Histology and histopathology Vol.25, nº2 (2010)
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- PublicationOpen AccessTubular epithelial cell and podocyte apoptosis with de novo sirolimus based immunosuppression in renal allograft recipients with DGF(Murcia : F. Hernández, 2010) Munivenkatappa, R.; Haririan, A.; Papadimitriou, J.C.; Drachenberg, C.B.; Dinits-Pensy, M.; Klassen, D.K.Sirolimus is associated with prolongeddelayed graft function (DGF) following renaltransplantation and exacerbation of proteinuria. Weassessed renal allograft biopsies from DGF patientstreated with de novosirolimus (n = 10) for renal tubularcell and podocyte apoptosis and expression of activatedcaspase-3, Bcl-2, and mTOR and compared them tobiopsies from DGF patients not receiving sirolimus (n =15). Both groups received mycophenolate mofetil,prednisone and antibody induction. Apoptosis wasassessed using terminal deoxynucleodidyl transferasemediated dUTP nick end labeling (TUNEL) staining.Caspase-3, Bcl-2, and mTOR expression were assessedby immunohistochemistry. Sirolimus treated patients had334±69 TUNEL positive cells per 5 high power fieldscompared to 5.5±2.9 TUNEL positive cells in controlpatients (p<0.001). The number of TUNEL positive cellscorrelated with tubular architectural disruption.Expression of activated caspase-3, Bcl-2, or activatedmTOR did not differ between groups. 60% of biopsiesfrom sirolimus treated patients compared to 7% ofbiopsies from controls showed diffuse podocyteapoptosis (p = 0.007). There was no podocyte expressionof activated mTOR, activated caspase-3, or Bcl-2 ineither group. These data suggest that DGF patientstreated with sirolimus have increased renal tubular cellapoptosis and podocyte apoptosis.
- PublicationOpen AccessThe distribution of vasotocin and mesotocinimmunoreactivity in the hypothalamic magnocellularneurosecretory nuclei of the Saharan herbivorous lizard,Uromastix acanthinurus Bell, 1825 (Sauria-Agamidae)(Murcia : F. Hernández, 2010) Barka-Dahane, Zohra; Bendjelloul, Mounira; Estabel, Jeanne; Exbrayat, Jean-MarieAn immunohistochemical study of themagnocellular neurosecretory nuclei was performed inthe hypothalamus of the desert lizard Uromastixacanthinurususing polyclonal antibodies againstarginine vasotocin (AVT), mesotocin (MST) andneurophysins I and II (NpI, NpII). AVT- and MST-immunoreactivities were localized in individual neuronsof the supraoptic, periventricular, and paraventricularnuclei and in scattered neurosecretory cells. Thesupraoptic nuclei (SONs) can be subdivided into rostral,medial and caudal portions. The rostral portion of theSONs was called the SON-ventral aggregation (V SON)because the neurosecretory neurons are present in theventral part of the hypothalamus along the optic chiasma(OC). Their perikarya and fibres were only AVT-ir. Themedial part of the SONs was constituted of two clustersof neurosecretory neurons located in the two lateral endsof the OC to form the SON-lateral aggregations (LSON). In the caudal end of the last one, some MST-irperikarya appeared. The caudal part of the SONs wasconstituted of a dorso-lateral aggregation (D SON) of ir-neurons spreading over the lateral forebrain bundle(LFB). AVT- and MST- perikarya were observed in thiscaudal portion of the SONs, AVT-ir neurons being morenumerous. AVTergic and MSTergic magnocellularneurons were present in the periventricular nuclei(PeVNs). Parvocellular and magnocellular AVT- andMST-ir were observed in the paraventricular nuclei(PVNs). The fibres emerging from the magnocellularneurons which belong to these nuclei and the scatteredcells ran along the hypothalamic floor and entered themedian eminence (ME) to end in the neural lobe ofhypophysis. As a rule, immunoreactivity was alsoobserved in all the regions of the forebrain withvasotocinergic and mesotocinergic perikarya and fibres.The immunoreactive distribution was similar to thatdescribed in other reptiles.
- PublicationOpen AccessNandrolone decanoate increases satellite cell numbers in the chicken pectoralis muscle(Murcia : F. Hernández, 2010) Allouh, Mohammed Z.; Rosser, Benjamin W.C.The anabolic androgenic steroid nandrolonedecanoate has minimal androgenic effects and, thus, iswidely used to induce muscle hypertrophy in bothpatients and athletes. Although increases in satellite cellnumbers and satellite cells giving rise to new myonucleiare associated with hypertrophy in many experimentalmodels, the relationship between nandrolone andsatellite cells is poorly understood. Here we test thehypothesis that nandrolone administration is associatedwith an increase in satellite cell numbers in muscle.Nandrolone was injected at weekly intervals for fourweeks into the right pectoralis muscle of female whiteleghorn chickens aged 63 days post hatch. Age/size/sexmatched control birds received saline injections. Thecontralateral pectoralis was excised for study from eachcontrol and nandrolone treated bird. An antibody againstPax7 and immunocytochemical techniques were used toidentify satellite cells. Nandrolone significantlyincreased mean pectoralis mass by approximately 22%,and mean fiber diameter by about 24%. All satellite cellindices that were quantified increased significantly inchicken pectoralis with administration of nandrolone.Nandrolone injected birds had on average higher satellitecell frequencies (#SC nuclei/all nuclei within basallamina), number of satellite cells per millimeter of fiber,and satellite cell concentrations (closer together).Myonuclei were further apart (less concentrated) innandrolone injected muscle. However, an overallincrease in myonuclear numbers was revealed by asignificantly greater mean number of myonuclei permillimeter of fiber in nandrolone injected muscle. Ourresults suggest that satellite cells may be key cellular vectors for nandrolone induced muscle fiberhypertrophy.
- PublicationOpen AccessExpression and distribution of the intermediate filament protein nestin and other stem cell related molecules in the human olfactory epithelium(Murcia : F. Hernández, 2010) Minovi, Amir; Witt, Martin; Prescher, Andreas; Gudziol, Volker; Dazert, Stefan; Hatt, Hanns; Benecke, HeikeThe olfactory epithelium (OE) is unique inregenerating throughout life and thus is an attractivetarget for examining neurogenesis. The nestin proteinwas shown to be expressed in the OE of rodents and issuggested to be essentially involved in the process ofregeneration. Here we report the expression anddistribution of nestin in the human OE at RNA andprotein level. Moreover, we analysed the expressionprofiles in dependence on age and olfactory capacity.After sinus surgery, biopsies were taken from theolfactory epithelium of 16 patients aged 20-80 yearswith documented differences in their olfactory function.Our studies revealed that nestin is constantly detectablein the apical protuberances of sustentacular cells withinthe human OE of healthy adults. Its expression is notdependent on age, but rather appears to be related to theolfactory function, as a comparison with specimensobtained from patients suffering either from persistentanosmia or hyposmia suggests. Particularly, in thecourse of dystrophy, often accompanied with impairedolfaction, nestin expression was occasionally decreased.Contrarily, the expression of the p75-NGFR protein, amarker for human OE basal cells, was not altered,indicating that at least in the tested samples olfactoryimpairment is not connected with abnormalities at thebasal cell level. These observations emphasize anessential role of nestin for the process of regeneration,and also highlight this factor as a candidate marker forsustentacular cells in the human olfactory epithelium
- PublicationOpen AccessAn overview on the diversity of cellular organelles during the germ cell cycle(Murcia : F. Hernández, 2010) Chuva de Sousa Lopes, Susana M.; Roelen, Bernard A.J.In mammals, germ cells undergo a longjourney from specification until sexual maturation.During this journey, which takes place during the entirelife cycle of mammals, the germ cells dynamicallychange their morphology, their expression profile andalso the number and character of their cellular bodies.The focus of this review will be the diversity of cellularorganelles present in the nucleus and cytoplasm at thedifferent phases of germ cell development. We discusshow these organelles associate and behave to form amultitude of bodies that have long been observed byscientists, and how their presence or absence is used tocharacterize different stages of germ cell development.These organelles include the female Barr body, polarbodies and Balbiani body; and the male sex body and chromatoid body. It is concluded thatcompartmentalization of organelles and molecules in thecytoplasm (in particular of mitochondria and RNAs) andof the sex chromosomes in the nucleus seems to beimportant for regulating germ cell developmentthroughout the life cycle
- PublicationOpen AccessBDNF function and intracellular signaling in neurons(Murcia : F. Hernández, 2010) Numakawa, Tadahiro; Suzuki, Shingo; Kumamaru, Emi; Adachi, Naoki; Richards, Misty; Kunugi, HiroshiBrain-derived neurotrophic factor (BDNF)and its receptor, TrkB, are broadly expressed in thedeveloping and adult mammalian brain. BDNF/TrkB-stimulated intracellular signaling is critical for neuronalsurvival, morphogenesis, and plasticity. It is well knownthat binding of BDNF to TrkB elicits variousintracellular signaling pathways, including mitogen-activated protein kinase/extracellular signal-regulatedprotein kinase (MAPK/ERK), phospholipase Cγ(PLCγ),and phosphoinositide 3-kinase (PI3K) pathways, andthat BDNF exerts biological effects on neurons viaactivation of similar mechanisms. In addition to TrkB, alow-affinity receptor p75 is also involved in neuronalsurvival and plasticity. BDNF affects neurons positivelyor negatively through various intracellular signalingpathways triggered by activation of TrkB or p75. From aclinical standpoint, roles of BDNF have been implicatedin the pathophysiology of various brain diseases. Thestress-induced steroid hormone, glucocorticoid, andBDNF are putatively associated with thepathophysiology of depression. Recent reports, includingour studies, demonstrate possible crosstalk betweenglucocorticoid- and BDNF/TrkB-mediated signaling.Here, we present a broad overview of the currentknowledge concerning BDNF action and associatedintracellular signaling as it relates to neuronal protection,synaptic function, and morphological change.Furthermore, understanding the secretion andintracellular dynamics of BDNF proteins is critical as thefate of secreted BDNF may contribute to differences inneuronal response
- PublicationOpen AccessContemporary approaches for processing and handling of radical prostactomy specimens(Murcia : F. Hernández, 2010) Sung, Ming-Tse; Cheng, LiangStandardized protocols for processing radicalprostatectomy specimens are critical for superior patientmanagement. It provides accurate information to theclinician in a reliable and consistent format to enhancepatient care and prognosis. In recent years, processingprotocols have been proposed by various authoritativegroups, with similar suggestions for most parts of thepractice guidelines; however, discrepancy in processingapproaches still exists. Standardization improves thequality and consistency of pathology reports. In thisreview article, we incorporate the processing schemesfor radical prostatectomy addressed in literature andpropose a comprehensively standardized approach toevaluate radical prostatectomy specimens.
- PublicationOpen AccessMorphometric study of healthy jejunal and ileal mucosa in adult and aged subjects(Murcia : F. Hernández, 2010) Trbojević-Stanković, Jasna B.; Milicevic, Novika M.; Milošević, Dragoslav P.; Despotović, Nebojša; Davidovic, Mladen; Erceg, Predrag; Bojic, Božidar; Bojic, Danijela; Svorcan, Petar; Protić, Marijana; Dapcevic, Branka; Miljković, Miloš D.; Milicevic, ŽivanaSmall intestine mucosa is often affected with malabsorptive, autoimmune and inflammatory pathological processes. However, morphometric data on the healthy human small intestine mucosa, especially ileum, are scarce. We aimed to obtain histoquantitative data on the healthy jejunal and ileal mucosa and assess the effects of gender and ageing on these parameters. Computer-aided morphometric analysis was performed on 24 jejunal and 25 ileal biopsy samples collected upon routine endoscopy screening of healthy persons with a family history of intestinal malignancy. Subjects were distributed in four groups according to age and sex: adult (<60 years) and elderly (>60 years) males, and adult (<60 years) and elderly (>60 years) females. Results were statistically analyzed with Mann-Whitney U test. Jejunal mucosal thickness was significantly reduced in elderly subjects (p<0.05), especially in elderly females compared to adult ones (p<0.05). Jejunal villi were significantly wider in adult than in the elderly subjects (p<0.05), whereas ileal villi were significantly wider in elderly compared to adult subjects (p<0.01) and in male compared to female subjects (p<0.05). No statistically significant differences were found in other histoquantitative parameters (mucosa epithelium height, crypt numerical density, villous height, crypts and villous perimeter, diameter and epithelium height) of jejunal and ileal mucosa. This study provides complete morphometric data on the healthy human jejunum and the first relevant data on the healthy ileal mucosa, thus representing a valuable morphometric reference for future histoquantitative studies of human small bowel mucosa in both healthy and disease affected individuals
- PublicationOpen AccessIn vitro antigen-specific cytotoxic T cell response against esophageal carcinoma cells induced by HPV18E7-transfected dendritic cells(Murcia : F. Hernández, 2010) Wu, Lin; Yang, Wei; Chen, Lin-Xin; Chen, Shen-Ren; Zhang, Jin-KunHuman Papillomavirus (HPV)-associatedesophageal carcinoma (EC) is a high incidence tumorworldwide. Dendritic cell (DC)-based tumor vaccine isconsidered an alternative therapy to treat EC. Here wedeveloped a DC-based vaccine by transfecting cordblood CD34+stem cell-derived DC with HPV18E7gene, observed its biological characteristics and theantigen-specific T-cell cytotoxicity on EC cells inducedby HPV18E7-DC in vitro. Our results showed that 1)HPV18E7 gene transfer did not change the typicalmorphology of mature DC, 2) the representativephenotypes of mature DC (CD80, CD86, and CD83)were highly expressed in HPV18E7- DC (81.6%, 80.5%,and 86.6%, respectively), 3) the expression level of18E7 protein in HPV18E7-DC was 47.5%, and 4) thespecific cytotoxicity against EC cells was significantlyhigher than that in controls (p<0.01). This studyindicates the possibility of a DC-based immunotherapyin HPV-associated EC.
- PublicationOpen AccessRecent progress in the etiopathogenesis of pediatric biliary disease, particularly Caroliâ s disease with congenital hepatic fibrosis and biliary atresia(Murcia : F. Hernández, 2010) Nakanuma, Yasuni; Harada, Kenichi; Sato, Yasunori; Ikeda, HirokoRecent progress in elucidating the etiopathogenesis of pediatric biliary diseases, particularly Caroli’s disease with congenital hepatic fibrosis (CHF) and biliary atresia (BA), is reviewed. The former is characterized by multiple saccular dilatations of the intrahepatic bile ducts. An animal model of this disease, the PCK rat, is being extensively studied. PCK rats and Calori’s disease with CHF belong to autosomal recessive polycystic kidney disease (ARPKD) with ductal plate malformation. Mutations of PKHD1 have been identified in ARPKD, and fibrocystin, a product of PKHD1 located in the cilia of bile ducts is lacking in the pathologic intrahepatic bile ducts of ARPKD. Disordered cell kinetics, including apoptosis of biliary epithelial cells (BECs), may be significantly related to ductal plate malformation, and laminin and type IV collagen were immunohistochemically reduced in the basement membrane of intrahepatic bile ducts of ARPKD, and such a reduction is an additional factor for the dilatation of bile ducts. Abundant connective tissue growth factor retained diffusely in heparan sulfate proteoglycan in the fibrous portal tracts are responsible for non-resolving hepatic fibrosis. In addition, pathologic BECs of ARPKD may acquire mesenchymal features and participate in progressive hepatic fibrosis by producing extracellular matrix molecules. In an animal model of BA, an initial virus-induced, T-cell mediated autoimmune-mediated cholangiopathy has been reported. In human BA, virus-induced apoptosis of BECs by a TNF-related apoptosis-inducing ligand followed by the progressive obliteration of bile ducts is also suggested, and epithelial mesenchymal transition of BECs induced by viral infection may be involved in the fibrotic process in sclerosing cholangitis. However, the role of viral infections in the affected tissues is controversial. Comprehensive and analytical studies of ARPKD and BA using human materials and animal models may lead to the clarification of their etiopathogenesis and open the way for new therapeutic strategies
- PublicationOpen AccessSmall cell carcinoma of the urinary bladder(Murcia : F. Hernández, 2010) Pant-Purohit, Mukta; López Beltrán, Antonio; Montironi, Rodolfo; MacLennan, Gregory T.; Cheng, LianSmall cell carcinoma of the urinary bladder(SCCUB) is a rare and aggressive cancer of the bladder.SCCUB is part of neuroendocrine family of tumors thataffect several organ systems including respiratory,gastrointestinal and male and female genitourinary tract.SCCUB affect males predominantly with common riskfactors include smoking, bladder calculi, bladdermanipulation, and chronic cystitis. Prognosis of SCCUBremains poor due to high metastatic potential and lack ofsymptoms in earlier stages of the disease. Pathogenesisof the disease is linked to loss of genetic material,hypermethylation of tumor suppressors and at timesamplification of the chromosomal regions carryingoncogenes. Majority of cases are treated with localresection of the tumor with neoadjuvant or adjuvantplatinum-based chemotherapy regimen. Radiationtherapy is used as alternative to radical cystectomy or aspalliative measure. This article provides epidemiology,molecular pathogenesis, histochemistry, and currentmanagement options for SCCUB. Furthermore wereviewed all recent studies involving advancement intargeted molecular therapy for neuroendocrine tumors.
- PublicationOpen AccessLectin-binding pattern of Senegalese sole Solea senegalensis (Kaup) testis(Murcia : F. Hernández, 2010) Desantis, S.; Zizza, S.; García-López, A.; Sciscioli, V.; Mañanos, E.; De Metrio, V.G.; Sarasquete, C.The localization and characterization of oligosaccharide sequences in the testis of Senegalese sole Solea senegalensis was investigated using 12 lectins in combination with KOH saponification and sialidase digestion (K-s). The interstitial compartment contained all the sugar residues investigated, those bearing oligosaccharides terminating with sialic acid (Neu5Ac) α2,3Galß1,4GlcNAc, Neu5AcGalNAcα1,3(LFucß1,2)Galß1,3/4GlcNAcß1 and GalNAcα1,3(LFuc1,2)Galß1,3/4GlcNAcß1 being more abundant in the medullar region than in the cortex. The melano-macrophage centres found in the interstitial compartment displayed glycans terminating with Galß1,3GalNAc. The basal lamina separating the germinal and interstitial compartments exhibited glycans with terminal/internal mannose, internal ßGlcNAc, and terminal Neu5Acα2,6Gal/GalNAc, and Neu5AcGalß1,3GalNAc, Galß1,3GalNAc (PNA), Galß1,4GlcNAc, GalNAc, αGal, and αL-Fuc. In the germinal compartment, the Sertoli cells expressed only glycans terminating with Neu5Acα2,3Galß1,4GlcNAc in the apical and supra-nuclear lateral surface of the spermatonial cysts located in the distal part of the seminiferous lobules. Primary spermatocytes exhibited oligosaccharides terminating with Galß1,3GalNAc and αGalNAc in the cytoplasm and nucleus, respectively. The spermatids contained highly mannosylated glycans terminating with GalNac, αGal, and αL-Fuc. The head of spermatozoa expressed a more complex glycosylation pattern characterized by the additional presence of oligosaccharides terminating with Neu5Acα2,3Galß1,4GlcNAc, Neu5AcGalß1,3GalNAc, Neu5AcGalNAcα1,3(LFucα1,2)Galß1,3/4GlcNAcß1, GalNAcα1,3(LFucα1,2)Galß1,3/4GlcNAcß1. The comparison with previous lectin histochemical studies carried out in other fish species reveals a specific glycosylation pattern of Senegalese sole testicular structures and spermatozoa head
- PublicationOpen AccessThe effects of Eicosapentaenoic acid on the endothelium of the carotid artery of rabbits on a high-cholesterol diet(Murcia : F. Hernández, 2010) Cayli, Sevil; Sati, Leyla; Seval-Celik, Yasemin; Altug Tuncer, M.; Yaymaci, Bengi; Berkman, Zafer; Altug, Tuncay; Demir, RamazanThe preventive and therapeutic effects ofEicosapentaenoic acid (EPA) on diet-inducedhyperlipidemia in rabbits have been investigated.Eighteen New Zealand rabbits were randomly dividedinto three groups of 6 subjects each; experimental group-I (EG-I) was administered a cholesterol rich diet,experimental group-II (EG-II) was treated with EPA(300 mg/kg/d) following a cholesterol-rich diet and thecontrol group (CG) had a standard diet. Blood sampleswere collected at day 0 and at the 4th and 12th weeks ofEG-II to obtain serum levels of total cholesterol (TC),high density lipid-cholesterol (HDL-C), low densitylipid-cholesterol (LDL-C) and triglyceride (TG). Fromeach group tissue samples were collected from thecarotid artery for immunohistochemistry and electronmicroscopy. Our results showed that EPA couldsignificantly lower (p<0.001) serum TC, LDL-C, HDL-C and TG levels with a reduction of 35%; 55%; 44% and51%, respectively. Scanning and transmission electronmicroscopy results revealed that endothelial damage wasmore prominent in EG-I when compared to EG-II. Theruptured endothelial lining and damaged cellular surfacewas increased in EG-I when compared to EG-II.Ultrastructural observations showed that after EPAtreatment, the degeneration and cellular surface damageon the endothelium were also decreased. These biochemical and ultrastructural results suggestthat EPA is a potential drug which significantly lowersthe serum lipid profile and partially repairs endothelialdysfunction due to hyperlipidemia