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

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Open Access
Prognostic value of p53 protein expression and clinicopathological factors in infiltrating ductal carcinoma of the breast. A study of 192 patients
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Sirvent, J. J.; Fortuño Mar, A.; Olana, M.; Ortí, A.
The p53 gene is located on the short arm of chromosome 17. It encodes a 53-kd nuclear protein (p53) found in scant amounts in normal tissue. Mutations of the p53 gene have been reported in different human tumours. In breast cancer, it has been noted that the overexpression of p53 protein in the nucleus is an indicator of poor prognosis, although there is a high degree of variability, which may be due to different immunohistochemical techniques, varying assessment of results a nd the type of monoclonal antibody used. This study is an immunohistochemical analysis of p53 expression in 192 cases of infiltrating ductal carcinoma of the breast, correlating it with clinicopathological factors and the clinical course of the disease. Of all the breast-cancer tissue analysed, stains for p53 antibody were found in 87 tumours (45.3%). The results of multivariate ana lysis show that the independent predictors related to recurrence are tumour size, Iymphnode metastasis and p53, while those related to death are necrosis, lymph-node metastasis and p53. In summary, our series showed prognostic significance between the expression of p53 and shorter survival time and disease-free interval for all patients in general as well as those who prese nted lymph-node metastases at the time of diagnosis.
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
Morphological study of erythrocyte shapes in red pulp of mouse spleens revealed by an in vivo cryotechnique
(Murcia : F. Hernández, 2001) Xue, M.; Baba, T.; Terada, N.; Kato, Y.; Fuji, Y.; Ohno, S.
The purpose of this study was to clarify erythrocyte shapes in splenic cords of living mouse spleens, using our in vivo cryotechnique followed by scanning (SEM) or transmission (TEM) electron microscopy. Some spleens of mice were quickly frozen by the in vivo cryotechnique while their hearts were beating under anesthesia. In contrast, other spleens were prepared by an in vitro freezing method after they were taken out from the abdominal cavity. They were routinely freeze-substituted, and prepared for SEM and TEM. A few mouse spleens were also routinely fixed and embedded in Quetol-812 to obtain conventional morphology. Erythrocytes in living mouse spleens showed a variety of shapes with narrow spaces between them, trapped among reticular fiber tissues. Similar various shapes of erythrocytes were kept in the red pulp even after blocking normal blood circulation, as prepared by the in vitro freezing method. In comparison to the above-mentioned findings, some erythrocytes were changed to biconcave discoid shapes by the conventional immersion fixation with chemical fixatives. They also showed wide spaces between each other among reticular fiber tissues. Such conventional morphological studies could hardly reveal the in vivo shapes of erythrocytes in functioning spleens with normal blood circulation. In contrast, the various shapes of erythrocytes in the functioning spleens were demonstrated by our in vivo cryotechnique. It is suggested that most erythrocytes congesting in spleens keep their original configuration in spite of microenviromental alteration in splenic blood circulation.
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
A salvianolic acid 8-rich fraction of Sa/via miltiorrhiza induces neointimal cell apoptosis in rabbit angioplasty model
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Hung, H.-H.; Chen, Y.-L.; Lin, S.-J.; Yang, S.-P.; Shih, C.-C.; Shiao, M.-S.; Chang, C.-H.
Apoptosis has been suggested to participate in stabilizing cell number in restenosis. Salvia miltiorrhiza (SM) Bunge which is a Chinese herb widely used for the treatment of cardiovascular disorders contains a potent antioxidant, Salvianolic ac id B. To determ ine whether the antioxidant affects vascular apoptosis, the present study examined the frequency of apoptotic cell death in atherosclerotic plaques and in restenotic lesions of cholesterol-fed rabbits. New Zealand White rabbits were treated with a normal diet (normal), a 2% cholesterol diet (HC), a 2% cholesterol diet and endothe lial denudation (HC-ED), a 2 % cholesterol diet with 5% water-soluble extract of SM (4.8 glKg B. W./day) and endothelial denudation (HCED-SM), or with a 2% cholesterol diet containing probucol (0.6 glkg B.W./day) and endothelial denudation (HC-ED-probucol). Apoptosis and associated cell types were examined in serial paraffin sections by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and immunohistochemistry. The expression of p53, an apoptosis-related protein, was also examined. Apoptosis was mainly detected in the neointima of the three gro ups with endothe lial denudation. The percentage of apoptotic cells in SMtreated group (68.5±5.9%) was significantly higher than that of normal (0 %), HC (1.9±1.2 %), HC-ED (46.1±5.4%), and probucol-treated (32.8±3.9%) groups. The SM treatment markedly reduced the thickness of the neointima which was mainly composed of smooth muscle cells with few macrophages. In accordance with the apoptotic cell counts, positive immunoreactivity for p53 was observed in restenotic lesions from HC-ED, SM-treated and probucol-treated groups but not in the intima of the other two groups. These results suggest that the treatment with salvianolic acid B-rich fraction of SM induces apoptosis in neointima which in turn may help prevent the neointimal thickening.
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
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
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
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
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
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
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
Photodynamic therapy: shedding light on the biochemical pathways regulating porphyrin-mediated cell death
(Murcia : F. Hernández, 2001) Granville, D.J.; McManus, B.M.; Hunt, D.W.C.
Photodynarnic therapy (PDT) is a clinically approved treatment for the ocular condition age-related macular degeneration, and certain types of cancer. PDT is also under investigation for other ocular, as well as, immune-mediated and cardiovascular indications. PDT is a two step procedure. In the first step, the photosensitizer, usually a porphyrin derivative, is administered and taken up by cells. The second step involves activation of the photosensitizer with a specific wavelength of visible light. Exposure to light of an activating wavelength generates reactive oxygen species within cells containing photosensitizer. PDT with porphyrin photosensitizers induces rapid apoptotic cell death, an event which may be attributed to the close association of these compounds with mitochondria. Thus, PDT is an attractive method to treat ailments such as cancer, vira1 infections, autoimmune disorders and certain cardiovascular diseases in which the apoptotic program may be compromised. The present review examines the cellular events triggered at lethal and sublethal PDT doses and their relationship to the subsequent effects exerted upon cells.
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
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
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
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
Histopathological changes in avian kidney caused by Bothrops insularis (jararaca ilhoa) venom and a phospholipase A2-containing fraction
(Murcia : F. Hernández, 2001) da Cruz Hoflingl, M.A.; Paronetto, C.C.L.; Cogo, J.C.; Rodrigues-Simioni, L.; D'Abreu, A.C.F.
The histopathological changes induced in avian kidney by the intramuscular injection of Bothrops insularis (jararaca ilhda) venom and its phospholipase A2 (PLA2)-containing fraction were examined. Acute experiments (3 h and 24 h) with B. insularis crude venom (20 pg and 80 pg) or its PLA2-contaning fraction (10 pg and 40 pg) resulted in significant structural damage to the kidneys of 5-12-day-old chicks. Histopathological analysis indicated that the venom and its fraction acted on the renal tubules and glomeruli. The morphological changes, although widespread, varied in intensity from cell to cell, and from tubule to tubule in venom-injected chicks. The tubular and glomerular changes produced by the venom and its PLA2-containing fraction may be the result of a direct cytotoxic effect potentiated by ischemia-related disturbances in the regional hemodynamics. The venom and its fraction affected more segments along reptilian-type nephrons than along mammalian ones. This divergent sensitivity to the venom and its fraction may reflect the speciesspecific characteristics of B. insularis snake, an example of geographical isolation influencing its diet which is almost exclusively avian.