Histology and histopathology Vol.14, nº 2 (1999)

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Open Access
A putative role for calpain in demyelination associated with optic neuritis
(Murcia : F. Hernández, 1999) Banik, N.L.; Shields, D.C.
Calcium activated neutral proteinase (calpain) is an endopeptidase present in the central nervous system which degrades myelin proteins. To examine the role of calpain in demyelination associated with optic neuritis, immunocytochemical expression of calpain was evaluated in Lewis rats with experimental optic neuritis. Calpain expression was increased in activated microglia, infiltrating macrophages, activated T cells, and reactive astrocytes in experimental optic neuritis compared to controls. Calpain activity and translational expression were also examined by Western blotting studies measuring the extent of myelin protein degradation, calpain-specific fodrin proteolysis, axonal neurofilament degradation, and calpain proenzyme content. Results showed myelin associated glycoprotein and 68 kD neurofilament protein levels were significantly decreased while calpain translational expression and calpain-autolyzed fodrin levels were significantly increased in experimental optic neuritis compared to controls. Thus, increased activity and translational expression of calpain in optic neuritis may be integral to the pathogenesis of this disorder.
Open Access
Cytological and functional aspects of telornere maintenance
(Murcia : F. Hernández, 1999) Dandjinou, A.T.; Dionne, I.; Gravel, S.; LeBel, C.; Parenteau, J.; Wellinger, R.J.
The fact that eukaryotic chromosomes are linear poses a special problem for their maintenance: the natural ends of chromosomes must be distinguished from ends generated by chromosomal breakage and somehow, the chromosome ends must also be fully replicated to maintain their integrity. Telomeres, the complex structures at the ends of chromosomes are thought to be instrumental for both of these functions. However, recent insights in telomere biology suggest that these terminal structures do much more than just fulfil1 these two basic functions. Cytological data demonstrate that telomeres may play leading roles in chromatin organization and nuclear architecture during mitosis and meiosis. Moreover, non-functional telomeres may lead to genetic instability, a common prelude to cancer. Here, we review the basic functions of telomeres during chromosome replication and discuss the cytological aspects of telomere function during mitosis and meiosis.
Open Access
Ultrastructural localization of acetylcholinesterase AChE activity in the chicken Harderian gland
(Murcia : F. Hernández, 1999) Hiramatsu, K.; Ohshima, K.
Localization of acetylcholinesterase (AChE) was investigated in the chicken Harderian gland at the electron microscopic level. Nerve cells in the pterygopalatine ganglion showed AChE activity. They had a pale and large nucleus which was round or oval in shape. Reaction product of AChE was detected between the nuclear envelopes, in the cisterna of rough endoplasmic reticulum and the lumen of the Golgi lamellae, and on the plasma membrane of the nerve cell. In the interstitium of the gland, nerve fibers showing AChE activity were easily found. They were often seen in the perivascular space and between plasma cells. These neve fibers had varicosities in contact with plasma cells and the endothelium or the smooth muscle fiber of the blood vessels. AChE-positive varicosities or terminals contained many small clear vesicles (about 50nm in diameter) and a few large dense-cored vesicles (about 100 nm in diameter). No contacts of nerve fibers with acinar cells or the ductal epithelium were observed in the present study. Our data indicate that cholinergic nerves play distinct roles in the regulation of the immune function of the chicken Harderian gland.
Open Access
Hepatotoxicity induced by the anti-oxidant food additive, butylated hydroxytoluene BHT, in rats. An electron microscopical study
(Murcia : F. Hernández, 1999) Safer, A.M.; Al-Nughamish, A.J.
The anti-oxidant food additive, butylated hydroxytoluene (BHT), was fed to Sprague-Dawley rats at three concentrations: 0.2%, 0.4% and 0.8% for periods of 6, 12, 18 and 24 weeks, and the results were compared with corresponging groups treated with a potent carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA) groups, with olive oil, and with untreated control groups. BHT resulted in a significant increase in liver weight. The liver cells presented gradual vacuolization, cytoplasmic disintegration, "moth-eaten" appearance, ballooning degeneration, hepatocellular necrosis, aggregation of chromatin material around the periphery of the nuclear envelope, SER proliferation, RER clumping with broken cisternae, withered and autolyzed mitochondria, augmentation of lipid droplets and glycogen depletion. On the other hand, there was no sign of tumorigenicity. Whether or not BHT acts as a carcinogen in long-term administration may depend not only upon the organ system examined, but also on the strain of the animal used.
Open Access
The molecular pathology of Barrett's esophagus
(Murcia : F. Hernández, 1999) Werner, M.; Mueller, J.; Walch, A.; Hofler, H.
The incidence of adenocarcinoma of the distal esophagus is rapidly increasing in the Western world. The histopathological sequence of (Barrett's) metaplasia, which develops as a consequence of chronic reflux, to dysplasia and then to carcinoma is well established for these tumors. In Barrett's esophagus a variety of molecular changes have been characterized and correlated with tumor initiation and progression. Among the early changes in premalignant stages of metaplasia are alterations of the transcripts of FHIT, a presumptive tumor suppressor gene which spans the common fragile site FRA3B. Mutations of p53 seem to accumulate mainly in the transition from low to high grade dysplasia. Inactivation of other tumor suppressor genes by mutation (APC, p16) or hypermethylation (p16) as well as amplification of oncogenes such as cerbB2 are relatively late events in the development of adenocarcinoma. Among the phenotypic changes in Barrett's esophagus are an expansion of the Ki67 proliferation compartment which correlates with the degree of dysplasia. Moreover, accumulation of rabll molecules which are involved in membrane trafficking has been reported to be specific for the loss of polarity seen in low grade dysplasia. Reduced expression of the cadherinlcatenin complex as well as increased expression of various proteases develop chiefly in invasive carcinomas. Despite the progress that has been made in the identification of molecular markers in Barrett's carcinoma, to date the histopathogical diagnosis of high grade dysplasia in endoscopic biopsies remains the best predictor of invasive cancer. Immunohistochemistry applying a panel of antibodies including p53, Mib-l or rabll can be helpful to diagnose regenerative metaplastic epithelium or low and high grade dysplasia.
Open Access
Antinuclear antibody-keratinocyte interactions in photosensitive cutaneous lupus erythematosus
(Murcia : F. Hernández, 1999) Furukawa, F.
Autoimmune diseases are characterized by various circulating autoantibodies, especially antinuclear antibodies (ANA). It has been a long-standing issue as to whether andlor how ANA interact with epidermal cells to produce skin lesions. Of these ANA, the anti-SS-AIR0 antibody is the most closely associated with photosensitivity in patients with systemic lupus erythematosus (SLE) and its subgroups, including subacute cutaneous lupus erythematosus (SCLE) and neonatal lupus erythematosus (NLE). SS-A/Ro antigens are present in the nucleus and cytoplasm, and interestingly, ultraviolet B (UVB) light translocates these antigens to the surface of the cultured keratinocytes. Thus, anti-SS-AIR0 antibodies in the sera can bind to the relevant antigens expressed on the UVB-irradiated keratinocyte surface, and have been speculated to be an important inducer of antibody-dependent keratinocyte damage. This interaction between the anti-SS-A/Ro antibodies and UVBirradiated keratinocytes may induce the skin lesions through a cytotoxic mechanism. This review will focus on the involvement of antibody-dependent cellular cytotoxicity in the pathogenesis of the skin lesions observed in photosensitive cutaneous lupus erythernatosus.
Open Access
The foveal photoreceptor mosaic in the pipefish, Corythoichthyes paxtoni Syngnathidae, Teleostei
(Murcia : F. Hernández, 1999) Collin, S.P.; Collin, H.B.
The foveal and non-foveal retinal regions of the pipefish, Corythoichthyes paxtoni (Syngnathidae, Teleostei) are examined at the level of the light and electron microscopes. The pipefish possesses a deep, pit (convexiclivate) fovea which, although lacking the displacement of the inner retinal layers as described in other vertebrate foveae, is characterised by the exclusion of rods, a marked increase in the density of photoreceptors and a regular square mosaic of four double cones surrounding a central single cone. In the perifoveal and peripheral retinal regions, the photoreceptor mosaic is disrupted by the insertion of large numbers of rods, which reduce spatial resolving power but may uniformly increase sensitivity for off-axis rays. In addition to a temporal fovea subtending the frontal binocular field, there is also a central area centralis subtending the monocular visual field. Based on morphological comparisons with other foveate teleosts, four foveal types are characterised and foveal function discussed with respect to the theoretical advantage of a regular square mosaic.
Open Access
Human osteoclast ontogeny and pathological bone resorption
(Murcia : F. Hernández, 1999) Athanasou, N.A.; Sabokbar, A.
Monocytes and macrophages are capable of degrading both the mineral and organic components of bone and are known to secrete local factors which stimulate host osteoclastic bone resorption. Recent studies have shown that monocytes and macrophages, including those isolated from neoplastic and inflammatory lesions, can also be induced to differentiate into cells that show all the cytochemical and functional characteristics of mature osteoclasts, including lacunar bone resorption. Monocyte/macrophage- osteoclast differentiation occurs in the presence of osteoblasts/bone stromal cells (which express osteoclast differentiation factor) and macrophage-colony stimulating factor and is inhibited by osteoprotegerin. Various systemic hormones and local factors (eg cytokines, growth factors, prostaglandins) modulate osteoclast formation by controlling these cellular and humoral elements. Various pathological lesions of bone and joint (eg carcinomatous metastases, arthritis, aseptic loosening) are associated with osteolysis. These lesions generally contain a chronic inflammatory infiltrate in which macrophages form a significant fraction. One cellular mechanism whereby pathological bone resorption may be effected is through generation of increased numbers of bone-resorbing osteoclasts from macrophages. Production of humoral factors which stimulate mononuclear phagocyte-osteoclast differentiation and osteoclast activity is also likely to influence the extent of pathological bone resorption.
Open Access
Collagen-platelet interaction, platelet non-integrin receptors
(Murcia : F. Hernández, 1999) Chiang, T.M.
Platelet-collagen interaction is a complex event that involves ligand-receptor interaction. There are many adhesive non-integrin receptors for platelets to interact with various types of collagens. These nonintegrin receptors also serve as signal transducers both from the outside of platelets to the inside and possibly vice versa. The present review covers basic aspects of non-integrin receptor function and various signal transduction pathways.
Open Access
Changes in intestinal endocrine cells in the mouse after unilateral cervical vagotomy
(Murcia : F. Hernández, 1999) Qian, B.F.; El-Salhy, M.; Danielsson, A.; Shalaby, A.; Axelsson, H.
The effect of right or left unilateral cervical vagotomy on the intestinal endocrine cells was studied in 23 mice at 2 and 8 weeks after operation, respectively. The results were compared with that from 10 sham operated mice. Various types of endocrine cells in duodenum and proximal colon were detected by immunohistochemistry and quantified by computerized image analysis. In mouse duodenum, chromogranin-, CCKIgastrin-, GIP- and somatostatin-cells were significantly decreased at 2 weeks after right vagotomy, but returned to the control levels at 8 weeks. Serotonincells were reduced at both 2 and 8 weeks after right vagotomy. The amount of the duodenal endocrine cells did not change after left vagotomy with the exception of secretin-cells, which were diminished at 8 weeks after both right and left vagotomy. In the proximal colon, chromogranin-cells were also decreased at 2 weeks after right vagotomy. Serotonin-cells were reduced at 8 weeks after left vagotomy but not right vagotomy. There was no significant difference between the unilaterally vagotomized and the sham operated mice with regard to PYY- and glucagon-cells. It was concluded that vagotomy affected the intestinal endocrine cells in mouse. The influence was more pronounced in the small intestine than the proximal colon. The right vagus nerves seemed to exert more effect on the intestinal endocrine cells than the left ones.
Open Access
Detection and significance of minimal residual disease in colorectal cancer
(Murcia : F. Hernández, 1999) Merrie, A.E.H.; Yun, K.; van Rij, A.M.; McCall, J.L.
Colorectal cancer (CRC) is one of the most common causes of cancer death in the developed world. Although the primary treatment for CRC is surgical, disease relapse due to minimal residual disease (MRD) following apparently curative surgery occurs in up to fifty percent of patients. Most patients who develop overt metastases beyond the regional lymph nodes eventually die of the disease. At present adjuvant chemotherapy is used to improve survival in patients with metastases to regional lymph nodes demonstrated by routine histopathology with no other evidence of spread. The ability to identify metastatic disease at an earlier stage could be of considerable benefit in directing adjuvant therapy to patients at high risk of relapse who are not identified by current methods. Several techniques have been developed for the detection of MRD, including immunohistochemical and molecular methods, however their role in clinical practise is not yet established. The purpose of this paper is to review these techniques and their potential clinical use in the management of CRC.
Open Access
The morphological changes of exocrine pancreas in chronic pancreatitis
(Murcia : F. Hernández, 1999) Ashizawa, N.; Niigaki, M.; Hamamoto, N.; Kaji, T.; Katsube, T.; Sato, S.; Endoh, H.; Hidaka, K.; Watanabe, M.; Kinoshita, Y.
The following changes were found by either light or electron microscopic observation of the pancreas in spontaneously developed chronic pancreatitis models (WBNIKob rats, spontaneously hypertensive rats, and rats with common bile-pancreatic duct stones) and in experimental models of chronic pancreatitis (alcoholic pancreatitis, ischemic pancreatitis, and obstructive pancreatitis): 1) the units of lobules, which were constituted by acinar cell deletion, ductular proliferation, and fibrosis; and 2) tortuous or helical ductal channels of pancreatic ducts with periductal fibrosis, which had many crater-like depressions and very long cilia in their inner surface. These are considered to be the results of obstructive pancreatitis, which are caused by the reactions of defensive factors against the increase of pancreatic duct pressure, including the apoptosis of acinar cells, the hyperplasia and hypertrophy of duct cells, a tighter junctional complex of duct cells, and periductal fibrosis.
Open Access
Cytoskeletal proteins connecting intermediate filaments to cytoplasmic and nuclear periphery
(Murcia : F. Hernández, 1999) Djakovic-Svajcei, K.
Intermediate filaments (IFS), together with microtubules and microfilaments build up the cytoskeleton of most eukaryotic cells. Cytoplasmic IFS form a dense filament network radiating from the nucleus and extending to the plasma membrane. The association between the cytoplasmic and nuclear surfaces appears to provide a continuous link important for the organisation of the cytoplasm, for cellular communication, and possibly for the transport into and out of the nucleus. Cytoplasmic IFS approach the nuclear surface, thin fibrils seem to connect the IFS with the nuclear pore complexes and a direct interaction of cytoplasmic IFS with the nuclear lamin B has been observed by in vitro binding studies. However, none of the components that cross-link IFS to the nucleus has been unambiguously identified. Furthermore, if a direct interaction between cytoplasmic IFS and the nuclear lamin B occurs in vivo, the question of how cytoplasmic IFS get access to the nuclear interior remains to be resolved. The association of IFS with the plasma membranes involves different components, some of which are cell type specific. Two specialised complexes in epithelia1 cells: the desmosome and the hemidesmosome, serve as attachment sites for keratin filaments. Desmoplakin is considered as the cross-linking component of IFS to the desmosomal plaque, whereas BPAGl (bullous pemphigoid antigen) would cross-link IFS at the hemidesmosomal plaque. In other cell types the modality of how IFS are anchored to the plasma membrane is less well understood. It involves different components such as the spectrin based membrane skeleton, ankyrin, myosin, plectin and certainly many other still unravelled partners. Association between the IFS and cellular membranes plays an important role in determining cell shape and tissue integrity. Thus, the identification and characterisation of the components involved in these interactions will be crucial for understanding the function of intermediate filaments.
Open Access
Cytokeratin expression patterns in normal and malignant urothelium, a review of the biological and diagnostic implications
(Murcia : F. Hernández, 1999) Southgate, J.; Harnden, P.; Trejdosiewicz, L.K.
The cytokeratins are the intermediate filament proteins characteristic of epithelial cells. In human cells, some 20 different cytokeratin isotypes have been identified. Epithelia1 cells express between two and ten cytokeratin isotypes and the consequent profile which reflects both epithelial type and differentiation status may be useful in tumour diagnosis. The transitional epithelium or urothelium of the urinary tract shows alterations in the expression and configuration of cytokeratin isotypes related to stratification and differentiation. In transitional cell carcinoma, changes in cytokeratin profile may provide information of potential diagnostic and prognostic significance. The intensification of immunolabelling with some CK8 and CK18 antibodies may underly an active role in tumour invasion and foci of CK17-positive cells may represent proliferating populations. Loss of CK13 is a marker of grade and stage and de novo expression of CK14 is indicative of squamous differentiation and an unfavourable prognosis. However, perhaps the most important recent finding is the demonstration that a normal CK20 expression pattern is predictive of tumour non-recurrence and can be used to make an objective differential diagnosis between transitional cell papilloma and carcinoma. This review will consider cytokeratin expression in urothelium and discuss the application of cytokeratin typing to the diagnosis and prognosis of patients with TCC.
Open Access
Neutrophils as a source of cytokines in inflammation
(Murcia : F. Hernández, 1999) Matsukawa, A.; Yoshinaga, M.
The recruitment of neutrophils into inflammatory foci is a fundamental process observed in inflammation. The function of neutrophils has long been regarded only as an effector cell that kills the invading pathogens. Recent evidence has demonstrated that neutrophils are capable of producing inflammatory cytokines. The findings are, however, mainly based on the findings obtained in vitro. It has not been fully elucidated if neutrophils could synthesize and secrete cytokines in vivo. Animal models of inflammation are essential to address the issue and provide insight into the involvement of neutrophils in producing cytokines.
Open Access
Effects of long-term treatment with ethanol on the ultrastructure of the golden hamster parathyroid gland
(Murcia : F. Hernández, 1999) chen, H.; Hayakawa, D.; Emura, S.; Tamada, A.; Jamali, M.; Ozawa, Y.; Taguchi, H.; Yano, R.; Ohtake, N.; Shoumura, S.
The ultrastructure of the parathyroid gland in golden hamsters after long-term treatment with ethanol was studied. Male hamsters of experimental groups were given ethanol at the concentration of 7% for 3 and 5 months with food and water freely available. In the ethanol-treated hamsters, the Golgi complexes associated with many prosecretory granules were well developed and many secretory granules were located near the plasma membrane as compared with those of the control animals. Exocytotic events were observed in 5-month-treated animals. These findings suggest that the secretory activity of the parathyroid gland is stimulated after long-term treatment with ethanol.
Open Access
Brefeldin A influences the cell surface abundance and intracellular pools of low and high ouabain affinity Na+, K+-ATPase cx subunit isoforms in articular chondrocytes
(Murcia : F. Hernández, 1999) Mobasheri, A.
The catalytic a isoforms of the Na+, K+- ATPase and stimuli controlling the plasma membrane abundance and intracellular distribution of the enzyme were studied in isolated bovine articular chondrocytes which have previously been shown to express low and high ouabain affinity a isoforms (a1 and a 3 respectively; al>>a3). The Naf, K+-ATPase density of isolated chondrocyte preparations was quantified by specific 3 ~ - ouabain binding. Long-term elevation of extracellular medium [Na+] resulted in a significant (31%; p<0.05) upregulation of Na+, K+-ATPase density and treatment with various pharmacological inhibitors (Rrefeldin A, monensin and cycloheximide) significantly @<0.001) blocked the upregulation. The subcellular distribution of the NaC, K+-ATPase a isoforms was examined by immunofluorescence confocal laser scanning microscopy which revealed predominantly plasma membrane immunostaining of a subunits in control chondrocytes. In Brefeldin A treated chondrocytes exposed to high [Na+], Na+, K+-ATPase a isoforms accumulated in juxta-nuclear pools and plasma membrane Na+, K+- ATPase density monitored by 3~-ouaba inb inding was significantly down-regulated due to Brefeldin A mediated disruption of vesicular transport. There was a marked increase in intracellular a 1 and a3 staining suggesting that these isoforms are preferentially upregulated following long-term exposure to high extracellular [Na+]. The results demonstrate that Na+, K+-ATPase density in chondrocytes is elevated in response to increased extracellular [Na+] through de novo protein synthesis of new pumps containing a 1 and a 3 isoforms, delivery via the endoplasrnic reticulum- Golgi complex constitutive secretory pathway and insertion into the plasma membrane.
Open Access
Ultrastructural and biochemical analysis of epidermal xanthophores and dermal chromatophores of the teleost Sparus aurata
(Murcia : F. Hernández, 1999) Ferrer, C.; Solano, F.; Zuasti, A.
We have studied the pigmentary system of the teleost Sparus aurata skin by electron microscopy and chromatographic analysis. Under electron microscopy, we found the dermis to contain the three major types of recognized chromatophores: melanophores, xanthophores and iridophores. Melanophores were more abundant in the dorsal region, whereas the iridophores were more abundant in the ventral region. The most important discovery was that of epidermal xanthophores. Epidermal xanthophores were the only chromatophores in the epidermis, something only found in S. azirara and in a teleost species living in the Antartic sea. In contrast, the biochemical analysis did not establish any special characteristics: we found pteridine and flavin pigments located mostly in the pigmented dorsal region. Riboflavin and pterin were two of the most abundant coloured pigment types, but other colourless pigments such as xanthopterin and isoxanthopterin were also detected.
Open Access
Epidermal growth factor receptor EGFR biology and human oral cancer
(Murcia : F. Hernández, 1999) Todd, R.; Wong, D.T.W.
Dysregulation of the epidermal growth factor receptor (EGFR) is one of the most frequently studied molecular events leading to oral carcinogenesis. Overexpression of EGFR is a common event in many human solid tumors. Elevated levels of EGFR mRNA in human cancer occur with and without gene rearrangement. Structural alterations in the receptor can also result in the dysregulation of the EGFR pathway. EGFR overexpression without gene re-arrangement is frequently observed in human oral cancers. However, little is known whether structural alterations in the receptor or perturbations in the EGFR pathway contribute to oral carcinogenesis. Several preliminary studies suggest that EGFR-targeted therapeutic approaches might be successful in controlling oral cancer.
Open Access
Cholecystokinin, acting through the A receptor subtype, stimulates the proliferative activity of adrenocortical cells and thymocytes in the ra
(Murcia : F. Hernández, 1999) Malendowicz, L.K.; Tretjer, M.; De Caro, Raffaelle; Jedrzejczak, N.; Brelinska, R.; Markowska, A.; Nussdorfer, G.G.; Nowak, M.
Cholecystokinin (CCK) is a multifunctional regulatory peptide, which acts through two main subtypes of receptors, named CCK-A and CCK-B. Evidence indicates that CCK modulates cell proliferation in various tissues in a paracrine manner, and proofs are available of the presence of CCK in both adrenal glands and thymus. Hence, we have investigated the possible mitogenic action of this peptide on these two tissues, by evaluating the %o of metaphase-arrested cells after vincristin injection (mitotic index). The systemic administration of CCK (three subcutaneous injections of 20 nmollkg, 28, 16 and 4 h before the sacrifice) increased the mitotic index in both the outer adrenal and thymus cortexes of immature (20-day-old) rats and the enucleated adrenal gland of adult (2-month-old) animals at day 5 and 8 of regeneration. The simultaneous administration of equimolar doses of a selective CCK-A receptor antagonist blocked the effect of CCK, while a CCK-B antagonist was ineffective. These findings indicate that CCK exerts a marked CCK-A-mediated proliferogenic effect on both adrenal cortex and thymus in the rat, the physiological relevance of which, however, remains to be demonstrated. In fact, the administration of the CCK-A antagonist alone was ineffective, thereby casting doubts on the role played by endogenous CCK in the maintenance and stimulation of adrenal and thymus growth.