Histology and histopathology Vol.19, nº 3 (2004)

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Open Access
Effect of telmisartan on preexistent cardiac and renal lesions in spontaneously hypertensive mature rats
(Murcia : F. Hernández, 2004) Mandarim-de-Lacerda, Carlos A.; Pereira, L.M.M.
Fifteen adult male spontaneously hypertensive rats (one year old) (SHR) were separated into three groups (n=5 each) during 15 weeks as follows: initial control group (IC); final control group (FC); and telmisartan group (T) (1.2 mg/kg/day of telmisartan). Serum and urinary creatinine and proteinuria were not different comparing untreated and telmisartan-treated SHRs. FC rats showed a continuous BP increase during the study while T rats reached the 15th week with a significantly low BP. The LV mass index was significantly smaller in the T group than in the FC group, as was the glomerular hypertrophy. The cardiomyocyte nuclei density per area and the cardiomyocyte mean cross-sectional area were smaller in the T group than in both the IC and FC groups. Intramyocardial artery densities (per area and per volume) were greater in the T group than in untreated SHRs, but myocardial fibrosis was reduced. In conclusion, telmisartan monotherapy effects on BP and also on the hypertension target organs, heart and kidney, are favorable. Telmisartan is able to attenuate SHR cardiomyocyte and glomerular hypertrophies, and myocardial reactive fibrosis as well. It also is favorable to the intramyocardial microcirculation.
Open Access
Aberrant expression of a fetal glycoprotein 68 in hepatocellular carcinoma: a comparative study on the expression of alpha-fetoprotein and carcinoembryonic antigen
(Murcia : F. Hernández, 2004) Kato, Massuo J.; Shinozawa, T.; Kato, S.; Terada, T.
A rat IgG2a monoclonal antibody against a stage-specific fetal glycoprotein with a molecular mass of 68 kDa (FGP68) was produced and applied to paraffin sections. This monoclonal antibody was used to compare the expression of FGP68 with that of both alphafetoprotein (AFP) and carcinoembryonic antigen (CEA) in 75 hepatocellular carcinomas (HCCs). Seventy-five primary HCCs from patients aged 36 to 77 years were examined. Formalin-fixed, paraffin-embedded tissue sections were used for immunohistochemical analyses. Histologically, 6 cases of HCC were classified as type I according to the Edmondson and Steiner criteria, 57 cases as type II, and 12 cases as type III. The cancer tissues showed positive reactions with the antibody against FGP68. Approximately one-third of the HCCs (26/75) contained tumor cells that expressed FGP68 - (21/57 for Edmondson and Steiner type II; 4/12 for type III; and 1/6 for type I) - and positive immunoreactivity was observed in the cytoplasm of the cancer cells. Twenty-five of the 75 HCCs had tumor cells that expressed AFP and there was a significant correlation between FGP68 expression and AFP expression. Twenty-three of the 75 HCCs had tumor cells that expressed CEA and there was no significant correlation between FGP68 expression and CEA expression. No positive reactions for FGP68, AFP and CEA were observed in samples of non-neoplastic liver tissues. Based on the possibility that stage-specific FGP68 plays an important role in liver embryogenesis, FGP68- expressing tumor cells might ontogenetically revert to more primitive cells.
Open Access
Transgenic mice overexpressing both amyloid ß-protein and perlecan in pancreatic acinar cells
(Murcia : F. Hernández, 2004) Fukuchi, K.; Hart, M.; Yan, Z.; Hassell, J.R.; Li, L.
Heparan sulfate proteoglycans such as perlecan are thought to facilitate amyloid fibril formation. Tg3695 mice overexpress perlecan core protein in many tissues including the brain and pancreas. Tg13592 mice overexpress the signal plus 99-amino acid carboxyl terminal sequences (C99) of amyloid ß-protein precursor in multiple tissues and develop amyloid deposits in the pancreas. To investigate a role of perlecan in ß-amyloidosis, we established doubly transgenic mice by crossing the two lines of transgenic mice. The expression levels of the two transgenes remained unchanged in the brain and pancreas and the doubly transgenic mice did not develop amyloid deposits in the brain up to 19-months of age. Amyloid load detected by thioflavine S in the pancreas of the doubly transgenic mice was not significantly different from that in the transgenic littermates expressing only C99. Amyloid load in the pancreas increased during aging. We found a positive correlation between the Aß-immunoreactive (non-fibrillar and fibrillar) and thioflavine S-positive (fibrillar) Aß deposits in the single (C99) but not doubly transgenic mice. Our results suggest that perlecan does not independently influence amyloid formation in the pancreas of the transgenic mice and that there may be other factors that may modulate amyloid formation together with perlecan.
Open Access
Lectin cytochemistry on developing rat submandibular gland primary cultures
(Murcia : F. Hernández, 2004) Sabbieti, M.G.; Gabrielli, M.G.; Menghi, Giovanna; Materazzi, G.; Marchetti, L.
Lectin cytochemistry was performed in vitro on primary cultures from the rat submandibular gland. For this purpose, prepubertal rats (17, 27, 33 days old) of both sexes were used. Several types of medium supplements were tested and it was found that cells survived until 15 days in presence of all medium supplements and extracellular matrix gel. The binding patterns of all FITC/TRITC-labeled lectins, with and without prior sialidase digestion and deacetylation, were analyzed in a confocal laser scanning microscope. In particular, the occurrence of C4 acetylated sialic acid linked to ß-galactose at day 27 and the presence of fucose residues at day 33 indicated that lectin probes applied to cultured cells give results similar to those obtained in intact tissues and can be used as markers of growth and differentiation.
Open Access
Corticosterone 21-acetate in vivo induces acute stress in chicken thymus: cell proliferation, apoptosis and cytokine responses
(Murcia : F. Hernández, 2004) Franchini, A.; Marchesini, E.; Ottaviani, E.
In vivo effects of acute stress induced by corticosterone 21-acetate in male Gallus domesticus thymus are studied and the steroid actions are evaluated in terms of cell proliferation, apoptosis and cytokine response in 10- and 21-day-old chickens. Steroid treatment induced thymocyte apoptosis and cell death decreased in the cortical-medullar direction and was more evident in younger animals. 24 h after treatment, the observed effect was reversed. The mitotic activity and thymic cells containing cytokine-like molecules were also affected. Indeed, the acute stress stimulated cytokine immunoreactivity to anti-IL-1a, IL-6 and TNF- a antibodies both in epithelial cells and interdigitating cells located in medullar and cortical-medullar regions. The increased cytokine expression observed after 12 h was maintained after 24 h. The comparison between 10- and 21-day-old chickens showed a lower number of cells containing cytokine-like molecules in younger specimens. The present findings suggest that cytokines activated by acute stress in vivo could contribute to restoring immunological homeostasis and influence thymic glucocorticoid-mediated functions.
Open Access
Age-related changes of the ultrastructure in the cardiomyopathic hamster (UM-X7.1 Syrian hamster) parathyroid gland
(Murcia : F. Hernández, 2004) Utsumi, M.; Moriguchi, K.; Takahashi, H.; Kinoshita, C.; Togari, A.; Mizutani, M.; Ohno, N.
We qualitatively and quantitatively investigated parathyroid glands of the UM-X7.1 cardiomyopathic hamster at 1, 2, 6 and 12 months of age to compare them with those of the normal hamster. We found that at 1 month of age in the UM-X7.1 hamster, the Golgi apparatus, lipid droplets and secretory granules decreased. There were no significant differences between the UM-X7.1 hamster and the control hamster at 2 months of age. At 6 months of age, the Golgi apparatus, rER and the secretory granules significantly increased in the UM-X7.1 hamster. At 12 months of age, the Golgi apparatus and lysosomes increased, while the secretory granules decreased. Ultrastructurally, we consider that in the UM-X7.1 hamster, the synthesis and release of the parathyroid at 6 months of age may be activated by an excessive amount of circulating catecholamine, and the functional activity of the parathyroid glands at 12 months of age may be depressed by the increased plasma calcium level. These findings suggest that the activities of the synthesis and release of the parathyroid hormone were the highest at 6 months of age in the UM-X7.1 hamster.
Open Access
Multiparameter analysis of AgNOR in thyroid lesions: comparison with PCNA expression
(Murcia : F. Hernández, 2004) Slowinska-Klencka, D.; Klencki, M.; Popowicz, B.; Sporny, S.; Lewinski, A.
The aim of the study was to examine numerous features of argyrophilic proteins related to nucleolar organizer regions (AgNORs) in thyroid tumors, relate them to PCNA expression and evaluate which of these features might be useful in the diagnosis of thyroid lesions. Paraffin sections of 100 thyroid tumors were silver-stained and divided into 9 groups: nodular goiter (NG), simple adenoma (SA), microfollicular adenoma (MFA), follicular carcinoma (FC), follicular variant of papillary carcinoma (PC-F), classical variant of papillary carcinoma (PC-C), Hürthle cell adenoma (HA), Hürthle cell carcinoma (HC), and anaplastic carcinoma (AC). The slides were analyzed with the computerized system for image analysis. A weak correlation was found between PCNA expression and AgNOR size. AC differed significantly from all other examined groups in many features of AgNOR dots. Hürthle cell neoplasms were characterized by the presence of a usually single and relatively large dot. With respect to diagnosing follicular lesions, we found that the evaluation of the total area of dots in the nucleus seemed to be the most useful for discrimination: the assumption of 4.9 µm2, as a cut-off value, allowed a correct classification of 77% of FC cases. Computeraided morphometric analysis of AgNORs may be useful in the diagnostics of thyroid lesions.
Open Access
Comparative analysis of cell populations involved in the proliferative and inflammatory processes in diffuse and localised pigmented villonodular synovitis
(Murcia : F. Hernández, 2004) Berger, I.; Ehemann, V.; Helmchen, B.; Penzel, R.; Weckauf, H.
The aim of the present study was a comparative quantitative evaluation of cell populations involved in the proliferative and inflammatory compartment in both localised and diffuse pigmented synovitis villonodularis (PVNS). 15 cases of each localised and diffuse PVNS were examined by flow cytometry, immunohistochemistry, double immunofluorescence and confocal microscopy with quantitative evaluation of CD3-, CD4-, CD8-, CD20-, CD57-, CD55-, CD68-, CD163- and h4Ph positive (+) cells. The proliferative compartment of localised and diffuse PVNS was mainly composed of double-positive CD68+/h4Ph+ (CD163+/CD55+) synoviocytes. The number of doublepositive synoviocytes for macrophage and fibroblast markers was significantly higher in diffuse compared to localised PVNS. The accompanying inflammatory infiltrate showed a predominance of cytotoxic cells (CD8+, CD57+), whereby the number of CD3+ and CD20+ cells was significantly higher in localised PVNS. The number of CD57+ NK cells was significantly higher in diffuse PVNS. The proliferating macrophage- like synovial cells and the cytotoxic lymphocytes could contribute to the aggressive behaviour of localised and diffuse PVNS. Moreover, with regard to the quantitative differences in cell composition between diffuse and localised PVNS and their different clinical behaviour, further studies should continue to analyse localised and diffuse PVNS separately.
Open Access
Neuropeptides, apoptosis and ion changes in prostate cancer. Methods of study and recent developments
(Murcia : F. Hernández, 2004) Vilches, J.; Salido, M.; Fernández-Segura, E.; Roomans, G.M.
It has been suggested that neuroendocrine (NE) cells provide paracrine stimuli for the propagation of local carcinoma cells and that NE differentiation is associated with the progression of prostate cancer toward an androgen-independent state. Apoptosis comprises a critical intracellular defense mechanism against tumorigenic growth and is associated with a number of changes in the elemental content of the cell. The neuropeptides bombesin and calcitonin, which inhibit etoposide-induced apoptosis, also inhibit the etoposide-induced elemental changes in prostate carcinoma cells. This important fact strengthens the link between apoptosis and changes in the intracellular elemental content. This protective effect on etoposideinduced apoptosis appears to be quite similar in androgen-dependent and androgen-independent cell lines. This confirms that neuropeptides confer antiapoptotic capabilities on non-neuroendocrine cells in close proximity to neuroendocrine cells. It can therefore be speculated that certain neuroendocrine peptides can increase the survival and further growth of neighboring cells and may thereby contribute to the aggressive clinical course of prostate tumors containing neuroendocrine elements. In addition, this correlation provides an objective basis for the study of neuropeptide target points and may be helpful for alternative therapeutic protocols using neuropeptide inhibitors in the treatment of patients with advanced prostatic carcinoma. The culture techniques described were, thus, designed in order to achieve two important goals. First, the development of an in vitro model that allows an approach to neuroendocrine differentiation in prostate cancer and its role in apoptosis blockage. Second, the method has been designed in order to permit rapid cryofixation of intact cell monolayers for subsequent xray microanalysis.
Open Access
Dietary aluminium and renal failure in the Koala (Phascolarctos cinereus)
(Murcia : F. Hernández, 2004) Haynes, J.I.; Askew, M.J.; Leigh, C.
The study investigated the link between the potentially nephrotoxic levels of aluminium ingested in the natural diet of eucalypt leaves by koalas in the Adelaide Hills, South Australia, and the high incidence of renal failure in koalas within this habitat. Routine histology of kidney specimens revealed no pathologies at the light microscopic level and contrasted sharply with the clinical signs of renal failure. However staining with solochrome azurine and Perl’s Prussian blue showed aluminium was present in some proximal convoluted tubules in all specimens. Aluminium was also found in bone samples. The presence of aluminium in bone and kidney tissues was confirmed using electron dispersive x-ray analysis with transmission and scanning electron microscopy. Ultrastructural changes, including a decrease in lysosomal numbers, were seen in proximal convoluted tubules and these changes were shown to coincide with the presence of aluminium. No aluminium was found in koalas that died from causes other than renal failure. It was concluded that renal failure in the koalas of the Adelaide Hills is characterised by the presence of aluminium in the kidneys and bone and it is probably related to the high levels of aluminium in their restricted diet of eucalypt leaves. However, it is not known if the presence of aluminium is the cause or effect of the renal failure. The study is the first account where aluminium ingested as part of the natural diet of mammals has been shown to accumulate in the animal and be implicated with nephrotoxicity.
Open Access
On the role of the islets of Langerhans in pancreatic cancer
(Murcia : F. Hernández, 2004) Hennig, R.; Ding, X.Z.; Adrian, T.E.
Pancreatic cancer is a devastating disease characterized by a dismal prognosis with most patients dying within six months after diagnosis. Surgery is an option in less than one in five of these patients, and even with tumor resection the majority of patients succumb to the disease. Other effective treatment options are not available. Common features of pancreatic cancer are severe cachexia, marked insulin resistance and diabetes mellitus. Several studies have demonstrated connections between pancreatic cancers and the endocrine pancreas and this has raised questions regarding the role of the islets of Langerhans in pancreatic adenocarcinoma. This manuscript reviews the recent literature in this field and addresses several questions regarding the interaction between the islets of Langerhans and pancreatic cancer. This review considers the histological findings in pancreatic cancer, cell culture and animal experiments, the four islet cell types and the hormones they secrete, as well as the influence of the arachidonic acid pathways on islet cell function and pancreatic cancer. While pancreatic adenocarcinomas are ductal in nature, the cell of origin has not been identified and there is even some evidence that the islets may harbor the precursor cell. Considerable evidence suggests that the diabetes is caused by the tumor, while other studies have identified diabetes as a risk factor. Clearly, the islets are important in many aspects of this disease. However, even though progress has been made, some questions regarding the interaction of pancreatic cancer and the endocrine pancreas remain unanswered.
Open Access
Intra- and extracellular Aß and PHF in clinically evaluated cases of Alzheimer’s disease
(Murcia : F. Hernández, 2004) Fernández-Vizarra, P.; Fernández, A.P.; Castro-Blanco, S.; Serrano, J.; Bentura, M.L.; Martínez Murillo, R.; Martínez, A.; Rodrigo, J.
Temporal cortical sections from postmortem brains of individuals without any dementing condition and with different degrees of severity of Alzheimer’s disease (AD) evaluated by the Clinical Dementia Rating scale (CDR 0-CDR 3) were analyzed using immunohistochemical procedures. To demonstrate the amyloid-ß-peptide (Aß) deposition and the neurofibrillary pathology, two monoclonal antibodies were used, a human CERAD Aß (10D5) antibody raised against the N-terminal region of the Aß-peptide, and an antibody raised against paired helical filaments (PHF-1). The neuron cell bodies and the glial cells were also recognized by two polyclonal antibodies raised, respectively, against the protein gene peptide (PGP 9.5) and glial fibrillary acidic protein (GFAP). Directly related to severity of AD, progressive deposits of Aßpeptide were found within cortical pyramidal-like neurons and forming senile plaques. Ultrastructurally, Aß-peptide deposits were related to neuronal intracytoplasmic organelles, such as the ER, the mitochondria, the Nissl bodies and lipofuscin. We have also found that the intracellular deposition of the Aß peptide is a neuropathological finding prior to the appearance of PHF-immunoreactive structures. We suggest that the intracellular Aß deposition in cortical pyramidal neurons is a first neurodegenerative event in AD development and that it is involved in cell dysfunction, neuronal death, and plaque formation
Open Access
Angiogenesis and the role of bone marrow endothelial cells in haematological malignancies
(Murcia : F. Hernández, 2004) De Raeve, H.; Van Marck, E.; Van Camp, B.; Vanderkerken, K.
Increased microvessel density (MVD) has been observed in the bone marrow (BM) of patients with multiple myeloma (MM), acute lymphoblastic leukaemia, acute myeloid leukaemia, and myelodysplastic and myeloproliferative syndrome. The MVD is the net result of cumulative phases of angiogenesis and angio-regression and is as such not an indicator of the ongoing angiogenesis at the time of biopsy. There is, therefore, a need for additional methods that allow the estimation of ongoing angiogenesis. Double immunostainings for CD34 and Ki-67 can be used on paraffin-embedded tissue to determine the endothelial proliferation fraction. The BM endothelial cells, as a component of the BM stroma, have a close interaction with the malignant cells. In MM, for example, they are involved in the specific homing and are a source of paracrine growth factors. Targeting the BM microvessels will not only influence the nutrient and oxygen supply, but will in addition reduce the growth stimuli provided by the EC.
Open Access
Pulmonary lymphoid lesions in an experimental model of collapsing glomerulopathy in rats
(Murcia : F. Hernández, 2004) Ávila-Casado, M.C.; Pérez-Torres, I.; Aurón, A.; Zepeda Rodríguez, A.; Soto, V.; Soria, E.; Hernández, S.; Chávez-Rentería, B.; Mussali-Galante, Patricia; Ávila-Costa, M.R.; Fortoul, T.I.
The characterization of lung damage in an experimental model of collapsing glomerulopathy (CG) in rats is described. Methods: 12 rats were divided into two groups and injected intravenously (iv) with 1 mg/ saline in a final volume of 1 ml/ day in the tail vein for 5 days, with fractionated serum from control and CG subjects. Proteinuria was quantified, and the Glomerular filtration rate was calculated based on creatinine clearance (CC). Rats were sacrificed by perfusion fixation at day 5. Results: Rats injected with serum from CG patients developed proteinuria (p<0.001). A decrease in CC (0.68±0.19) in these rats was also observed. Glomerular tuft retraction and mesangial proliferation was observed in all rats receiving serum from the CG patients. Peribronchiolar infiltrate integrated mainly by lymphocytes, was identified in all CG rats. In some areas this infiltration disrupted the basement membrane and damaged the epithelium. No histopathological abnormalities in the kidney or lungs were found in rats receiving control serum. Conclusion: Patchy pulmonary lymphoid infiltrates were found in the CG model. Up to now there was no information about pulmonary lymphoid infiltration in CG patients. Besides fluid overload due to renal insufficiency or a nephrotic syndrome, other causes of pulmonary involvement in CG patients should be explored.
Open Access
Immune signals in the context of secondary osteoporosis
(Murcia : F. Hernández, 2004) Okada, Y.; Tanaka, Y.
Bone homeostasis is maintained by a balance between bone resorption by osteoclasts and bone formation by osteoblasts, and alterations in bone metabolism can lead to diseases such as osteoporosis. Inter-cellular and intra-cellular signaling, originating from the immune system, the largest source of cellderived regulatory signals, are involved in these processes. Immune-competent cells such as macrophages and lymphocytes deliver cell-cell signaling through soluble factors such as cytokines and through direct contact with the cells. Such immunological signals to the bone are transmitted primarily through osteoblasts or direct stimulation of osteoclasts to induce osteoclast maturation or bone resorption, which may in turn lead to the disequilibrium of bone metabolism. Inflammatory diseases such as rheumatoid arthritis are good examples of such a process, in which immunological signals play a central role in the pathogenesis of the accompanying secondary osteoporosis. We will achieve a better understanding of the pathogenesis of bone metabolism in osteoporosis through immune signaling, and thereby develop improved therapeutic strategies for these conditions.
Open Access
Distribution and role of CD34-positive stromal cells and myofibroblasts in human normal testicular stroma
(Murcia : F. Hernández, 2004) Kuroda, Naoto; Nakayama, Hiroyuki; Miyazaki, E.; Hayashi, Yoshihiro; Toi, M.; Hiroi, Makoto; Enzan, H.
CD34-positive stromal cells are distributed in various organs including breast, Fallopian tubes, thyroid gland, colon, pancreas, and uterine cervix. To elucidate the distribution of CD34-positive stromal cells, smooth muscle cells, and myofibroblasts in normal human testis, we examined 48 testes obtained by autopsy and operation, including five fetal, one neonatal, and 42 adult cases without evident testicular lesions, using a streptavidin-biotin immunoperoxidase technique. The expression of alpha-smooth muscle actin (ASMA), hcaldesmon, CD34, and CD31 were immunohistochemically examined in all cases. The tunica albuginea and the inner layer of seminiferous tubules in adult testis were predominantly composed of myofibroblasts. Smooth muscle cells were also scattered throughout these sites in some cases. CD34-positive stromal cells were abundant, and they formed a reticular network around the seminiferous tubules and Leydig cells as well as the outer layer of seminiferous tubules. Moreover, myofibroblasts and the CD34 reticular network were already present in the testicular stroma during fetal or neonatal development. Double immunostaining of fetal, neonatal and adult testes using ASMA and CD34 confirmed that myofibroblasts and CD34-positive stromal cells were present in the inner and outer layers of peritubular tissue, respectively. This distribution and cytological identification was also confirmed by an ultrastructural study of four cases. Finally, CD34- positive stromal cells and myofibroblasts are major components of human testicular stroma.
Open Access
Ultrastructural changes in bones of the senescence-accelerated mouse (SAMP6): a murine model for senile osteoporosis
(Murcia : F. Hernández, 2004) chen, H.; Shoumura, S.; Emura, S.
SAMP6, a substrain of senescenceaccelerated mice, was developed as an animal model for senile osteoporosis. In the present study, we investigated the bone morphology, together with serum calcium and bone mineral density (BMD) in SAMP6 and agematched normal mice SAMR1. We did not find any significant differences between SAMR1 and SAMP6 at 1 month of age with regard to the serum compositions and bone morphology. As compared with SAMR1, BMD, the femoral weight, femoral calcium and phosphorus levels were significantly reduced in SAMP6 at 2 and 5 months of age. The number of osteoblasts in trabecular bones was also significantly reduced. Swollen mitochondria and myelin-like structures were found in osteoblasts and osteocytes of SAMP6 mice at 2 and 5 months of age. There was a greater proportion of resting surface and less forming surface in the femoral endosteal surfaces of SAMP6 mice. The amount of trabecular bone in the lumbar vertebra and the distal metaphysis of the femur was reduced. The number of the mast cells in bone marrow of the tibia significantly increased in SAMP6 mice. These findings indicate that the lower bone mass in SAMP6 was due to the reduction in osteoblast formation and suggested that mast cells in bone marrows play a role in the pathogenesis of senile osteoporosis.
Open Access
Animal models of pheochromocytoma
(Murcia : F. Hernández, 2004) Tischler, A.S.; Powers, J.F.; Alroy, J.
Pheochromocytomas are neuroendocrine tumors of adrenal chromaffin cells. They are rare in all species except rats but occur with increased frequency in several human familial tumor syndromes. Concurrence of pheochromocytoma with other tumors sometimes parallels these human syndromes in rats, bovines, horses and dogs but a shared genetic basis for human and spontaneously occurring animal pheochromocytomas has thus far not been established. Pheochromocytomas are inducible in rats by a variety of non-genotoxic substances that may act indirectly by stimulating chromaffin cell proliferation. They are not known to be similarly inducible in other species but arise with increased frequency in transgenic and knockout mice that to varying degrees recapitulate human tumor syndromes. Preliminary evidence suggests that homologous somatic genetic changes might contribute to pheochromocytoma development in humans and some mouse models. The nerve growth factor-responsive PC12 cell line, established from a rat pheochromocytoma, has for almost 30 years served as a research tool for many aspects of neurobiology involving normal and neoplastic conditions. Recently developed pheochromocytoma cell lines from neurofibromatosis knockout mice supplement the PC12 line and have generated additional applications. Advantages of the mouse lines include expression of substantial levels of the epinephrine-synthesizing enzyme, phenylethanolamine N-methyltransferase and expression of high levels of the receptor tyrosine kinase, Ret, which is characteristic of sporadic and familial human pheochromocytomas but not of PC12 cells. Disadvantages include an apparently less stable phenotype. It is difficult to establish pheochromocytoma cell lines from any species, although the tumor cells persist in culture for many months. Understanding of factors that permit pheochromocytoma cells to proliferate might itself provide important insights for tumor biology.
Open Access
The role of apoptosis in pulmonary fibrosis
(Murcia : F. Hernández, 2004) Kuwano, K.; Hagimoto, N.; Nakanishi, Y.
Pulmonary fibrosis is a common response to various injuries to the lung. The resolution of a fibroproliferative response after lung injury is key to survival. Although there are various initiating factors or causes, the terminal stages are characterized by proliferation and progressive accumulation of connective tissue replacing normal functional parenchyma. Conventional therapy consisting of glucocorticoids or immunosuppressive drugs is usually ineffective in preventing progression of fibrosis. Further understanding of the molecular mechanisms of endothelial and epithelial cell injury, inflammatory reaction, fibroblast proliferation, collagen deposition and tissue remodeling, should lead to the development of effective treatments against pulmonary fibrosis. Evidence that apoptosis plays an important role in the pathophysiology of pulmonary fibrosis has been accumulated. We overview the role of apoptosis in each of the pathogenic events which have emerged from animal models and human tissue studies.
Open Access
Expression of MAL and MAL2, two elements of the protein machinery for raft-mediated transport, in normal and neoplastic human tissue
(Murcia : F. Hernández, 2004) Marazuela, M.; Alonso, M. A.
Polarized transport of lipids and proteins to the apical and basolateral membrane subdomains is essential for the functioning of epithelial cells. Apical transport is mediated by a direct route from the Golgi and an indirect route, referred to as transcytosis, involving the transport of the protein to the basolateral membrane followed by its internalization and subsequent transcellular transport to the apical subdomain. MAL and MAL2 have been demonstrated to be essential components of the machinery for the direct and indirect routes, respectively. Herein, we review the range of expression of MAL and MAL2 in normal human tissue and compare it with that of neoplastic tissue. Our analysis provides insight into the potential use of MALand MAL2-mediated pathways in many types of epithelial cells as well as in nonepithelial cells. In addition, the specific alterations in MAL and/or MAL2 expression observed in specific types of carcinoma provides a basis to understand the loss of the polarized phenotype that frequently accompanies the neoplastic transformation process. This points out potential applications of MAL and MAL2 as markers for tumor characterization.