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In the present work, we focus on the cases of two-site (dimer) and three-site (trimer) configurations, i.e. oligomers, respecting the parity-time (PT) symmetry, i.e. with a spatially odd gain-loss profile. We examine different types of solutions of such configurations with linear and nonlinear gain/loss profiles. Solutions beyond the linear PT-symmetry critical point as well as solutions with asymmetric linearization eigenvalues are found in both the nonlinear dimer and trimer. The latter feature is absent in linear PT-symmetric trimers, while both of them are absent in linear PT-symmetric dimers. Furthermore, nonlinear gain/loss terms enable the existence of both symmetric and asymmetric solution profiles (and of bifurcations between them), while only symmetric solutions are present in the linear PT-symmetric dimers and trimers. The linear stability analysis around the obtained solutions is discussed and their dynamical evolution is explored by means of direct numerical simulations. Finally, a brief discussion is also given of recent progress in the context of PT-symmetric quadrimers.
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We introduce a general model which augments the one-dimensional nonlinear Schrödinger (NLS) equation by nonlinear-diffraction terms competing with the linear diffraction. The new terms contain two irreducible parameters and admit a Hamiltonian representation in a form natural for optical media. The equation serves as a model for spatial solitons near the supercollimation point in nonlinear photonic crystals. In the framework of this model, a detailed analysis of the fundamental solitary waves is reported, including the variational approximation (VA), exact analytical results, and systematic numerical computations. The Vakhitov-Kolokolov (VK) criterion is used to precisely predict the stability border for the solitons, which is found in an exact analytical form, along with the largest total power (norm) that the waves may possess. Past a critical point, collapse effects are observed, caused by suitable perturbations. Interactions between two identical parallel solitary beams are explored by dint of direct numerical simulations. It is found that in-phase solitons merge into robust or collapsing pulsons, depending on the strength of the nonlinear diffraction.
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We study the existence and stability of localized modes in the two-dimensional (2D) nonlinear Schrödinger/Gross-Pitaevskii (NLS/GP) equation with a symmetric four-well potential. Using the corresponding four-mode approximation, we trace the parametric evolution of the trapped stationary modes, starting from the linear limit, and thus derive a complete bifurcation diagram for families of the stationary modes. This provides the picture of spontaneous symmetry breaking in the fundamental 2D setting. In a broad parameter region, the predictions based on the four-mode decomposition are found to be in good agreement with full numerical solutions of the NLS/GP equation. Stability properties of the stationary states coincide with those suggested by the corresponding discrete model in the large-amplitude limit. The dynamics of unstable modes is explored by means of direct simulations. Finally, in addition to the full analysis for the case of the self-attractive nonlinearity, the bifurcation diagram for the case of self-repulsion is briefly considered too.
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Algoritmos , Luz , Modelos Teóricos , Dinámicas no Lineales , Fotones , Teoría Cuántica , Simulación por ComputadorRESUMEN
BACKGROUND: There is increasing evidence that high-risk human papilloma virus (HPV) is involved in cancers in addition to cervical cancer. For example, it is generally accepted that HPV has a role in a significant proportion of head and neck tumours, and it has long been hypothesised that hormone dependent oncogenic viruses, such as HPV may have causal roles in some human breast cancers. A number of reports have identified HPV DNA in breast tissue and breast cancer specimens, but these rely on standard polymerase chain reaction (PCR), which is criticised for its propensity for contamination. METHODS: We have used two different technologies, in situ and standard PCR (with sequencing), and histology based on light microscopy. RESULTS: We unambiguously demonstrate the presence of high-risk HPV in the cells of breast cancer specimens and breast cancer cell lines. In addition, we also show that the oncogenic characteristics of HPV associated breast cancer are very similar to HPV-associated cervical cancer. Specifically, that putative koilocytes are present in some HPV associated breast cancers. INTERPRETATION: The above observations indicate a likely causal role for high-risk HPV in human breast cancer and offer the possibility of primary prevention of some breast cancers by vaccination against HPV.
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Neoplasias de la Mama/virología , Papillomaviridae/aislamiento & purificación , Secuencia de Bases , Neoplasias de la Mama/etiología , Neoplasias de la Mama/patología , Línea Celular Tumoral , ADN Viral/análisis , Femenino , Humanos , Datos de Secuencia Molecular , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: High-risk human papilloma viruses (HPVs) are candidates as causal viruses in breast cancer. The scientific challenge is to determine whether HPVs are causal and not merely passengers or parasites. Studies of HPV-related koilocytes in breast cancer offer an opportunity to address this crucial issue. Koilocytes are epithelial cells characterised by perinuclear haloes surrounding condensed nuclei and are commonly present in cervical intraepithelial neoplasia. Koilocytosis is accepted as pathognomonic (characteristic of a particular disease) of HPV infection. The aim of this investigation is to determine whether putative koilocytes in normal and malignant breast tissues are because of HPV infection. METHODS: Archival formalin-fixed normal and malignant breast specimens were investigated by histology, in situ PCR with confirmation of the findings by standard PCR and sequencing of the products, plus immunohistochemistry to identify HPV E6 oncoproteins. RESULTS: human papilloma virus-associated koilocytes were present in normal breast skin and lobules and in the breast skin and cancer tissue of patients with ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDCs). INTERPRETATION: As koilocytes are known to be the precursors of some HPV-associated cervical cancer, it follows that HPVs may be causally associated with breast cancer.
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Neoplasias de la Mama/etiología , Células Epiteliales/patología , Papillomaviridae/aislamiento & purificación , Lesiones Precancerosas/etiología , Mama/virología , Neoplasias de la Mama/patología , Neoplasias de la Mama/virología , Femenino , Humanos , Carga ViralRESUMEN
Adoptive immunotherapy using autologous Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (auto-CTL) can regress posttransplant lymphoproliferative disorders (PTLD). Widespread applicability of auto-CTL remains constrained. Generation is time-consuming, and auto-CTL cannot be established in patients treated with the B-cell depleting antibody rituximab. By contrast, pregenerated allogeneic CTL (allo-CTL) offers immediate accessibility. Allo-CTL has previously shown efficacy in "early" polyclonal- PTLD. We treated three patients with aggressive, advanced monoclonal-PTLD following solid-organ transplantation. All were refractory to at least three prior therapies. Despite HLA disparity, there was negligible toxicity, with early in vivo antiviral efficacy and reconstitution of EBV peptide-specific immunity. Two patients attained complete remission (CR). One remains in CR 17 months following therapy, coincident with persistence of donor-derived tumor targeted EBV-specific CTL; the other died of non-PTLD related pathology. In the third patient, autopsy demonstrated homing of allo-CTL at the tumor site. Larger prospective studies of EBV-specific allo-CTL in PTLD are warranted.
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Trasplante de Corazón/efectos adversos , Inmunoterapia Adoptiva/métodos , Trasplante de Riñón/efectos adversos , Trasplante de Pulmón/efectos adversos , Trastornos Linfoproliferativos/inmunología , Trastornos Linfoproliferativos/terapia , Adolescente , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Femenino , Trasplante de Corazón/inmunología , Herpesvirus Humano 4/inmunología , Humanos , Trasplante de Riñón/inmunología , Trasplante de Pulmón/inmunología , Persona de Mediana Edad , Receptores Mensajeros de Linfocitos/inmunología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/patología , Carga ViralAsunto(s)
Neoplasias de la Mama/etiología , Enfermedades Virales de Transmisión Sexual/etiología , Australia/epidemiología , Neoplasias de la Mama/epidemiología , Femenino , Humanos , Persona de Mediana Edad , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Enfermedades Virales de Transmisión Sexual/epidemiologíaRESUMEN
In this work, we show a mathematical model for the angiogenesis by endothelial cells. We present the model at the level of partial differential equations, describing the spatiotemporal evolution of the cell population, the extracellular matrix macromolecules, the proteases, the tumor angiogenic factors, and the possible presence of inhibitors. We mainly focus, however, on a complementary, more physiologically realistic, hybrid approach in which the cells are treated as individual particles. We examine the model numerically in two-dimensional settings, discussing its comparison with experimental results.
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Modelos Biológicos , Neoplasias/irrigación sanguínea , Neovascularización Patológica/patología , Inhibidores de la Angiogénesis/fisiología , Proteínas Angiogénicas/fisiología , Animales , Células Endoteliales/patología , Endotelio Vascular/patología , Proteínas de la Matriz Extracelular/fisiología , Humanos , Neovascularización Patológica/tratamiento farmacológico , Péptido Hidrolasas/fisiologíaRESUMEN
In this paper, we examine in detail the principal branches of solutions that arise in vector discrete models with nonlinear intercomponent coupling and four wave mixing. The relevant four branches of solutions consist of two single mode branches (transverse electric and transverse magnetic) and two mixed mode branches, involving both components (linearly polarized and elliptically polarized). These solutions are obtained explicitly and their stability is analyzed completely in the anticontinuum limit (where the nodes of the lattice are uncoupled), illustrating the supercritical pitchfork nature of the bifurcations that give rise to the latter two, respectively, from the former two. Then the branches are continued for finite coupling constructing a full two-parameter numerical bifurcation diagram of their existence. Relevant stability ranges and instability regimes are highlighted and, whenever unstable, the solutions are dynamically evolved through direct computations to monitor the development of the corresponding instabilities. Direct connections to the earlier experimental work of Meier [Phys. Rev. Lett., 91, 143907 (2003)] that motivated the present work are given.
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BACKGROUND: Mouse mammary tumour virus (MMTV) has a proven role in breast carcinogenesis in wild mice and genetically susceptible in-bred mice. MMTV-like env gene sequences, which indicate the presence of a replication-competent MMTV-like virus, have been identified in some human breast cancers, but rarely in normal breast tissues. However, no evidence for a causal role of an MMTV-like virus in human breast cancer has emerged, although there are precedents for associations between specific histological characteristics of human cancers and the presence of oncogenic viruses. AIM: To investigate the possibility of an association between breast cancer and MMTV-like viruses. METHODS: Histological characteristics of invasive ductal human breast cancer specimens were compared with archival MMTV-associated mammary tumours from C3H experimental mice. The presence of MMTV-like env DNA sequences in the human breast cancer specimens was determined by polymerase chain reaction and confirmed by Southern hybridisation. RESULTS: MMTV-like env gene sequences were identified in 22 of 59 (37.3%) human breast cancer specimens. Seventeen of 43 (39.5%) invasive ductal carcinoma breast cancer specimens and 4 of 16 (25%) ductal carcinoma in situ specimens had some histological characteristics, which were similar to MMTV-associated mouse mammary tumours. However, these similarities were not associated with the presence or absence of MMTV-like gene sequences in the human breast tumour specimens. A significant (p = 0.05) correlation was found between the grade of the human breast cancer and similarity to the mouse mammary tumours. The lower the grade, the greater the similarity. CONCLUSION: Some human breast cancer specimens, in which MMTV-like env DNA sequences have been identified, were shown to have histological characteristics (morphology) similar to MMTV-associated mouse mammary tumours. These observations are compatible with, but not conclusive of, an association between the presence of MMTV-like env DNA sequences and some human breast cancers.
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Neoplasias de la Mama/virología , Carcinoma Ductal de Mama/virología , Carcinoma Intraductal no Infiltrante/virología , Virus del Tumor Mamario del Ratón/aislamiento & purificación , Animales , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Intraductal no Infiltrante/patología , ADN Viral/análisis , Femenino , Humanos , Neoplasias Mamarias Animales/patología , Neoplasias Mamarias Animales/virología , Virus del Tumor Mamario del Ratón/genética , Ratones , Ratones Endogámicos C3H , Reacción en Cadena de la Polimerasa/métodos , Infecciones por Retroviridae/complicaciones , Infecciones Tumorales por Virus/complicaciones , Proteínas del Envoltorio Viral/análisisRESUMEN
Human papilloma viruses (HPVs) are accepted as being carcinogenic in human cervical and anogenital cancers. The suspicion that HPVs may also have a role in human breast cancer is based on the identification of HPVs in human breast tumours and the immortalisation of normal human breast cells by HPV types 16 and 18. For this investigation, DNA that had been previously extracted and fresh frozen at -70 degrees C from 50 unselected invasive ductal breast cancer specimens were screened by polymerase chain reaction (PCR) for HPV type 16, 18 and 33 gene sequences. We show that HPV 18 gene sequences are present in DNA extracted from breast tumours in Australian women. Overall, 24 (48%) of the 50 samples were HPV positive. Overall no correlations with tumour grade, patient survival, steroid receptor status, ERB-2, p53 expression and mutation were observed. Human papilloma viruses may have a role in human breast cancer. We speculate that HPVs may be transmitted by hand from the female perineum to the breast.
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Neoplasias de la Mama/virología , ADN Viral/análisis , Papillomaviridae/genética , Papillomaviridae/patogenicidad , Secuencia de Bases , Carcinoma Ductal de Mama , Femenino , Humanos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Análisis de SupervivenciaRESUMEN
The effect of transepithelial solute, i.e., sodium chloride, backleak is taken into consideration in the spatiotemporal evolution of the chloride concentration along the thick ascending limb of a single nephron. The importance of the mechanism and of its mathematical modeling is argued on physiological grounds. The backleak "strength" is found to significantly modify the threshold for the appearance of temporally oscillatory behavior in the chloride concentration in the thick ascending limb which has previously been experimentally observed in normotensive rats.
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Biofisica/métodos , Nefronas/patología , Animales , Transporte Biológico Activo , Epitelio/patología , Tasa de Filtración Glomerular , Riñón/patología , Modelos Biológicos , Modelos Estadísticos , Nefronas/metabolismo , Oscilometría , Ratas , Cloruro de Sodio/metabolismoRESUMEN
When cervical carcinoma cells were monitored for apoptotic signals, HPV18(+) lines were found to be highly sensitive to agonistic CD95 antibodies or recombinant CD95 ligands after co-exposure with CHX (CD95(S)). In contrast, HPV16(+) cervical carcinoma cells and HPV16-immortalized non-malignant human keratinocytes were CD95-resistant (CD95(R)) under equivalent conditions. Somatic cell hybridization between CD95(S) and CD95(R) cervical carcinoma cell lines revealed that CD95 sensitivity was a dominant trait, which could be correlated with abundant c-Myc and low Bcl-X(L) expression. Although CD95(R) cervical carcinoma cells expressed even higher levels of p53 and CD95 receptor at the surface, resistance could be attributed to the inability to form a functional DISC, necessary for successful transmission of the apoptogenic response. These data indicate that resistance to apoptotic stimuli represents an important immunological escape mechanism during virus-induced carcinogenesis.
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Apoptosis , Carcinoma/patología , Carcinoma/virología , Papillomaviridae/metabolismo , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Receptor fas/biosíntesis , Western Blotting , Caspasa 3 , Caspasa 8 , Caspasa 9 , Caspasas/metabolismo , Separación Celular , Cicloheximida/farmacología , Fragmentación del ADN , Regulación hacia Abajo , Electroforesis en Gel de Poliacrilamida , Activación Enzimática , Femenino , Citometría de Flujo , Células HeLa , Humanos , Células Jurkat , Ligandos , Potenciales de la Membrana , Mitocondrias/metabolismo , Fenotipo , Inhibidores de la Síntesis de la Proteína/farmacología , Proteínas Recombinantes/metabolismo , Sensibilidad y Especificidad , Factores de Tiempo , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/biosíntesis , Receptor fas/metabolismoRESUMEN
Integrase is an enzyme found in human immunodeficiency virus, which is required for the viral life cycle, yet has no human cellular homologue. For this reason, HIV integrase (IN) has become an important target for the development of new AIDS therapeutics. Irreversible affinity ligands have proven to be valuable tools for studying a number of enzyme and protein systems, yet to date there have been no reports of such affinity ligands for the study of IN. As an initial approach toward irreversible ligand design directed against IN, we appended isothiocyanate functionality onto caffeic acid phenethyl ester (CAPE), a known HIV integrase inhibitor. The choice of isothiocyanate as the reactive functionality, was based on its demonstrated utility in the preparation of affinity ligands directed against a number of other protein targets. Several isomeric CAPE isothiocyanates were prepared to explore the enzyme topography for reactive nitrogen and sulfur nucleophiles vicinal to the enzyme-bound CAPE. The preparation of these CAPE isothiocyanates, required development of new synthetic methodology which employed phenyl thiocarbamates as latent isothiocyanates which could be unmasked near the end of the synthetic sequence. When it was observed that beta-mercaptoethanol (beta-ME), which is required to maintain the catalytic activity of soluble IN (a F185KC280S mutant), reacted with CAPE isothiocyanate functionality to form the corresponding hydroxyethylthiocarbamate, a variety of mutant IN were examined which did not require the presence of beta-ME for catalytic activity. Although in these latter enzymes, CAPE isothiocyanate functionality was presumed to be present and available for acylation by IN nucleophiles, they were equally effective against Cys to Ser mutants. One conclusion of these studies, is that upon binding of CAPE to the integrase, nitrogen or sulfur nucleophiles may not be properly situated in the vicinity of the phenethyl aryl ring to allow reaction with and covalent modification of reactive functionality, such as isothiocyanate groups. The fact that introduction of the isothiocyanate group onto various positions of the phenethyl ring or replacement of the phenyl ring with naphthyl rings, failed to significantly affect inhibitory potency, indicates a degree of insensitivity of this region of the molecule toward structural modification. These findings may be useful in future studies concerned with the development and use of HIV-1 integrase affinity ligands.
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Ácidos Cafeicos/metabolismo , Integrasa de VIH/metabolismo , VIH-1/enzimología , Isotiocianatos/química , Sustitución de Aminoácidos , Secuencia de Bases , Ácidos Cafeicos/química , Cisteína/química , Ésteres , Integrasa de VIH/química , Duplicado del Terminal Largo de VIH , Ligandos , Espectroscopía de Resonancia Magnética , Oligodesoxirribonucleótidos , Serina/química , Espectrometría de Masa Bombardeada por Átomos VelocesAsunto(s)
ATPasas Transportadoras de Calcio , Segregación Cromosómica , Cromosomas Fúngicos/fisiología , Endopeptidasas , Ligasas , Chaperonas Moleculares/metabolismo , Proteínas/metabolismo , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Ubiquitina-Proteína Ligasas , Secuencia de Aminoácidos , Animales , Proteínas de Ciclo Celular/metabolismo , División Celular , Cromátides/metabolismo , Cisteína Endopeptidasas/metabolismo , Proteínas Fúngicas/metabolismo , Humanos , Chaperonas Moleculares/química , Complejos Multienzimáticos/metabolismo , Mutación , Neoplasias/etiología , Neoplasias/genética , Fragmentos de Péptidos/química , Fragmentos de Péptidos/metabolismo , Complejo de la Endopetidasa Proteasomal , Proteínas/química , Saccharomyces cerevisiae/citología , Separasa , Ubiquitinas/metabolismoRESUMEN
The E6 oncoprotein of human papillomaviruses (HPVs) that are associated with cervical cancer utilizes the cellular ubiquitin-protein ligase E6-AP to target the tumor suppressor p53 for degradation. In normal cells (i.e., in the absence of E6), p53 is also a target of the ubiquitin-proteasome pathway. Under these conditions, however, p53 degradation is mediated by Mdm2 rather than by E6-AP. Here we show in a mutational analysis that, surprisingly, the structural requirements of p53 to serve as a proteolytic substrate differ between E6 proteins derived from different HPV types and, as expected, between Mdm2 and E6 proteins in vitro and in vivo. Stable expression of such mutants in HPV-negative and HPV-positive cell lines demonstrates that in HPV-positive cancer cells, the E6-dependent pathway of p53 degradation is not only active but, moreover, is required for degradation of p53, whereas the Mdm2-dependent pathway is inactive. Because the p53 pathway was reported to be functional in HPV-positive cancer cells, this finding indicates clearly that the ability of the E6 oncoprotein to target p53 for degradation is required for the growth of HPV-positive cancer cells.
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Proteínas Nucleares , Proteínas Oncogénicas Virales/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Femenino , Semivida , Humanos , Proteínas Oncogénicas Virales/genética , Papillomaviridae/genética , Proteínas Proto-Oncogénicas c-mdm2 , Proteínas Recombinantes/metabolismo , Especificidad por Sustrato , Transfección , Células Tumorales Cultivadas , Ubiquitinas/metabolismo , Neoplasias del Cuello UterinoRESUMEN
Human papillomaviruses (HPVs) are causative agents of a number of malignancies in humans, including cervical cancer. Their tumorigenic potential is linked to expression of the viral E6/E7 genes which can interfere with normal cell cycle control by targeting p53, p21WAF1, p27KIP1, and pRb. We show here that nontumorigenic and tumorigenic HPV-positive keratinocytes (HPK) exhibit striking differences in the response of cell cycle regulatory genes towards transforming growth factor beta-beta1. Treatment with this agent led to an efficient induction of p53 and the growth-inhibitory p15INK4 and p21WAF1 genes only in nontumorigenic HPKs and was linked to an efficient reduction in viral E6/E7 oncogene expression. This was associated with increased pRb levels, exhibiting sustained hypophosphorylation, and a permanent growth arrest in the G1 phase of the cell cycle. In contrast, tumorigenic HPKs exhibited only a modest rise in p53 protein levels and a substantially reduced induction of the p15INK4 and p21WAF1 genes, which was linked to a lesser degree of viral oncogene repression. In addition, tumorigenic HPKs rapidly resumed cell growth after a transient G1 arrest, concomitantly with the reappearance of hyperphosphorylated pRb. These results support the notion that the progression of HPV-positive cells to a malignant phenotype is associated with increased resistance to growth inhibition by transforming growth factor-beta1. This is linked in the tumorigenic cells to a lack of persistent G1 arrest, inefficient induction of several cell cycle control genes involved in growth inhibition, and inefficient repression of the growth-promoting viral E6/E7 oncogenes.
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Ciclo Celular/efectos de los fármacos , Transformación Celular Viral , Queratinocitos/citología , Queratinocitos/virología , Papillomaviridae/fisiología , Factor de Crecimiento Transformador beta/farmacología , Northern Blotting , Western Blotting , Ciclo Celular/genética , Línea Celular Transformada , Transformación Celular Neoplásica , Regulación de la Expresión Génica , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/fisiologíaRESUMEN
Apoptosis of neuronal cells apparently plays a role in Alzheimer's disease (AD). The amyloid beta (Abeta) peptide derived from beta-amyloid precursor protein is found in AD brain in vivo and can induce apoptosis in vitro. While p53 accumulates in cells of AD brain, it is not known if p53 plays an active role in Abeta-induced apoptosis. We show here that inactivation of p53 in two experimental cell lines, either by expression of the papillomavirus E6 protein or by a shift to restrictive temperature, does not affect apoptosis induction by Abeta (25-35), indicating that Abeta induces apoptosis in a p53-independent manner.
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Péptidos beta-Amiloides/farmacología , Apoptosis/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Osteosarcoma/patología , Fragmentos de Péptidos/farmacología , Proteínas Represoras , Proteína p53 Supresora de Tumor/metabolismo , Animales , Células Cultivadas , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Ciclinas/metabolismo , Humanos , Queratinocitos/citología , Queratinocitos/metabolismo , Proteínas Oncogénicas Virales/genética , Proteínas Oncogénicas Virales/metabolismo , Osteosarcoma/metabolismo , Proteínas E7 de Papillomavirus , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Temperatura , Transfección , Proteína p53 Supresora de Tumor/antagonistas & inhibidores , Proteína p53 Supresora de Tumor/genética , Xenopus laevis , Proteína X Asociada a bcl-2RESUMEN
Comprehensive hematologic and biochemical analyses were conducted on blood from 23 male and 31 female clinically stable captive mugger crocodiles (Crocodylus palustris). Erythrocyte mean corpuscular volume (MCV), potassium, cholesterol, and calcium concentrations were significantly greater in juvenile males than in juvenile females, but no significant differences were determined between parameters of subadult males and subadult females. The mean WBC count and mean heterophil count were significantly higher in adult males than in adult females. Mean uric acid concentration was significantly greater in adult females than in males. Mean erythrocyte count was significantly higher in adults than in juveniles. Adult mean WBC and lymphocyte counts were significantly lower than those of both juveniles and subadults. Subadults had significantly lower mean eosinophil counts than both adults and juveniles. Subadults had significantly lower mean alkaline phosphatase activities than juveniles, whereas the adults had significantly lower aspartate aminotransferase and alanine aminotransferase activities than other groups. Lactate dehydrogenase activities were significantly lower for subadults than for juveniles and adults. Cholesterol concentrations were significantly higher for subadults and juveniles compared with adults. Triglyceride concentration was significantly lower for subadults and highest for juveniles. Glucose concentrations were significantly higher for adults. Blood urea nitrogen was significantly lower for subadults than for both adults and juveniles. Uric acid concentrations were significantly higher for juveniles than for the subadults and adults. The subadult animals also had a significantly lower potassium concentration. The results obtained were then compared with known values for other crocodilian species.