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1.
Nuklearmedizin ; 46(1): 43-8, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17299654

RESUMEN

AIM: Comparison of anatomical accuracy of software-based interactive (IRR) and automated rigid registration (ARR) of separately acquired CT and FDG-PET data sets. PATIENTS, METHODS: Independently acquired PET and helical CT data from 22 tumour patients were registered manually using the Syngo advanced Fusion VC20H tool. IRR was performed separately for the thorax and the abdomen using physiological FDG uptake in several organs as a reference. In addition, ARR was performed with the commercially available software tool Mirada 7D on all of the patients. For both methods, the distances between the representation of 53 malignant lesions on PET and CT were measured in X-, Y-, and Z-direction with reference to a common coordinate system (X-, Y-, Z-distances). RESULTS: The percentage of lesions misregistered by less than 1.5 cm was in X-direction 91% for IRR and 89% for ARR; in Y-direction 85% and 68%; in Z-direction 72% and 51%, respectively. The average X-, Y- and Z-distances for IRR ranged from 0.58 +/- 0.55 cm (X-direction) to 1.17 +/- 1.66 cm (Z-direction). For ARR, the average X-, Y- and Z-distances varied between 0.66 +/- 0.61 cm (X-direction) and 1.81 +/- 1.37 cm (Z-direction). Mixed effects analysis of the absolute X-, Y- and Z-distances revealed a significantly better alignment for IRR compared to ARR in Z-direction (p < 0.01). Lesion size and localization either in thorax or abdomen had no significant influence on the accuracy of registration. CONCLUSION: For the majority of malignant lesions, manual image registration with the possibility to separately align different body segments was more accurate than the automated approach. Current software for ARR does not reach the anatomical accuracy reported for PET/CT hybrid scanners.


Asunto(s)
Neoplasias/diagnóstico por imagen , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Anciano , Automatización , Femenino , Fluorodesoxiglucosa F18 , Humanos , Linfoma/diagnóstico por imagen , Linfoma/patología , Masculino , Melanoma/diagnóstico por imagen , Melanoma/patología , Persona de Mediana Edad , Neoplasias/patología , Radiofármacos , Reproducibilidad de los Resultados , Resultado del Tratamiento
2.
Am J Pathol ; 156(6): 1841-8, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10854207

RESUMEN

Catechol-O-methyltransferase (COMT) plays both a regulatory and protective role in catechol homeostasis. It contributes to the regulation of tissue levels of catecholamines and catecholestrogens (CEs) and, by blocking oxidative metabolism of catechols, prevents endogenous and exogenous catechols from becoming a source of potentially mutagenic electrophiles. Evidence implicating CEs in carcinogenesis, in particular in the hamster kidney model of estrogen-induced cancer, has focused attention on the protective role of COMT in estrogen target tissues. We have previously reported that treating hamsters with estrogens causes translocation of COMT to nuclei of epithelial cells in the renal cortex, the site of CE biosynthesis and where the cancers arise. This finding suggested that nuclear COMT may be a marker of a threat to the genome by catechols, including CEs. It is postulated that CEs play a role in the genesis of breast cancer by contributing to a state of chronic oxidative stress that is presumed to underlie the high incidence of this disease in the United States. Therefore, here we used immunocytochemistry to re-examine human breast parenchyma for nuclear COMT. In addition to confirming previous reports of cytoplasmic COMT in mammary epithelial cells, we identified nuclear COMT in foci of mammary epithelial cells in histologically normal breast tissue of virtually all control (macromastia) and cancer patients and in breast cancer cells. There was no correlation between tissue histology and the numbers of cells with nuclear COMT, the size of foci containing such cells, or intensity of nuclear COMT immunostaining. The focal nature of the phenomenon suggests that nuclear COMT does not serve a housekeeping function but that it reflects a protective response to an increased local catechol load, presumably of CEs and, as such, that it may be a characteristic of the population of women studied who share the same major risk factor for developing breast cancer, that of living in the industrialized West.


Asunto(s)
Neoplasias de la Mama/enzimología , Mama/enzimología , Catecol O-Metiltransferasa/metabolismo , Núcleo Celular/enzimología , Adolescente , Adulto , Mama/citología , Neoplasias de la Mama/patología , Células Epiteliales/enzimología , Femenino , Humanos , Persona de Mediana Edad , Distribución Tisular
3.
Carcinogenesis ; 19(7): 1307-12, 1998 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9683193

RESUMEN

Catecholestrogens are postulated to contribute to carcinogenesis by causing DNA damage mediated by reactive oxygen species generated during redox cycling between catechol and quinone estrogens, and by quinone estrogens that can form depurinating adducts. The above hypothesis is based principally on studies of the cancers that develop in renal cortex of hamsters treated with primary estrogens: Hamster kidney can catalyze 2- and 4-hydroxylation of estrogens and support their redox cycling, and the kidneys of estradiol-treated hamsters show evidence of oxidative cellular and DNA damage. Here we used immunocytochemisty to test the postulate that catechol-O-methyltransferase (COMT), the enzyme that can prevent oxidation of catecholestrogens to their quinone derivatives, would be induced in renal cortex of hamsters treated with estradiol or ethinyl estradiol. In kidneys of control hamsters, COMT was localized in cytoplasm of epithelial cells of proximal convoluted tubules, predominantly in the juxtamedullary region where the estrogen-induced cancers arise. After 2- or 4-weeks of treatment with either estrogen, COMT was seen in epithelial cells of proximal convoluted tubules throughout the cortex, and many cells also showed intense nuclear COMT immunoreactivity. Estradiol-induced renal cancers were negative for COMT, but were surrounded by tubules with intense cytoplasmic and nuclear immunostaining. The nucleus-associated COMT was shown by immunoblot analysis to be the soluble form of the enzyme. Using reverse transcription-polymerase chain reaction amplification, hamster kidney COMT was shown to lack the putative nuclear localization signal sequence present in human COMT. A second phase II enzyme, CuZn-superoxide dismutase (CuZnSOD), was shown by immunocytochemistry to remain extranuclear in proximal convoluted tubules of estrogen-treated hamsters, which indicates entry of COMT into the nucleus to be selective. The findings are consistent with the catechol/quinone estrogen hypothesis of estrogen-induced cancer, while the translocation of the enzyme to the nucleus following estrogen treatment suggests a response to a threat to the genome by electrophilic products of catechols.


Asunto(s)
Catecol O-Metiltransferasa/biosíntesis , Congéneres del Estradiol/toxicidad , Estradiol/toxicidad , Etinilestradiol/toxicidad , Neoplasias Renales/inducido químicamente , Neoplasias Renales/enzimología , Riñón/efectos de los fármacos , Riñón/enzimología , Proteínas Nucleares/biosíntesis , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Cricetinae , Inducción Enzimática/efectos de los fármacos , Humanos , Immunoblotting , Inmunohistoquímica , Corteza Renal/efectos de los fármacos , Corteza Renal/enzimología , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/enzimología , Masculino , Mesocricetus , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Sensibilidad y Especificidad , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , Fracciones Subcelulares/enzimología , Superóxido Dismutasa/metabolismo , Transcripción Genética
4.
Am J Physiol ; 272(1 Pt 2): R275-88, 1997 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9039019

RESUMEN

Glucose utilization and Fos expression were used to compare responses of cerebral structures involved in osmoregulation in virgin and lactating rats given 0.15, 0.85, or 1.5 M NaCl subcutaneously. In virgin animals, glucose utilization increased (P < 0.05) in the supraoptic nuclei (SON), paraventricular nuclei (PVN), and neural lobe (NL) proportionally to the osmotic stimulus (0.15 M NaCl < 0.85 M NaCl < 1.5 M NaCl), whereas metabolism in the median preoptic nucleus (MPO) and median eminence (ME) increased only after 1.5 M NaCl. In lactating rats, enhanced utilization of glucose in response to osmotic stimulation was absent in the PVN (0.85 M NaCl), MPO, and ME or significantly (P < 0.01) reduced (SON, PVN, NL) compared with virgin animals. Glucose utilization in each structure correlated linearly with plasma osmolality but with a lower slope (P < 0.05) in lactating animals. Magnocellular neurons expressing Fos in the SON increased linearly with plasma osmolality and were more numerous (P < 0.05) in control lactating animals but increased less (P < 0.05) than in virgin rats after 0.85 M NaCl. The attenuated magnocellular response during lactation results from reduced afferent activation from osmosensitive forebrain sites.


Asunto(s)
Encéfalo/metabolismo , Encéfalo/fisiología , Lactancia/fisiología , Sistemas Neurosecretores/fisiología , Equilibrio Hidroelectrolítico , Animales , Encéfalo/citología , Ácidos Grasos/metabolismo , Femenino , Glucosa/metabolismo , Neuronas/metabolismo , Embarazo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Sprague-Dawley , Solución Salina Hipertónica/farmacología , Núcleo Supraóptico/citología , Núcleo Supraóptico/metabolismo
5.
Endocrinology ; 137(7): 3061-8, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8770932

RESUMEN

The expression of aromatase by breast cancer cells and the role of locally produced estrogen in the stimulation of tumor growth has been controversial. The present study was performed to determine the site of aromatization in human breast cancers, using both immunocytochemistry and in situ hybridization. The functional significance of locally produced estrogens on growth of the tumor was addressed by measuring aromatase activity and a marker of proliferation (PCNA score). In addition, histocultures of some tumors were carried out to investigate whether testosterone aromatization could stimulate tumor proliferation. Of the 19 tumors investigated, 10 (52.6%) showed significant immunoreactivity to antiaromatase antibody in the cytoplasm of tumor epithelial cells and in surrounding stromal cells. The presence of aromatase mRNA detected by ISH was also located in tumor epithelial cells and stromal cell, and the pattern of expression was the same as with immunocytochemistry. In the ten tumors that showed immunoreaction to aromatase, the average aromatase activity measured in cryosections was 286.5 +/- 18.6 (SE) fmol estrogen/mg protein.h, whereas in nine tumors with weak aromatase immunoreaction, the enzyme activity was 154.7 +/- 19.3 (SE) fmol estrogen/mg protein-h (P < 0.05). The mean PCNA score was 33.8 +/- 5.1 (SE)% in strongly stained tumors and 20.8 +/- 2.0 (SE)% in weakly stained tumors (P < 0.05). Aromatase activity level and PCNA score were significantly correlated. In histoculture of four tumors, estradiol increased the incorporation of [3H]-thymidine into DNA. In two of these tumors, aromatase activity was high and [3H]-thymidine incorporation into DNA was also stimulated by testosterone. In the other two tumors that had low aromatase activity, no such stimulation occurred with testosterone. The results indicate that aromatase is expressed mainly in tumor epithelial cells and that sufficient amounts of estrogen are synthesized by the tumor to produce a proliferative response. It is concluded that estrogen synthesis by cancer cells could play a important role in promoting growth in a significant proportion of breast tumors.


Asunto(s)
Aromatasa/biosíntesis , Neoplasias de la Mama/enzimología , Regulación Enzimológica de la Expresión Génica , Biosíntesis de Proteínas , ARN Mensajero/biosíntesis , Transcripción Genética , Secuencia de Bases , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/enzimología , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/enzimología , Carcinoma Lobular/patología , Cartilla de ADN , Sondas de ADN , Epitelio/enzimología , Epitelio/patología , Estradiol/biosíntesis , Estrona/biosíntesis , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Posmenopausia , Premenopausia , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis
6.
Cell Growth Differ ; 7(5): 635-46, 1996 May.
Artículo en Inglés | MEDLINE | ID: mdl-8732673

RESUMEN

Rats were treated with low doses of the hepatocarcinogens dimethylnitrosamine or thioacetamide, and livers were examined 48 h later. These treatments are known to produce altered RNA compartmentation, wherein a class of repetitive RNA sequences normally restricted to the nucleus appears in the cytoplasm. Reverse transcription-PCR amplifications demonstrated that the sequences showing altered compartmentation consisted largely of a subfamily of the rodent B2 sequence family, the counterpart of human Alu sequences involved in retrotransposition. Northern blot analyses showed that these B2 sequences were found in cytoplasmic RNA as 170- to 360-nucleotide "sense" transcripts, and competition hybridization experiments established that B2 sequences represented most (if not all) of the sequences showing altered compartmentation. The major increase in B2 transcriptions in cytoplasmic RNA was not associated with any change in B2 transcription by RNA polymerase III. In situ hybridizations showed that the altered compartmentation of B2 sequences occurred in well-delineated foci within the rat liver; these foci consisted of a central region containing a prominent infiltrate of macrophages admixed with small hepatocytes and a peripheral region of histologically normal hepatocytes that showed evidence of oxidative damage. Altered compartmentation of B2 sequences may represent an important focal initiatory change in a subset of hepatocytes, whereas subsequent retrotranspositional events (associated with Alu-like sequences) could predispose initiated cell foci to alterations in promotion/progression phases.


Asunto(s)
Carcinoma Hepatocelular/genética , Compartimento Celular/genética , Neoplasias Hepáticas/genética , ARN Mensajero/metabolismo , Secuencias Repetitivas de Ácidos Nucleicos , Animales , Secuencia de Bases , Northern Blotting , Carcinógenos/farmacología , Carcinoma Hepatocelular/inducido químicamente , Dimetilnitrosamina/farmacología , Hibridación in Situ , Neoplasias Hepáticas/inducido químicamente , Masculino , Datos de Secuencia Molecular , Conformación de Ácido Nucleico , Radioisótopos de Fósforo , ARN sin Sentido , Ratas , Ratas Sprague-Dawley , Tioacetamida/farmacología , Factores de Tiempo
9.
Am J Vet Res ; 40(8): 1078-81, 1979 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-43108

RESUMEN

With 120 minutes of pneumatic tourniquet application to the distal extremity in the horse, the following effects were noted in the tourniqueted limb vein (TLV): (i) local venous acidemia, (ii) increase in serum K+ concentrations, (iii) minimal changes in plasma total solids, Na+, or osmolality, and (iv) apparent reduction in hematocrit values when compared with the same measurements in the control leg. Tourniquet release after 120 minutes produced a prompt return to base line for PCV and PO2 in the TLV; however, pH, PCO2 and K+ values in the TLV required 10 to 15 minutes to reach base line (TLV or control leg vein).


Asunto(s)
Caballos/fisiología , Torniquetes/veterinaria , Animales , Sangre , Análisis de los Gases de la Sangre , Presión Sanguínea , Electrólitos/sangre , Extremidades , Caballos/sangre , Concentración de Iones de Hidrógeno , Concentración Osmolar
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