcinomas (Scq, and osteosarcomas as positive controls. Immunoreactivity was detected in SCC of cattle, sheep, horse and cat as well as in feline actinic keratosis, with PAb-240 and CM-l antibodies. One polyclonal antibody (Ab-7) did not give positive result at all, whereas DO-7 monoclonal antibody did not react in dogs and cats. Immunodetection of p53 protein is thus possible in all domestic species tested, especially with CM-l and PAb-240 antibodies, and p53 alterations seem to occur early in carcinogenesis of feli ne SCC as in comparable human lesions.
Open Access
Ultrastructural evidence in vitro of osteoclast-induced degradation of calcium phosphate ceramic by simultaneous resorption and phagocytosis mechanisms
(Murcia : F. Hernández, 2001) Heymann, D.; Guicheux, J.; Rousselle, A.V.
Osteoclasts are physiological polykaryons specialized in the resorption of calcified tissue. In the context of the clinical use of calcium-phosphate (Cap) ceramics as bone substitutes, this study used transmission electron microscopy to investigate the in vitro mechanisms of Cap ceramic degradation by osteoclastic cell types. Osteoclasts cultured on Cap ceramic developed typical ultrastructural features of bone osteoclasts, such as a polarized dome shape, a clear zone and a ruffled border. Modification of the shape and density of Cap crystals under the ruffled border indicated an acidic microenvironment. Moreover, osteoclasts were able to degrade ceramic by simultaneous resorption and phagocytosis mechanisms. Phagocytosis did not alter the ability of osteoclasts to resorb Cap ceramic. The phagocytosis mechanism consisted of three steps: crystal phagocytosis, disappearance of the endophagosome envelope membrane and fragmentation of phagocytosed crystals within the cytoplasm. The common mechanism of phagocytosis described here is similar to that observed with the monocyte/macrophage lineage, confirming that osteoclasts are part of the mononuclear phagocyte system. Osteoclasts are thus clearly involved in Cap degradation by means of resorption and phagocytosis
Open Access
Hepatocyte growth factor activators, inhibitors and antagonists and their implication in cancer intervention
(Murcia : F. Hernández, 2001) Parr, C.; Jiang, W.G.
Hepatocyte growth factor (HGF), otherwise known as scatter factor (SF), has been demonstrated over the past decade to elicit a number of functions that may be tumorigenic, and enhance the invasive/metastatic nature of cancer cells. Clinical studies have also demonstrated that HGFJSF, together with its receptor, cMET, is closely related to the disease progression and prognosis of patients with cancer. The past few years have seen the identification of numerous inhibitors and antagonists to the action of HGFISF. These factors have demonstrated a possible role in minimising the action of HGFISF on cancer cells, and may be of therapeutic value in the future. This article overviews the activators, inhibitors, and antagonists to HGFISF and discusses the possible implications in cancer therapy.
Open Access
Molecular medicine of TFF-peptides: from gut to brain
(Murcia : F. Hernández, 2001) Hoffmann, W.; Jagla, W.; Wiede, A.
TFF-peptides (Le. TFF1, TFF2, TFF3; formerly P-domain peptides, trefoil factors) have been established as secretory products typical of the gastrointestinal tract. Their synthesis has recently been recognized in a number of mucin-producing epithelial cells, for example, of the respiratory tract, the salivary glands, the uterus and of the conjunctiva. They have a pivotal role in maintaining the surface integrity of these delicate epithelia as constituents of mucus gels as well as by their anti-apoptotic properties and their motogenic activity modulating cell migratory processes. The latter is important for rapid healing in particular of gastrointestinal and respiratory epithelia by a process termed "restitution". On the other hand, one of these peptides - namely TFF3 - has been detected as a new neuropeptide of the human hypothalamo-pituitary axis where it is synthesized in oxytocinergic neurons of the paraventricular and supraoptic nuclei. From there it is transported to the posterior pituitary where it is released into the blood stream. Synthesis of TFF-peptides also occurs pathologically as result to chronic infiammatory diseases, for example of the gastrointestinal tract. Aberrant synthesis of TFF-peptides is observed in many tumors.
Open Access
Pax genes in development and maturation of the vertebrate visual system: Implications for optic nerve regeneration
(Murcia : F. Hernández, 2001) Ziman, M.R.; Rodger, J.; Chen, P.; Papadimitriou, J.M.; Dunlop, S.A.; Beazley, L.D.
Pax genes play a pivotal role in development of the vertebrate visual system. Paxó is the master control gene for eye development: ectopic expression of Paxó in Xenopus laevis and Drosphila melanogaster leads to the formation of differentiated eyes on the legs or wings. Paxó is involved in formation of ganglion cells of the retina, as well as cells of the lens, iris and cornea. In addition Pax6 may play a role in axon guidance in the visual system. Pax2 regulates differentiation of the optic disk through which retinal ganglion cell axons exit the eye. Furthermore, Pax2 plays a critical role in development of the optic chiasm and in the guidance of axons along the contralateral or ipsilateral tracts of the optic nerve to visual targets in the brain. During development Pax7 is expressed in neurona1 cells of one of the major visual targets in the brain, the optic tectumlsuperior colliculus. Neurons expressing Pax7 migrate towards the pia and concentrate in the stratum griseum superficiale (SGFS), the target site for retinal axons. Together, expression of Pax2, 6 and 7 may guide axons during formation of functional retinotectal/ collicular projections. Highly regulated Pax gene expression is also observed in mature animals. Moreover, evidence suggests that Pax genes are important for regeneration of the visual system. We are currently investigating Pax gene expression in species that display a range of outcomes of optic nerve regeneration. We predict that such information will provide valuable insights for the induction of successful regeneration of the optic nerve and of other regions of the central nervous system in mammals including man.
Open Access
Isoforms of Na+, K+-ATPase in human prostate; specificity of expression and apical membrane polarization
(Murcia : F. Hernández, 2001) Mobasheri, A.; Oukrif, D.; Dawodu, S.P.; Sinha, M.; Greenwell, P.; Stewart, D.; Djamgoz, M.B.A.; Foster, C.S.; Martín-Vasallo, P.; Mobasheri, R.
The cellular distribution of Na+, K+-ATPase subunit isoforms was mapped in the secretory epithelium of the human prostate gland by immunostaining with antibodies to the a and B subunit isoforms of the enzyme. Immunolabeling of the a l , B1 and B2 isoforms was observed in the apical and lateral plasma membrane domains of prostatic epithelial cells in contrast to human kidney where the al and B1 isoforms of Na+, K+- ATPase were localized in the basolateral membrane of both proximal and dista1 convoluted tubules. Using immunohistochemistry and PCR we found no evidence of Na+, K+-ATPase a 2 and a 3 isoform expression suggesting that prostatic Na+, K+-ATPase consists of allí31 and allí32 isozymes. Our immunohistochemical findings are consistent with previously proposed models placing prostatic Na+, K+-ATPase in the apical plasma membrane domain. Abundant expression of Na+, K+- ATPase in epithelial cells lining tubulo-alveoli in the human prostate gland confirms previous conclusions drawn from biochemical, pharmacological and physiological data and provides further evidence for the critica1 role of this enzyme in prostatic cell physiology and ion homeostasis. Na+, K+-ATPase most likely maintains an inwardly directed Na+ gradient essential for nutrient uptake and active citrate secretion by prostatic epithelial cells. Na+, K+-ATPase may also regulate lumenal Na+ and K+, major counter-ions for citrate
Open Access
Ageing of the human oviduct: lectin histochemistry
(Murcia : F. Hernández, 2001) Gheri, G.; Noci, I.; Sgambati, E.; Borri, P.; Taddei, G.; Gheri Bryk, S.
The aim of the present research was to investigate the changes of the sugar residues in the oviduct in the course of ageing in postmenopausal women vs normally menstruating women, by means of lectin histochemistry. Twenty asymptomatic postmenopausal women (48- 83 years old) were recruited among patients who underwent a vaginal hysterectomy. Eight normally menstruating women were recruited as controls. Fragments of Fallopian tubes (pars ampullaris) were fixed in 10% formalin and routinely processed. The sections were labelled with HRP-lectins (PNA, SBA, DBA, WGA, Con A, LTA, UEAI). Some sections were pre-treated with neuraminidase prior to staining with HRP-lectins. Among the postmenopausal patients, our histochemical data showed that there was no difference in the localization and distribution of sugar residues of glycoconjugates as detected by various HRP-lectins. Moreover, our results demonstrated that the oviductal epithelium is characterized by apical reactivity in both ciliated and non-ciliated cells. In the course of ageing, the ciliated cells changed their morphology from bathyprismatic to large and rounded shape. ConA lectin reacted intensely with such highly degenerating ciliated cells and could be considered a marker of these cells. The degenerating ciliated cells are also characterized by the absence of sialic acid. In comparison with the sugar residues present in the control group, the oviductal epithelium of postmenopausal women is characterized by the loss of reactivity with DBA, WGA and ConA. Moreover, PNA reactive material was present at the free border of the ciliated and non-ciliated cells. The latter findings were statistically confirmed and could be considered strictly related to the ageing process.
Open Access
Significance of proneural basic helix-loop-helix transcription factors in neuroendocrine differentiation of fetal lung epithelial cells and lung carcinoma cells
(Murcia : F. Hernández, 2001) Ito, T.; Udaka, N.; Ikeda, M.; Yazawa, T.; Kageyama, R.; Kitamura, H.
In this brief review article, we describe how cell fate determination by which the airway epithelial cells become neuroendocrine or non-neuroendocrine is regulated by a network of basic helix-loop-helix transcription (bHLH) factors in a similar manner to neurona1 differentiation, and how this system could work to determine cell differentiation of human lung carcinomas. Immunohistochemical studies reveal that mammalina achaete-scute complex homologue (Mash)l is expressed in pulmonary neuroendocrine cells (PNEC), while hairy and Enhancer of split (Hes)l is expressed in pulmonary non-neuroendocrine cells (non-PNEC). Studies using gene-deficient mice for the bHLH factors revealed that in Mashl homozygous null mice no PNEC are detected, while PNEC increase markedly in Hesl homozygous null mice. These obse~at ionss uggest that Mashl is an essential positive factor for neuroendocrine differentiation of lung epithelium, and that Hesl is one of the repressive factors for neuroendocrine differentiation. Moreover, immunohistochemical studies revealed that Notch receptors are detected in non-PNEC, and thus the Notch signalling pathway could play a role in the determination of airway epithelial cell differentiation. In human lung carcinomas, a similar bHLH network should operate to determine cell differentiation phenotypes. Generally, expression of the human homologue of Mashl (HASH1) is detected in small cell carcinoma and carcinoids, while Hesl seems to be expressed mainly in non-small cell carcinoma. Thus, proneuronal bHLH factors may play roles in cell fate determination of the airway epithelial system, and may regulate human airway epithelial cells in diseased conditions.
Open Access
Counts and areas of S-100-positive epidermal dendritic cells in atypical molluscum contagiosum affecting HIV+ patients
(Murcia : F. Hernández, 2001) vera-Sempere, F.J.; Rubio, L.; Massmanian, A.
Molluscum contagiosum is a common and self-limiting viral infection, that in HIV+ patients courses as an opportunist affection with atypical clinical features. Impaired cell-mediated immune response could be involved in such atypical growth. We evaluated the density and area of Langerhans cells (LC) using S-100 immunohistochemistry in seven atypical molluscum contagiosum. LC density was quantified by three different methods using computer-assisted morphometry as well as estimating the relative area of LC with respect to epidermal area. Results were compared with two control groups (normal skin specimens and molluscum contagiosum affecting non-AIDS healthy patients). We found a virtual absence of LC in areas of molluscum lesions affecting both HIV+ and non-AIDS patients. Likewise we observed an evident decrease in LC density in perilesional epidermis of atypical molluscum with respect to both control groups. Upon comparing the counts and areas, we observed that this reduction in LC count was statistically significant only when considering LC related to length of basement membrane in atypical molluscum with respect to normal skin specimens. Our finding of a reduced number of LC in the perilesional epidermis of HIV+ patients with atypical molluscum could explain the high frequency and clinical challenge of molluscum contagiosum in immunocompromised people. In spite of these results, further studies of LC kinetics and functions are required to precisely elucidate their role in the course of molluscum contagiosum in HIV+ patients.
Open Access
Apoptotic cell death and cell proliferative activity in the rat fetal central nervous system from dams administered with ethylnitrosourea (ENU)
(Murcia : F. Hernández, 2001) Katayama, K.; Uetsuka, K.; Ishigami, M.; Nakayama, Hiroyuki; Doi, K.
Ethylnitrosourea (ENU), a weii known DNA alkylating agent, induces anomalies in the central nervous system (CNS), craniofacial tissues and male reproductive organs, and the enhancement of apoptosis is found in these tissues immediately after the administration of ENU (Katayama et al., 2000a). In this study, pregnant rats were treated with 6Omgíkg of ENU at day 13 of gestation, and kinetics of apoptotic cells, mitotic cells and bromodeoxyuridine (BrdU)-positive cells in the fetal CNS were examined from 3 to 48 hours after the treatment (HAT). From 3 HAT, a significant increase in the number of apoptotic cells and a significant decrease in the number of mitotic cells were detected in the fetal CNS, and BrdU-positive cells significantly decreased in accordance with the increase in the number of apoptotic cells. The present results strongly suggest that both excess cell death by apoptosis and cell growth arrest indicated by decreased number of mitotic cells and BrdU-positive cells may have a close relation to the later occurrence of microencephaly following ENU-administration, and that ENU affects mainly S-phase cells and causes apoptosis.
Open Access
lnhibited differentiation of Langerhans cells in the rat epidermis upon systemic treatment with cyclosporin A
(Murcia : F. Hernández, 2001) Borghi-Cirri, M.B.; Riccardi-Arbi, R.; Bacci, S.; Mori, M.; Pimpinelli, N.; Romagnoli, P.; Filipponi, F.
The immunosuppressant drug cyclosporin A (CsA) is known to cause reduction in number, DNA synthesis and function of Langerhans cells (LC). Since also the differentiation of LC is known to be hampered in conditions of acquired immunodeficiency not due to drugs, we investigated whether this occurs with CsA. Rats were injected subcutaneously with CsA (5, 10 and 50 mg.kg-l.d-l) for three weeks; the skin was analyzed by Ia immunohistochemistry and by electron microscopy. Epidermal immunolabeled cells were 1553.5 (mean I SEM) per 100 basa1 keratinocytes in untreated controls and 8.7511.3, 4.7551.0 and 1.751.2 upon increasing doses of CsA (pe0.01). By electron microscopy, monocytoid cells with deep invaginations of the plasma membrane and roundish LC poor in Birbeck granules appeared in the epidermis upon treatment. The results suggest that CsA inhibits the differentiation of LC precursors in the epidermis and that this can in part explain the selective increase in the risk of skin vira1 disease and cancer in chronically treated patients.
Open Access
The histogenesis of giant cell tumour of bone: a model of interaction between neoplastic cells and osteoclasts
(Murcia : F. Hernández, 2001) Zheng, M.H.; Robbins, P.; Xu, J.; Huang, Liping; Wood, D.J.; Papadimitriou, J.M.
Giant cell tumour of bone (GCT) is a benign primary neoplasm of a bone characterised by distinctive clinical, radiological and pathological features. Females are slightly more often affected than males, and the majority of patients present between the ages of 20 and 50. GCT is locally aggressive and produces expansive and lytic lesions, most commonly in the epiphyses of long tubular bones. Histologically, it is composed of oval and spindle mononuclear cells, uniformly distributed amongst which are large multinucleated osteoclast-like giant cells. Although the term "Giant Cell Tumour" (and the erroneous historical term 'osteoclastoma') may imply that it is the multinucleated giant cells which are responsible for the proliferative capacity of the tumour, there is evidence that the stromal-like cells, the major component of the mononuclear celi population, represent the true neoplastic component of the neoplasm. The diagnosis and management of conventional GCT are often challenging and there is considerable current interest in its pathobiology. The precise histogenesis of GCT and the nature of its varying cellular constituents have remained a matter of some controversy. Factors influencing the clinical course and biological aggression of GCT are also unclear. In this selective review, the clinicopathological characteristics of GCT are summarised and current areas of interest in the study of the neoplasm are presented and discussed. Lastly, a hypothetical model of the mechanism of histogenesis and the biological behaviour of GCT is presented.
Open Access
Human lung fructose-1,6-bisphosphatase is localized in pneumocytes II
(Murcia : F. Hernández, 2001) Gizak, A.; Rakus, D.; Kolodziej, J.; Zabel, M.; Ogorzalek, A.; Dzugaj, A.
The localization of fructose-1,6-bisphosphatase (Fru-1,6-Pase EC 3.1.3.11) in human alveolar epithelium was determined immunohistochemically using a polyclonal antibody raised against the enzyme purified from human liver. The immunohistochemical analysis revealed that the Fru-1,6-Pase was localized in pneumocytes 11 and was absent in pneumocytes 1. Hypothetically Fru-1,6-Pase participating in glucose-6-phosphate synthesis from noncarbohydrate precursors increases NADPH leve1 which is used for surfactant synthesis and for glutathione redox cycle.
Open Access
Function of inflammatory cells and neoral cyclosporin-A in heart transplant-associated coronary vasculopathy
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Buján, J.; Jurado, F.; Gimeno, M. J.; Rodriguez, M.; Bellón, J. M.
The role of Sandimmun Neoral® (S-n) and the immune response in transplant-associated coronary vasculopathy (TACV) was evaluated in a Lewis (Lew)- to-Fischer-344 (F344) rat abdominal heterotopic heart transplant model. Some of the transplant recipients were treated with S-n (5mg/ kg/ day) for 14 days posttransplant, or until sacrifice. Grafts were subjected to immunohistochemical (ED1, CD4, CD8 and a-actin+ cells) anal ysis from day 7 to 100 post-transplant. Singenic controls did not develop TACV, irrespective of whether they had received the drug or not. TACV was detected in Lew-F344 transplants regardless of S-n administration with participation of ED1+, CD8+ and aactin+ cells, although its incidence was lower in animals receiving prolonged S-n treatment. In this model, accelerated arteriosclerosis of the graft appeared to be related more to the rejection effect than to the action of the immunosuppressive agent.