Histology and histopathology Vol.18, nº 3 (2003)

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Open Access
Cell populations in the pineal gland of the viscacha (Lagostomus maximus). Seasonal variations
(Murcia : F. Hernández, 2003) Cernuda-Cernuda, R.; Piezzi, R.S.; Domínguez, S.; Alvarez-Uría, M.
Pineal samples of the viscacha, which were taken in winter and in summer, were analysed using both light and electron microscopy. The differences found between the two seasons were few in number but significant. The parenchyma showed two main cell populations. Type I cells occupied the largest volume of the pineal and showed the characteristics of typical pinealocytes. Many processes, some of which were filled with vesicles, could be seen in intimate contact with the neighbouring cells. The presence in the winter samples of “synaptic” ribbons and spherules, which were almost absent in the summer pineals, suggests a seasonal rhythm. These synaptic-like structures, as well as the abundant subsurface cisterns present in type I cells, appeared as basic differential features which allowed these cells to be distinguished from type II cells. These latter cells, which can be classified as interstitial cells, showed some other distinguishing features, such as irregular-shaped nuclei, abundant deposits of glycogenlike particles and structures of unknown function consisting of concentric cisterns surrounding a dense body. In the summer, interstitial cells displayed numerous large round bodies, which contributed to increase the cellular volume slightly. Regarding other constituents, like glial cell processes, vessels of nonfenestrated endothelium and sympathetic innervation, no qualitative differences were observed between the two seasons studied. We have presented here some morphological evidences of the circannual rhythm of the viscacha pineal, as well as ultrastructural criteria for distinguishing the main cell populations of this organ, which could be useful for studies carried out in other mammals.
Open Access
Lectin binding in the human foetal testis
(Murcia : F. Hernández, 2003) Gheri, G.; Vannelli, G.B.; Marini, M.; Zappoli Thyrion, G.D.; Sgambati, E.
In the present study we have investigated the oligosaccharidic content of the glycoconjugates within the human foetal testis starting from its earliest differentiation phase (8, 10 and 12 weeks of gestation). To this purpose we have used a battery of six horseradish peroxidase-labelled lectins (SBA, PNA, WGA, UEAI, LTA and ConA). We have obtained a complete distributional map of the sugar residues of the glycoconjugates in the coelomic mesothelium, tunica albuginea, pre-Sertoli cells, pre-gonocytes, Leydig cells, basement membrane of the sex cords, interstitial tissue, mastocytes and endothelial cells of the capillary vessels. Since the beginning of the testis differentiation phase the cells of the coelomic mesothelium showed a large amount of sugar residues. In the pre-Sertoli cells and in the pre-gonocytes a role played as structural molecules by some oligosaccharides could be hypothesized. Dgalactose-( ß1?3)-N-acetyl-D-galactosamine, sialic acid, N-acetyl-D-glucosamine and a-D-mannose could be involved in inducing and maintaining the cellular activity of the Leydig cells.
Open Access
The pathobiologic spectrum of Schwannomas
(Murcia : F. Hernández, 2003) Kurtkaya-Yapicier, O.; Scheithauer, B.W.; Woodruff, J.M.
In terms of their morphology, clinical associations and behavior, peripheral nerve sheath tumors are among the most varied of human neoplasm. Not surprisingly, such tumors are subject to frequent misdiagnosis. This is particularly true of the spectrum of schwannomas which include: a) conventional schwannoma, a histologically benign tumor which, on occasion, is destructive of surrounding osseous structures, b) the relatively recently described cellular schwannoma, a tumor that histologically simulates malignant peripheral nerve sheath tumor (MPNST), c) plexiform schwannoma which, particularly in cellular form and when occurring in childhood, simulates MPNST, and d) melanotic schwannoma which is often mistaken for melanoma. The psammomatous form of the latter is often associated with Carney complex, a rare heritable disorder that: a) includes cutaneous lentigines, b) myxomas of skin, subcutaneous tissue, and heart, c) and endocrine neoplasms. The tendency to misdiagnose schwannomas and to overestimate their grade makes schwannomas worthy of note. Herein, we discuss the four major schwannoma variants, their essential clinicopathologic features, and differential diagnosis. The distinction from MPNST is given particular attention.
Open Access
Interleukin-7 (IL-7) and IL-7 receptor (IL-7R) signalling complex in human solid tumours
(Murcia : F. Hernández, 2003) Al-Rawi, M.A.A.; Mansel, R.E.; Jiang, W.G.
Interleukin-7 (IL-7) plays an important role in the normal development and maintenance of the human immune system. Its effects are mediated via its receptor, IL-7R. Ligand-receptor engagement results in a cascade of phosphorylation events mediated by various molecules including the Janus kinases (Jak1 and Jak3), PI3-kinase, Stats (signal transducers and activators of transcription) and other molecules. The activation of IL- 7 signalling pathway results in survival, proliferation, differentiation and maturation of haematopoietic cells including B and T lymphocytes. Although the relationship of IL-7 with the development and differentiation of some haematological cancers like leukaemias and lymphomas is well recognised, little is known about it involvement with solid tumours. There are several studies that have revealed IL-7/IL-7R expression in epithelial systems and some human solid epithelial tumours. Furthermore, IL-7 can be produced by some human tumour cells and involved in tumour development and progression. In this review article we have summarised the main biological activities of IL-7 and its downstream signalling complex in relation to some human solid malignancies.
Open Access
RNA is closely associated with human mast cell lipid bodies
(Murcia : F. Hernández, 2003) Dvorak, A. M.; Morgan, E.S.; Weller, P.F.
Both novel and multiple ultrastructural studies based on different principles show relationships of cytoplasmic lipid bodies and ribonucleic acid (RNA) of potential importance to RNA metabolism in human mast cells. The methods include general ultrastructural morphological observations, imaging of RNA with an EDTA regressive stain, imaging of the incorporation of radio labeled uridine by ultrastructural autoradiography, postembedding immunogold labeling of uridine, ribosomes and small nuclear ribonuclear proteins and ultrastructural in situ hybridization detection of poly(A)- positive messenger RNA. Altogether these studies implicate human mast cell lipid bodies in RNA metabolism and are analogous to earlier similar studies which showed that human mast cell granules also curtain RNA.
Open Access
Chromosomal instability and human hepatocarcinogenesis
(Murcia : F. Hernández, 2003) Nishida, N.; Nishimura, T.; Ito, T.; Komeda, T.; Fukuda, Y.; Nakao, K.
Recently, many studies have identified losses and gains of several chromosomal loci in human hepatocellular carcinoma (HCC) with fine microsatellite analysis and comparative genomic hybridization. Although distribution of aberrant chromosomal arms differs among HCCs, loss of 1p, 4q, 6q, 8p, 9p, 10q, 13q, 16q and 17p, and gain of 1q, 6p, 8q, 17q and 20q have been recurrently reported, and loss of 4q and 16q seems to occur preferentially in hepatitis B virus-related HCCs. Accumulation of these aberrant chromosomal regions is associated with tumor progression, and some chromosomal aberrations, such as loss of 1p, are frequently identified in well-differentiated HCCs and also detected even in dysplastic nodule and cirrhotic nodule. This evidence suggests that chromosomal instability (CIN) emerges at an early stage during hepatocarcinogenesis and is successively inherent to tumor cells, resulting in acquisition of malignant phenotype. The molecular basis of CIN is beginning to be explored; however, several mechanisms may be involved for CIN of HCC.
Open Access
Lectin binding patterns in normal canine endometrium and in bitches with pyometra and cystic endometrial hyperplasia
(Murcia : F. Hernández, 2003) Leitner, M.; Aurich, J.E.; Galabova, G.; Aurich, C.; Walter, I.
Cystic endometrial hyperplasia (CEH) and pyometra in the bitch are dioestral syndromes, supposed to be caused by hormonal disturbances and changes in endometrial steroid hormone receptor levels. Histologically, the endometria show cystic dilated glands and, if bacteria succeed in invading the uterus, pyometra may develop in the following metoestrus. In this study, lectin histochemistry was performed on paraffin sections to compare carbohydrate expression of uterine glands and surface epithelium in healthy dogs and in dogs with CEH and pyometra. Lectin binding is a useful tool to identify glycoconjugates, especially of the glycocalyx, which has essential functions in the endometrium during reproduction. Uterine tissue was obtained from 18 healthy bitches in metoestrus or anoestrus and 18 bitches with a clinical diagnosis of CEH or pyometra. Normal endometria showed cycle-dependent changes in SBA, PNA, HPA and UEA binding during metoestrus and anoestrus. LCA did not show cycle-dependent changes and WGA bound to Golgi regions in the apical parts of surface epithelial cells only in metoestrous. Endometria with inflammatory alterations lost cycle-specific lectin binding patterns and, with increasing severity of pathological changes, showed a marked decrease in binding intensity to the glandular and surface epithelial glycocalyx and secretions. In dogs with CEH, unaltered glands with generally strong lectin binding to the glycocoalyx and Golgi regions were found adjacent to altered glands. The decrease of lectin binding in pyometra cases is supposed to be a result of glandular exhaustion after cystic hyperplasia. In addition, bacterial adhesion to sugar residues on the uterine surface epithelium might impede lectin binding.
Open Access
The influence of different fibrous supplements in the diet on ruminal histology and histometry in veal calves
(Murcia : F. Hernández, 2003) Di Giancamillo, A.; Bosi, G.; Arrighi, S.; Savoini, G.; Domeneghini, C.
The aim of this study was to determine whether the administration of four different solid feeds would influence selected morphological and morphofunctional aspects of the rumen mucosa in veal calves. The fibrous supplementation of the liquid diet of veal calves has been provided by recent EU formulation (EC Council Directive 91/629/1991; EC Council Directive 97/2/1997). Twenty-five Holstein calves were assigned to either exclusively liquid diet (milk replacer, control), or pelleted feed, corn silage, extruded feed, dried corn silage. The morpho-functional effects of the fibrecontaining diets were examined evaluating histological and histometrical characteristics of ruminal mucosa after the slaughter of calves. There were slight to severe histological abnormalities in the rumens of all animals examined. The severe histological abnormalities were present in calves given pelleted feed, corn silage, and extruded feed. Dried corn silage caused less ruminal damage. We found that the length and epithelial thickness of ruminal papillae were higher in control veal calves than in dietary fibre-supplemented animals. The results of the present study, even if partially, support the EU prescription in the use of fibre diets in veal calves as integration of the traditional milk replacer diet.
Open Access
Understanding the role of the cytoskeleton inthe complex regulation of the endothelial repair
(Murcia : F. Hernández, 2003) Lee, J.S.Y.; Gotlieb, A.I.
Actin microfilaments and microtubules are important cytoskeletal proteins that regulate endothelial repair through alterations in cell shape and through regulation of cell migration following wounding of the endothelium. Upstream pathways have been identified in the regulation of actin and microtubule organization, especially small GTPases. Recently, there have been numerous proteins suggested to be capable of regulating interaction between microtubules and microfilaments to mediate microtubule regulation of endothelial repair, an important process in limiting injury to the artery wall and in reducing the extent of arterial disease. If disrupted, a rapid repair mechanism is important in reestablishing the integrity of the endothelium in order to reestablish its function as a macromolecular barrier, a thromboresistant surface, and a biologically active tissue. Strategies to improve repair should alter the pathobiology of the atherosclerotic plaque and thus improve the prognosis of patients with atherosclerosis.
Open Access
Upregulation of vascular endothelial growth factor (VEGF) in the retinas of transgenic mice overexpressing interleukin-1ß (IL-1ß) in the lens and mice undergoing retinal degeneration
(Murcia : F. Hernández, 2003) Vinores, S.A.; Xiao, W.H.; Zimmerman, R.; Whitcup, S.M.; Wawrousek, E.F.
IL-1ß is a pro-inflammatory agent associated with angiogenesis and increased vascular permeability. To determine whether IL-1ß elicits these responses through an upregulation of VEGF, transgenic mice that overexpress IL-1ß in the lens were evaluated at various time points for the localization of VEGF, the location and extent of blood-retinal barrier (BRB) breakdown, and the origin and extent of neovascularization (NV). In homozygous and heterozygous transgenic mice, but not controls, intense VEGF immunoreactivity was scattered throughout the retina at postnatal days 5-7 (P5-7), just after the onset of inflammatory cell infiltration. VEGF staining in the retina remained widespread, but weak from P9-15. Beginning at P15, the intensity of VEGF immunoreactivity achieved a second peak, which it maintained through adulthood. This peak coincided with significant retinal destruction due to massive inflammation. The onset of BRB breakdown coincided with the upregulation of VEGF (P5-7) and widespread BRB breakdown was demonstrated from about P9. From P9-12, aggregates of cells positive for Griffonia simplicifolia isolectin-B4, a marker for vascular endothelial cells, formed on the retinal surface. These cells migrated into the retina at P12-15 with the more superficial cells forming a network of vessels and the deeper cells remaining in small clusters, thus demonstrating that NV occurs much later than BRB breakdown. Non-transgenic FVB/N mice, which undergo retinal degeneration beginning at about P9, also demonstrate the latter peak of VEGF upregulation and the accompanying BRB breakdown, but not the early upregulation. VEGF immunostaining of transgenic and non-transgenic mouse retinas was eliminated by preincubation of the VEGF antibodies with VEGF peptide. The data suggest that the early peak of VEGF upregulation (P5-7) and its accompanying BRB breakdown is due to IL-1ß expression and is likely to be dependent on inflammatory cell infiltration. The latter peak appears to be related to retinal destruction.
Open Access
An electron microscopic and biochemical study of the effects of propranolol on the glycogen autophagy in newborn rat hepatocytes
(Murcia : F. Hernández, 2003) Kotoulas, Othon B.; Kalamidas, Stefanos; Miles, P.; Hann, A.C.
The effects of propranolol on the glycogen autophagy in newborn rat hepatocytes were studied by using biochemical determinations, electron microscopy and morphometric analysis. Propranolol lowered the liver cyclic AMP and cyclic AMP-dependent protein kinase activity. It also decreased the formyl-methionylleucyl- phenylalanine (FMLP)-inhibitable Ca2+-ATPase activity including lysosomal calcium uptake pump. The normal postnatal increase in the volume of autophagic vacuoles and the activity of acid glycogen-hydrolyzing alpha glucosidase were inhibited. Also, the degradation of glycogen inside the autophagic vacuoles was apparently inhibited. The activity of acid mannose 6- phosphatase was increased. These findings indicate that propranolol influences several steps in the sequence of events leading to the breakdown of glycogen in the autophagic vacuoles of newborn rat hepatocytes. This supports our previous studies suggesting that cyclic AMP regulates glycogen autophagy.
Open Access
In vivo cellular uptake of bismuth ions from shotgun pellets
(Murcia : F. Hernández, 2003) Stoltenberg, M.; Locht, L.; Larsen, Agnete; Jensen, D.
Shotgun pellets containing bismuth (Bi) are widely used and may cause a rather intense exposure of some wild animals to Bi. A Bi shotgun pellet was implanted intramuscularly in the triceps surae muscle of 18 adult male Wistar rats. Another group of 9 animals had a Bi shotgun pellet implanted intracranially in the neocortex. Eight weeks to 12 months later the release of Bi ions was analysed by autometallography (AMG) of tissue sections from different organs (brain, spinal cord, kidney, liver, testes). In the group with intramuscular Bi shotgun pellets no AMG staining could be found for the first 2-4 months; 6 months after exposure Bi was traced in the kidney. Twelve months after the implantation the kidneys were heavily loaded and Bi was also traced in testosterone-producing Leydig cells, in glial cells and in neurons of brain and spinal cord. In the central nervous system (CNS) motor neurons were the most loaded. In rats with intracranially implanted shotgun pellets a massive uptake of Bi was observed involving both glia and neurons throughout the brain. The cells close to the shotgun pellet had the highest uptake. The animals showed a pronounced Bi uptake in the ependyma cells lining the ventricular system and in the cubic epithelia covering the choroid plexus. Dissemination of Bi ions to the rest of the body was demonstrated by AMG tracing of Bi accumulations in the tubular cells of the kidney. These findings emphasize that metallic Bi, including shotgun pellets, represents sites of intense Bi pollution if implanted or shot into a living organism, and further that such metallic Bi bodies, if they enter the CNS, cause a spread of Bi ions throughout it.
Open Access
Ultrastructural evaluation of the effect of endosulfan on mice kidney
(Murcia : F. Hernández, 2003) Çaglar, Y.; Kaya, M.; Belge, E.; Mete, U.O.
In this study, the effect of the endosulfan on mice kidney was investigated at ultrastructural level. Moreover, biochemical analyses (G6PD, CAT, SOD, GSH and MDA) were determined in supernatant of kidney tissue. Endosulfan (13mg/kg/day body weight) was administered orally to mices via intragastric-during 10 days. The presence of mitochondrial degeneration in cytoplasm of proximal convoluted tubule cells were a striking feature. Furthermore, there was lipofuscin granules and membranous structures in some of proximal convoluted tubule cells. In some glomeruli, ultrastructural changes such as fusion in pedicels and focal thickening at glomerular basal membrane were seen. There were cytoplasmic bulges in some distal convoluted tubule cells. The biochemical results of the experimental group were significant when compared to the control. The effect of the endosulfan was mainly on the proximal convoluted tubule cells. Morever, the other parts of the nephron were effected. Thus, this degeneration in kidney may be thought that oxidative stress may play a role to the mediator in changing configuration of cell membrane and seem to account for the morphologic alteration of kidney.
Open Access
Cisplatin induced gamma-glutamyltransferase up-regulation, hypertrophy and differentiation in astrocytic glioma cells in culture
(Murcia : F. Hernández, 2003) Mares, V.; Lisá, V.; Malík, R.; Kozáková, H.; Sedo, A.
Gamma-glutamyltransferase (GGT) hydrolyses gamma-glutamylated peptides, including glutathione and transports amino acids into the cells. The enzyme is up-regulated in some tumors, especially those with a higher degree of malignancy and resistance to cytostatics. In this study we examined the effects of Cisplatin (1.6 x 10-5M) on the activity of GGT in astrocytic C6 glioma cells in cultures monitored for growth, morphology and differentiation. Initially (24 h), the drug inhibited cell division and later (96 h), it caused apoptotic death of about half of the population. The more resistant and surviving cells became hypertrophic and more differentiated, as indicated by their larger size and higher protein content, including the maturationspecific GFAP. In addition, the activity of GGT was significantly elevated in these cells at 48 h and onwards. At 96 h, the biochemically determined enzyme activity was between 230% and 330% above the controls. Compared to the protein content, the GGT activity started to increase later (48 h) but it grew steeper towards 72-96 h. Similarly, histochemical analysis revealed a manifold increase in the number of GGT+ cells in the population and higher intensity of staining per cell from at 48 h and onwards. The study showed that the transformed astrocytic cells can up-regulate GGT activity as part of an adaptation and/or, survivalenhancing reaction triggered by Cisplatin.
Open Access
T cell regulation of the immune response to infection in periodontal diseases
(Murcia : F. Hernández, 2003) Yamazaki, K.; Yoshie, H.; Seymour, G.J.
Although T cells have been implicated in the pathogenesis and are considered to be central both in progression and control of the chronic inflammatory periodontal diseases, the precise contribution of T cells to the regulation of tissue destruction has not been fully elucidated. Current dogma suggests that immunity to infection is controlled by distinct T helper 1 (Th1) and T helper 2 (Th2) subsets of T cells classified on the basis of their cytokine profile. Further, a subset of T cells with immunosuppressive function and cytokine profile distinct from Th1 or Th2 has been described and designated as regulatory T cells. Although these regulatory T cells have been considered to maintain selftolerance resulting in the suppression of auto-immune responses, recent data suggest that these cells may also play a role in preventing infection-induced immunopathology. In this review, the role of functional and regulatory T cells in chronic inflammatory periodontal diseases will be summarized. This should not only provide an insight into the relationship between the immune response to periodontopathic bacteria and disease but should also highlight areas of development for potentially new therapeutic modalities.
Open Access
Sunburn reaction in the dorsal skin of hypotrichotic WBN/ILA-Ht rats
(Murcia : F. Hernández, 2003) Okada, T.; Albarenque, S.M.; Yasoshima, A.; Malcotti, V.; Katayama, K.; Uetsuka, K.; Nakayama, Hiroyuki; Doi, K.
The dorsal skin responses to a single irradiation with a high-dose of UVB (10kJ/m2) were examined histologically and immunohistochemically in UVB-sensitive Wistar-derived hypotrichotic WBN/ILAHt rats (HtRs). Sunburn cells (SBCs) which were characterized by pyknotic nuclei and eosinophilic cytoplasm and had ultrastructual characteristics of apoptotic cells were first observed in the epidermis at 3 hours (h) after irradiation. The number peaked at 6 h, and then decreased rapidly. The expressions of p53 protein, which is known to be closely related to the formation of SBCs, and of p21 protein, which is one of the transcriptional target genes of p53, were immunohistochemically detected, and their labeling index (LI) in the epidermis peaked at 12 to 24 h (p53) or at 24h (p21) after irradiation. On the other hand, proliferating cell nuclear antigen (PCNA)-LI in keratinocytes was significantly lower than the control group at 6 h after irradiation and thereafter it increased and became significantly higher than the control group from 24 to 48 h. At 48 h, moderate hyperplasia with moderate numbers of mitotic keratinocytes was first observed in the epidermis. In the dermis, mild edema developed from 12 to 36 h and it accompanied mild lymphocyte infiltration at 36 h. Judging from the present results, it was suggested that some factors other than p53 might be involved in SBC formation, and that p53 might induce p21 protein and play an important role in cell growth arrest in keratinocytes after UVB irradiation.
Open Access
Modulatory role of IL10 in endothelial cell damage and platelet adhesion
(Murcia : F. Hernández, 2003) Gimeno, M.J.; Pascual, G.; García-Honduvilla, N.; Prieto, A.; Alvarez de Mon, M.; Bellón, J.M.; Buján, J.
This study explores the possibility of a regulatory role for cytokine IL-10 in platelet aggregation as an active vascular repair mechanism. Endothelial cells from human umbilical cord vein were cultured in the presence of different IL-10 concentrations (0-100 ng/ml). Platelet-rich plasma was then added to these cultures and allowed to act for 30 minutes. To rule out blood plasma involvement, washed platelets were also incubated with IL-10 (0-100 ng/ml). Changes in endothelial cell morphology were observed depending on the IL-10 concentration used; apoptotic cells appearing at the highest IL-10 concentration. Greatest platelet adhesion was noted at the highest IL-10 concentration. It was concluded that, in this in vitro model, low IL-10 levels do not affect cell viability or the pattern of platelet adhesion, but at high doses, this cytokine induces cell death and enhances platelet deposition.
Open Access
Gene products involved in metastasis of bladder cancer
(Murcia : F. Hernández, 2003) Davies, B.R.
Metastasis is usually responsible for mortality in patients suffering from muscle invasive bladder cancer. Whilst expression of a great number of genes and their protein products have been associated with metastasis and/or poor prognosis in bladder cancer, evidence that they actively drive the metastatic process, and hence make potentially good therapeutic targets, is often lacking. This is due to the limited number and application of effective animal models which reflect the pathogenesis of the human disease. In this review I will discuss the processes involved in metastasis, consider the established animal models of bladder cancer progression and metastasis, and review the evidence for a role of various gene products in this process. Consideration of clinical studies in conjunction with evidence from experimental animal models reveals that the tyrosine kinase receptor erbB1/EGFR, the calcium binding protein S100A4 and the the cell cycle arrest/apoptosis-inducing p53 protein are amongst the most promising targets for therapy against metastatic disease in patients with bladder cancer.
Open Access
Expression of hypoxia-inducible factor-1a (HIF-1a) in pituitary tumours
(Murcia : F. Hernández, 2003) Vidal, S.; Horvath, E.; Kovacs, K.; Kuroki, T.; Lloyd, R.V.; Scheithauer, B.W.
The present study was performed to investigate HIF-1a (hypoxia-inducible factor-1a) expression in a large number of immunohistochemically and ultrastructurally characterized surgically removed pituitary tumours. The potential relation of HIF-1a with outcome variables as well as the presence of HIF-1a expression in the tumours treated with dopamine agonists and octreotide, a long-acting somatostatin analogue was also investigated. HIF-1a immunoreactivity was confined to the nucleoplasm whereas the nucleoli were unconspicuous. The distribution of HIF-1a was evident in the tumours whereas normal adenohypophysial cells showed no HIF- 1a staining. HIF-1a expression was detected not only in the tumour cells but also in endothelial cells lining the blood vessels within the tumour. ACTH producing adenomas showed the lowest level of HIF-1a expression whereas pituitary carcinomas and GH producing adenomas had the highest counts. The statistical study demonstrated no significant correlation between HIF-1a expression, patient age, gender, tumour, size, invasiveness, cell proliferation rate and vascularity. These results suggest that the behaviour of pituitary tumours does not primarily depend of HIF-1a expression. Our study demonstrated an increase HIF-1a expression in bromocriptine treated PRL producing pituitary adenomas compared with untreated tumours but no increase in octreotide treated tumours.
Open Access
Lipid kinases play crucial and multiple roles in membrane trafficking and signaling
(Murcia : F. Hernández, 2003) Heath, C.M.; Stahl, P.D.; Barbieri, M.A.
Phosphotidylinositols (PIs) are known to play an essential role in membrane trafficking and signaling transduction. PIs serve multiple functions, such as recruitment of cytosolic proteins with PI phosphate (PIP) binding domains and modification of the physical properties of the membranes in which they reside. As substrates for phosphoinositide-specific lipases they function as a switch point in phosphoinositide metabolism. Recent work with epidermal growth factor receptor (EGFR) and colony stimulating factor-1 receptor (CSFR) has identified a possible connection between endocytosis of activated receptors and type-1 phosphatidylinositol-4-phosphate-5-kinase. Furthermore, serine/tyrosine phosphorylation of phosphatidylinositol- 4-phosphate-5-kinase seems to be essential for its activities. Indeed, one of the products of the phosphatidylinositol-4-phosphate-5-kinases, PIP2, has been shown to be involved in multiple steps of endocytosis, including the assembly of the clathrin coat, regulation of adaptor proteins, and production of endocytic vesicles via the regulation of dynamin. The discussion in this review focuses primarily on receptors with intrinsic enzymatic activity, specifically on receptor tyrosine kinases (RTKs). We will discuss their structure; mechanism of action and potential role in membrane trafficking and/or signaling through the regulation of phosphatidylinositol phosphate kinases.