Histology and histopathology Vol.18, nº 1 (2003)

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Open Access
Exploring the connection between chronic renal fibrosis and bone morphogenic protein-7
(Murcia : F. Hernández, 2003) Kalluri, R.; Zeisberg, M.
Tubulointerstitial fibrosis is a hallmark feature of chronic renal injury. Specific therapies to control the progression of renal fibrosis towards endstage renal failure are still limited. Transforming growth factor-ß1 (TGF-ß1) has been identified as a major mediator of renal fibrosis. Recent reports have suggested that Bone Morphogenic Protein-7 (BMP-7), another member of the TGF-ß superfamily, accelerates repair of acute renal injury and ameliorates progression of chronic renal fibrosis in a variety of animal models. Interestingly, BMP-7, an endogenous molecule which is present in the normal kidney, vastly decreases its expression during renal injury. Although, the mechanism of BMP-7 action in the kidney is not yet fully understood, the idea of an endogenous molecule with reno-protective function is intriguing
Open Access
Dynamic assembly of tight junction-associated proteins ZO-1, ZO-2, ZO-3 and occludin during mouse tooth development
(Murcia : F. Hernández, 2003) Unda, F.; Pérez-Nanclares, G.; Le Morvan, V.; Hernández, C.; Vilaxa, A.; De-la-Fuente, M.; Gorry, P.
Tight junctions might play a role during tissue morphogenesis and cell differentiation. In order to address these questions, we have studied the distribution pattern of the tight junction-associated proteins ZO-1, ZO-2, ZO-3 and occludin in the developing mouse tooth as a model. A specific temporal and spatial distribution of tight junction-associated proteins during tooth development was observed. ZO-1 appeared discontinuously in the cell membrane of enamel organ and dental mesenchyme cells. However, endothelial cells of the dental mesenchyme capillaries displayed a continuous fluorescence at the cell membrane. Inner dental epithelium first showed an evident signal for ZO- 1 at the basal pole of the cells at bud/cap stage, but ZO-1 was accumulated at the basal and apical pole of preameloblast/ameloblasts at late bell stage. Surprisingly, in the incisor ZO-1 decreased as the inner dental epithelium differentiated, and was re-expressed in secretory and mature ameloblasts. On the contrary, ZO-2 was confined to continuous cell-cell contacts of the enamel organ in both molars and incisors. The lateral cell membrane of inner dental epithelial cells was specifically ZO-2 labeled. However, ZO-3 was expressed in oral epithelium whereas dental embryo tissues were negative. In addition, occludin was hardly detected in dental tissues at the early stage of tooth development, but was distributed continuously at the cell membrane of endothelial cells of ED19.5 dental mesenchyme. In incisors, occludin was detected at the cell membrane of the secretory pole of ameloblasts. The occurrence and relation during tooth development of tight junction proteins ZO-1, ZO-2 and occludin, but not ZO-3, suggests a combinatory assembly in tooth morphogenesis and cell differentiation.
Open Access
Expression of retinoblastoma gene product in respiratory epithelium and sinonasal neoplasms: relationship with p16 and cyclin D1 expression
(Murcia : F. Hernández, 2003) Schwerer, M.J.; Sailer, A.; Kraft, K.; Baczako, K.; Maier, H.
Transition from G1 to S phase of the cell cycle is mediated by interactions between the Retinoblastoma gene product (pRb), p16, and cyclin D1. To determine the expression of these proteins in the sinonasal mucosa immunohistochemistry was carried out on archived tissue sections from 46 patients (37 men, 9 women, age range 17 to 82 years, median 55 years). Nuclear immunostaining for these proteins was assessed and the expression rates (percentages of immunoreactive nuclei) in normal respiratory epithelium, inverted sinonasal papillomas, cylindrical (oncocytic) sinonasal papillomas, and squamous cell carcinomas were compared. Normal respiratory epithelium showed significantly higher pRb expression in surface cells compared to basal cells (p<0.05). In contrast, abundant pRb expression in surface and basal cells was detected in columnar differentiation in sinonasal papillomas and adjacent mucosa. Cuboidal and squamous metaplasia in inverted papillomas showed significantly reduced pRb expression in surface cells compared to columnar epithelium in inverted papillomas (p<0.05, respectively). Expression of p16 was detected in all epithelial cell layers of normal respiratory epithelium, sinonasal papillomas, and adjacent mucosa. Cuboidal and squamous metaplasia in inverted papillomas showed increased p16 expression in surface cells compared to columnar epithelium in inverted papillomas (p<0.05 between squamous metaplasia and columnar epithelium). Sinonasal squamous cell carcinomas showed the coexpression of pRb and p16. Expression rates of cyclin D1 higher than 10% were detected only in invasive carcinomas but not in carcinoma in situ, sinonasal papillomas or respiratory epithelium. Conclusively, pRb expression accompanies terminal differentiation in columnar surface cells. Expression of pRb in proliferating basal cells is present in sinonasal papillomas and adjacent mucosa but not in normal respiratory epithelium. Cuboidal and squamous metaplasia in inverted papillomas involves downregulation of pRb expression along with increased p16 expression in surface cells. Sinonasal squamous cell carcinomas coexpress pRb and p16. Overexpression of cyclin D1 in sinonasal lesions is confined to invasive squamous cell carcinomas.
Open Access
Diagnostic differentiation of essential thrombocythaemia from thrombocythaemias associated with chronic idiopathic myelofibrosis by discriminate analysis of bone marrow features - a clinicopathological study on 272 patients
(Murcia : F. Hernández, 2003) Thiele, J.; Kvasnicka, H.M.
Until now diagnosis of essential thrombocythaemia (ET) is generally performed by following the criteria of the Polycythaemia Vera Study Group (PVSG) that only marginally regards morphological features. Bone marrow biopsies were studied from 272 patients with ET in strict accordance with the PVSG guidelines and also from 35 control patients with reactive thrombocytosis. To define morphological features of distinctive impact more accurately, we performed a stepwise discriminant analysis of 16 morphological parameters based on histochemical staining reactions and semiquantitative grading of standardized features. A clear-cut separation into three distinctive histological patterns was accomplished that showed in more than 96% a correct predicted classification. Variables of significant impact included fibre content, quantity and cytological abnormalities of megakaryopoiesis like bulbous (cloudlike) nuclei, degree of nuclear lobulation and presence of giant forms. These changes were not detectable in the control group. The different constellations of histopathological features could be assigned to true ET (98 patients) and false ET, i.e. 136 patients with prefibrotic and 38 patients with early fibrotic chronic idiopathic myelofibrosis (IMF) accompanied by thrombocythaemia. A re-evaluation of clinical findings was in keeping with this classification into three categories that exerted significant differences to develop myelofibrosis during observation time and also different survival patterns. Contrasting IMF true ET is characterized by a pronounced proliferation of the megakaryocyte lineage showing large to giant cells without maturation defects and no relevant increase in reticulin fibres. Discrimination between these entities is warranted, because of a significant difference in presenting haematological data, follow-up and life expectancy.
Open Access
Scanning electron microscopic examinations on retarded bone defect healing in spontaneously diabetic BB/O(ttawa)K(arlsburg) rats
(Murcia : F. Hernández, 2003) Follak, N.; Klöting, I.; Ganzer, D.; Merk, H.
To date, no detailed knowledge from animal experiments is available on the kind and extent of osseous and mineral metabolic disorders in genetically determined, insulin-dependent Type I diabetes. The purpose of this study was to examine the influence of the diabetic metabolic state in spontaneously diabetic BB/O(ttawa)K(arlsburg) rats on bone defect healing. Eighty spontaneously-diabetic BB/OK rats with a blood-glucose value of 391±106 mg% (mean ± SD) at the time of manifestation were used in the study. Based on blood-glucose values at the time of surgery (mg%), postoperative blood-glucose course (mg%) and postoperative insulin requirements (IU/kg), the animals were divided into groups with well-compensated (n=40, 170±101 mg%; 221±120 mg%; 2.1±1 IU/kg) or poorly compensated (n=40; 371±158 mg%; 357±83 mg%; 5.2±1.4 IU/kg) metabolic state. Forty LEW.1A rats served as the normoglycemic controls (95±18 mg%). Using a 1-mm-diameter Kirschner wire, a hole of femoral bone ca. 1 cm proximal to the knee joint space was centrally drilled. Ten animals from each group were killed on postoperative days 7, 14, 24, and 42, and specimens were taken for analysis. Using SEM to measure regions of new bone semiautomatically and quantitatively, also determining the number, area, and circumference of regions not yet filled with new bone. Up to postoperative day 14, very significant differences (p<0.0001) for all investigated characteristics were found between the spontaneously-diabetic BB/OK rats and the control animals – in favor of the controls – and up to postoperative day 24 within the group of spontaneously-diabetic BB/OK rats, where the wellcompensated animals had significantly better results in terms of number and area of regions of bone not yet filled with new bone formations. Forty-two days postoperatively, SEM observations showed no differences between examination groups. The process of bone defect healing in spontaneously-diabetic rats was disturbed only in the early phase and exhibited retardation in its progression. After 42 days, bone defect healing was complete, regardless of the diabetic metabolic state; no differences were detected with the SEM between examination groups at this time point.
Open Access
Expression of c-fos and c-jun protooncogenes in the uteri of immature mice neonatally exposed to diethylstilbestrol
(Murcia : F. Hernández, 2003) Yamashita, S.; Takayanagi, A.; Shimizu, N.
We studied the cell-type-specific and temporal expression of c-fos and c-jun protooncogenes after 17ß-estradiol (E2) stimulation in the uteri of immature 3-week-old mice neonatally exposed to diethylstilbestrol (DES), DES-mice, and the ontogenic expression of these genes in the uteri of DES-mice using immunohistochemistry and in situ hybridization. A single E2 injection induced the transient and rapid expression of c-fos mRNA and c-Fos protein in the endometrial epithelium and endothelial cells of the blood vessels in both 3-week-old vehicle-treated controls and DES-mice; a peak of mRNA expression was 2 hours after E2 injection and that of protein expression was 2 to 3 hours after the injection. The expression of c-fos mRNA and protein after E2 stimulation was lower in the DES-mice than in the control animals. There were no significant differences in the c-jun expression patterns in both experimental groups before and after the E2 injection. The E2 injection transiently down-regulated the c-jun expression in the epithelium and up-regulated it in the stroma and myometrium. The uterine epithelium of DES-mice showed much stronger c-Jun immunostaining on days 4 and 10, compared with those of controls. Neonatal DES treatment reduced c-Jun immuoreactivity in the uterine epithelium on days 4 and 10, and increased the reaction in the stroma on day 4. These results suggested that the neonatal DES treatment induces permanent changes in the c-fos expression pattern independent of the postpuberal secretion of ovarian steroids. The changes in the expression of c-fos and c-jun protooncogenes, particularly during postnatal development, are likely to play important roles in the production of uterine abnormalities in the DES-mice.
Open Access
Case report, esophageal collision tumor (oat cell carcinoma and adenocarcinoma) in Barrett´s esophagus: immunohistochemical, electron microscopy and LOH analysis
(Murcia : F. Hernández, 2003) González, L.M.; Sanz Esponera, J.; Saez, C.; Alvarez, T.; Sierra, E.; Sanz Ortega, J.
We report a case of an esophageal collision tumor composed of adenocarcinoma and oat cell carcinoma. Both tumors appeared to arise from dysplastic Barrett's mucosae in a 75-year-old man. Immunohistochemical stains and electron microscopy demonstrated a separate identity for each of the tumors in collision. Molecular analysis of microsatellite regions was performed in different microdissected areas. Identical loss of heterozygosity (LOH) at 9p21 and 17p13 was determined in the three different microdissected areas of the adenocarcinoma component. LOH was not determined in any area of the oat cell carcinoma. This is the first study that analyzes the allele status of an esophageal collision tumor. Our findings suggest a biclonal origin for both components of the collision tumor.
Open Access
A comparison between double and triple therapies of octreotide, galanin and serotonin on a rat colon carcinoma
(Murcia : F. Hernández, 2003) Sitohy, B.; El-Salhy, M.
Sixty female nude mice (C578L/6jBom-nu) were injected with 100µl cell suspension containing 2x106 viable cells of an N-methyl-N-nitroguanidineinduced rat colonic adenocarcinoma. After seven days the animals were divided into five groups. The first group received only saline and served as a control group. The second group received a triple therapy of octreotide, galanin and serotonin (20 µg/kg). The last three groups received double therapies of octreotide/galanin, octreotide/serotonin or galanin/serotonin (20 µg/kg). They were treated twice a day for five days. Tumour volume and weight, relative volume density of tumourfeeding blood vessels and of tumour necrotic tissue, as well as apoptotic and proliferation indices were determined. Animal weight, food consumption, faeces weight and its water content were recorded before and after treatment. Tumour volume was significantly reduced only in the group that received the triple therapy. The volume density of the tumour-feeding blood vessels was significantly reduced in the treated groups with the exception of the group that received octreotide and serotonin. Increased relative volume density of tumour necrotic tissue occurred only in the group treated with triple therapy. Apoptotic indices were significantly increased in all treated groups. No statistical difference was found between treated animals and controls regarding proliferation indices, food consumption, faeces weight and water content or animal weight. In conclusion, double therapy using two of the gastrointestinal bioactive substances, octreotide, galanin and serotonin, has certain effects on colon cancer cells. To cause a considerable tumour necrosis, triple therapy seems to be required. Both double and triple therapy seem to lack obvious side-effects.
Open Access
Modeling human breast cancer metastasis in mice: maspin as a paradigm
(Murcia : F. Hernández, 2003) Shi, H.Y.; Zhang, W.; Liang, R.; Kittrell, F.; Templeton, N.S.; Medina, D.; Zhang, M.
Breast cancer is the most common cancer detected in women, accounting for nearly one out of every three cancers diagnosed in the United States. Most cancer patients do not die from the primary tumor but die due to metastasis. Therefore, the study of metastasis is of most importance both to the clinician and patient. In the past, animal models have been used in breast cancer research and mammary gland biology. Our group has also established several animal models to address the function of a novel tumor suppressor gene maspin in breast tumor progression. Maspin was initially isolated from normal mammary epithelial cells. Its expression was down regulated in breast tumors. To test the protective role of maspin overexpression in mammary tumor progression, we crossed maspin overexpression transgenic mice (WAP-maspin) with a strain of oncogenic WAP-SV40 T antigen mice. The bitransgenic mice had reduced tumor growth rate and metastasis. Maspin overexpression increased the rate of apoptosis of both preneoplastic and carcinomatous mammary epithelial cells. Maspin reduced tumor growth through a combination of reduced angiogenesis and increased apoptosis. In a separate animal experiment, maspin overexpressing mammary tumor cells (TM40D) were implanted into the fat pad of syngeneic mice. TM40D tumor cells were very invasive and metastatic. However, both primary tumor growth and metastasis were significantly blocked in TM40D cells that overexpress maspin as a consequence of plasmid or retrovirus infection. These evidences demonstrate that maspin function to inhibit primary tumor growth as well as invasion and metastasis. Elucidating the molecular mechanism of maspin action will shed light on our understanding of breast cancer invasion and metastasis.
Open Access
Murine embryonic stem cell in vitro differentiation: applications to the study of vascular development
(Murcia : F. Hernández, 2003) Feraud, O.; Vittet, D.
The present review summarizes knowledge accumulated during the last decade concerning in vitro endothelial differentiation from embryonic stem (ES) cells. There is now growing evidence that ES cells may provide a powerful model system to determine the cellular and molecular mechanisms of vascular development. ES cells differentiate into the endothelial lineage by successive maturation steps recapitulating in vivo events observed in the embryo. Further maturation of ES-derived embryoid bodies either in three dimensional gels or in confrontation cultures with tumor spheroids can also provide a model of physiological or tumoral angiogenesis. The data obtained from experimental in vitro differentiation of genetically modified mouse ES cells highlight the potential and the complementarity of this model system to in vivo gene knock out studies. We also consider and discuss some of the potential applications of ES cell technology in vascular biology for future directions in basic research and medicine, by manipulation of differentiation and the generation of cell populations for analysis and transplantation for therapeutic use.
Open Access
Styrene hepatotoxicity in rats treated by inhalation or intraperitoneally: a structural investigation
(Murcia : F. Hernández, 2003) De Piceis Polver, P.; Fenoglio, C.; Nano, R.; Coccini, T.; Bertone, V.; Vaccarone, R.; Gerzeli, G.
The purpose of this study was to investigate the toxicity of styrene in the liver of adult rats treated either by inhalation of styrene vapour (300 ppm, 6 h/d, 5 d/wk, for 2 wk) or intraperitoneally with different styrene doses (4, 40, 400 mg/Kg) for 3 consecutive days. Using a light microscope, some alterations of liver parenchyma and sinusoid dilation were noticed, more marked in the group treated with the intraperitoneal administration of the chemical. Using an electron microscope, some additional changes were observed (once again, more marked in the latter group of rats): a) an increase in the content of lipids inside hepatocytes, and b) the rise of intracytoplasmic, intercellular and perisinusoidal collagen fibres. Therefore, cell damage and functional disturbance of sinusoids due to perisinusoidal fibrosis are apparent in the liver of both groups of rats exposed to styrene treatment, but these changes are definitely more significant in those subjected to intraperitoneal administration.
Open Access
Metabotropic glutamate receptors promote neuronal and vascular plasticity through novel intracellular pathways
(Murcia : F. Hernández, 2003) Chong, Z.Z.; Kang, J.Q.; Maiese, K.
During the initial development and maturation of an individual, the metabotropic glutamate receptor (mGluR) system becomes a necessary component for the critical integration of cellular function and plasticity. In addition to the maintenance of cellular physiology, the mGluR system plays a critical role during acute and chronic degenerative disorders of the central nervous system. By coupling to guanosinenucleotide- binding proteins (G-proteins), the mGluR system employs a broad range of signal transduction systems to regulate cell survival and injury. More commonly, it is the activation of specific mGluR subtypes that can prevent programmed cell death (PCD) consisting of two distinct pathways of genomic DNA degradation and membrane phosphatidylserine (PS) residue exposure. To offer this cellular protection, mGluRs modulate a series of down-stream cellular pathways that include protein kinases, mitochondrial membrane potential, cysteine proteases, intracellular pH, endonucleases, and mitogen activated protein kinases. Prevention of cellular injury by the mGluR system is directly applicable to clinical disability, since immediate and delayed injury paradigms demonstrate the ability of this system to reverse PCD in both neuronal and vascular cell populations. Further understanding of the intricate pathways that determine the protective nature of the mGluR system will provide new therapeutic avenues for the treatment of neurodegenerative disorders.
Open Access
Expression and induction of anaphylatoxin C5a receptors in the rat liver
(Murcia : F. Hernández, 2003) Schlaf, G.; Schmitz, M.; Rothermel, E.; Jungermann, K.; Schieferdecker, H.L.; Götze, O.
The C5a-anaphylatoxin which is generated by limited proteolysis upon activation of the fifth component of complement may be induced by the classical, the alternative or the lectin pathway. C5a has been shown, under normal conditions, to induce the release of prostanoids from Kupffer cells (KC) and hepatic stellate cells (HSC) and thereby indirectly to increase glucose output from hepatocytes (HC). A direct action of C5a on HC would require the expression of the specific C5a receptor (C5aR). In studies using quantitative RT-PCR it was shown that non-stimulated HC lack C5aR, in contrast to KC, HSC and sinusoidal endothelial cells (SEC) all of which contained mRNA for the C5aR in decreasing amounts. FACS analyses, immunohisto- and immunocytochemistry as well as functional analyses confirmed the results of the RT-PCR assays. Under inflammatory situations the C5aR was found to be upregulated in various organs and tissues which included the liver. Interleukin-6 (IL-6) as a main inflammatory mediator in the liver induced a de novo expression of functional C5aR in HC in-vitro and invivo. In contrast, LPS failed to induce C5aR directly in cultured HC in-vitro but induced C5aR in HC in vivo and in co-cultures of HC and KC which release IL-6 upon stimulation with LPS. So far, the only known effector function of C5a on HSC was the induction of prostanoid release. In an approach to reveal new functions of C5aR in HSC, the cells responsible for liver fibrosis, it could be shown that C5a upregulated fibronectin-specific mRNA five-fold whereas entactin, collagen IV and the structure protein smooth muscle actin were not affected. In addition, C5a did not upregulate specific mRNA for the profibrotic cytokine TGF-ß1 in either isolated KC or HSC. Thus, C5a alone appears to have only a limited role in the induction of liver fibrosis.
Open Access
PTTG and cancer
(Murcia : F. Hernández, 2003) Hamid, T.; Kakar, S.S.
Pituitary tumor transforming gene (pttg) is a recently isolated oncogene that is expressed in most of the tumors. Overexpression of pttg results in an increase in cell proliferation, induces cell transformation in vitro, and promotes tumor formation in nude mice. The gene encodes a protein of 202 amino acids with no significant homology with other known proteins. The protein is a multi domain consisting of a transactivation domain, domain required for ubiquitin-mediated proteolysis and a DNA binding domain. pttg protein is bestowed with a multitude of functions and seems to be involved in most of the important mechanisms of cell proliferation, differentiation and signaling. Given the number of processes that are involved in the manifestation of cancer, it thus becomes mandatory to study the role of this potent oncogene in relation to the processes of cell survival, death and functioning.
Open Access
Angiogenesis after sintered bone implantation in rat parietal bone
(Murcia : F. Hernández, 2003) Ohtsubo, S.; Matsuda, Mikio; Takekawa, M.
We studied the effect of bone substitutes on revascularization and the restart of blood supply after sintered bone implantation in comparison with synthetic hydroxyapatite implantation and fresh autogenous bone transplantation (control) in rat parietal bones. Methods for the study included the microvascular corrosion cast method and immunohistochemical techniques were also used. The revascularization of the control group was the same as that for usual wound healing in the observations of the microvascular corrosion casts. The sintered bone implantation group was quite similar to that of the control group. In the synthetic hydroxyapatite group, immature newly-formed blood vessels existed even on the 21st day after implantation and the physiological process of angiogenesis was interrupted. Immunohistochemically, vascular endothelial growth factor (VEGF), which activates angiogenesis, appeared at the early stages of both the control group and the sintered bone implantation group. VEGF reduced parallel with the appearance of the transforming growth factor factor-beta-1 (TGF-beta-1), which obstructs angiogenesis, and the angiogenesis passed gradually into the mature stage. In the hydroxyapatite implantation group, TGF-beta-1 appeared at the early stage of the implants. The appearance of VEGF lagged and it existed around the pores of hydroxyapatite even on the 21st day of the implantation. Proliferation and wandering of endothelial cells continued without any maturing of the vessels. These findings suggest that the structure and the components of the implant material affect angiogenesis after implantation as well as new bone formation.
Open Access
A COX-2 inhibitor, nimesulide, inhibits chemically-induced rat tongue carcinogenesis through suppression of cell proliferation activity and COX-2 and iNOS expression
(Murcia : F. Hernández, 2003) Yoshida, K.; Tanaka, T.; Kohno, H.; Sakata, K.; Kawamori, T.; Mori, H.; Wakabayashi, K.
The modifying effects of a cyclooxygenase (cox)-2 selective inhibitor nimesulide on tongue carcinogenesis were investigated in male F344 rats initiated with 4-nitroquinoline-1-oxide (4-NQO). The cell proliferation activity measured by proliferating cell nuclear antigen (PCNA)-positive index and apoptotic index, and the immunohistochemical expression of COX-2, and inducible nitric oxide synthase (iNOS) in the tongue mucosa or neoplasms were also examined for mechanistic analysis of modifying effects of nimesulide on tongue carcinogenesis. All animals except those treated with nimesulide alone and untreated rats were given 20 ppm 4-NQO in drinking water for 8 weeks to induce tongue neoplasms. Starting 1 week after the cessation of 4-NQO exposure, rats given 4-NQO were fed the experimental diets containing nimesulide (100 and 400 ppm) for 22 weeks. At week 32, the incidence of tongue squamous cell carcinoma was significantly reduced by feeding of the diet containing 400 ppm nimesulide. Feeding of nimesulide significantly decreased polyamine content and PCNA-labeling index in tongue carcinoma. Apoptotic index in tongue carcinoma was increased by feeding of nimesulide. In addition, nimesulide feeding reduced COX-2 and iNOS expression in the tongue dysplasia and neoplasms. These results suggest that 400 ppm nimesulide in diet, when given during the promotion phase, exerts chemopreventive ability against 4-NQO-induced tongue tumorigenesis through inhibition of cell proliferation activity in conjunction with modification of COX-2 and iNOS expression of the target lesions.
Open Access
Molecular pathogenesis of urothelial bladder cancer
(Murcia : F. Hernández, 2003) Theodorescu, D.
Carcinoma of the urinary bladder is the second most common urologic malignancy. In addition, these tumors are one of the best understood genitourinary neoplasms with a well defined etiology, natural history, tumor biology, treatment options and outcome. This level of understanding arises as a consequence of multiple factors and represents a convergence of knowledge from diverse scientific disciplines. Insight provided by these disciplines, coupled with unique features of this neoplasm which make it assessable for detection, monitoring and treatment, combine to make this disease a model system for modern oncology. The intent of this review is to provide the reader an overview of our current understanding of this tumor from the standpoint of its molecular biology as related to tumor development and progression.
Open Access
Molecular biology of glioma tumorigenesis
(Murcia : F. Hernández, 2003) Ware, M.L.; Berger, M.S.; Binder, D.K.
Gliomas are the most common intracranial malignant tumors in humans, and high-grade gliomas in particular pose a unique challenge due to their propensity for proliferation and tissue invasion. Our understanding of glioma oncogenesis, proliferation, and invasion has been greatly advanced in the past 10 years as researchers have gained a better understanding of the molecular biology of these tumors. This article highlights glioma histopathology, as well as cytogenetic and molecular alterations associated with the pathogenesis of human gliomas. It is hoped that better understanding of the molecular pathogenesis of gliomas will improve tumor classification as well as lead to novel targets for therapy and prognostic markers.
Open Access
Role of chromatin disruption and histone acetylation in thyroid hormone receptor action: implications in the regulation of HIV-1 LTR
(Murcia : F. Hernández, 2003) Hsia, S.C.V.; Tomita, A.; Obata, Kazuya; Paul, B.; Buchholz, D.; Shi, Y.B.
Thyroid hormone (TH) affects a wide variety of biological processes, from development to physiological function of different cells and organs. Alterations in plasma TH concentrations lead to developmental abnormalities and pathological consequences. Earlier studies have observed that plasma TH levels vary in AIDS patients such that low levels of TH correlate with survival rate. Furthermore, studies on the regulation of the human immunodeficiency virus type 1 (HIV-1) have shown that TH receptor (TR) is capable of binding to two regions within the long terminal repeat (LTR), which controls the transcription of HIV-1 genome. The frog oocyte is an in vivo system that allows microinjected DNA to be chromatinized in a process mimicking the process that occurs in somatic cells. Studies in the frog oocyte have provided in vivo evidence on the role of chromatin remodeling in transcriptional regulation by TR and have shown that TR utilizes similar mechanisms in the regulation of the HIV- 1 LTR. That is, TR binds to LTR in chromatin in vivo and represses the LTR in the absence of TH by recruiting corepressor complexes containing histone deacetylases, and upon TH binding, TR causes chromatin remodeling and LTR activation.
Open Access
Morphological hysteresis of the small airways
(Murcia : F. Hernández, 2003) Escolar Castellón, J.de D.; Escolar, M.A.; Guzmán, J.; Roqués, M.
The resistance to airflow that develops in most obstructive processes takes place in the small airways. The aim of the present paper is to describe bronchial hysteresis morphometrically in a respiratory cycle model. As a working hypothesis, it is proposed that the changes that take place in the respiratory tract during the respiratory cycle are related to the bronchial size. Specimen rat lungs were organized into five groups: In the first group, the lungs were filled with a liquid fixative to 25 cm of H2O transpulmonary pressure. The following four groups were inflated with air and fixed through the pulmonary artery. Groups 2 and 3 were fixed at 10 and 20 cm transpulmonary pressure in inflation. The last two groups were fixed in deflation and, for this purpose, the transpulmonary pressure was increased to 27 cm and decreased to 20 and 10 cm, respectively. The lungs were processed for morphometrical study and the following variables were quantified: pulmonary volume, internal area, internal perimeter, wall area, internal area radius and bronchial wall radius. The diameter of the airways studied varied between 84.06 µm and 526.4 µm. The results were classified into three subgroups consisting of small, medium-sized and large bronchi. With a single exception - the internal area in the medium-sized bronchi inflated to 20 cm - all the results obtained in deflation were higher than those obtained in inflation. The internal area increased or decreased significantly upon raising or lowering the transpulmonary pressure respectively, in the small and medium-sized bronchi. The wall area in the large bronchi showed significant differences between inflation and deflation at 10 and 20 cm transpulmonary pressure. The wall area was modified significantly in the lungs fixed at 20 cm in the small bronchi and at 10 cm in medium-sized bronchi. The bronchial wall radius was significantly greater in the large bronchi and smaller in the small bronchi. The lumen of the medium-sized and small bronchi increases in inspiration and decreases in expiration. The wall thickness displayed differences between inflation and deflation. The most marked hysteresis was presented by the bronchial wall in the large bronchi. Our results suggest that the behavior of the bronchi varies according to their size