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The Levantine basin (LB) in the Southeastern Mediterranean Sea is a high-risk oil pollution hot spot owing to its dense maritime traffic and intense oil and gas exploration and exploitation activities. In February 2021 the Israeli LB shorelines were impacted by an exceptional tar pollution event (~550 tons; average distribution: ~3 kg tar m-1 front beach) of an unknown oil spill source. Here we report on the immediate numerical modelling assessment of the oil spill propagation and tar distribution; operational use of underwater gliders for tracking water column anomalies of dissolved polycyclic aromatic hydrocarbons (PAHs) and turbidity signals; the beached tar composition and amounts and the short-term response of the microbial population along the ~180 km shoreline. This pollution event emphasizes the need for improving the early warning systems for oil spills and implementing continuous operational monitoring at high-risk, ecologically sensitive and valuable resource areas like the Israeli LB waters.
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Contaminación por Petróleo , Hidrocarburos Policíclicos Aromáticos , Contaminantes Químicos del Agua , Monitoreo del Ambiente , Contaminación por Petróleo/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Mar Mediterráneo , Contaminantes Químicos del Agua/análisisRESUMEN
Chlamydia gallinacea is a recently described bacterial species in a genus known to infect and cause disease in animals and humans. Our report describes the identification of C. gallinacea infection in free-range laying chickens (Gallus gallus) in Australia, and the identification of C. gallinacea infection in a parrot, a wild Australian galah (Eolophus roseicapillus). There is currently little knowledge of the effects of C. gallinacea infection on avian hosts, but it has been linked to respiratory disease in humans and could potentially cause similar disease in other species. Our report highlights the need for further study and surveillance of Chlamydia species in both wild and domestic hosts in Australia.
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Enfermedades de las Aves/epidemiología , Enfermedades de las Aves/microbiología , Infecciones por Chlamydia/veterinaria , Chlamydia/aislamiento & purificación , Crianza de Animales Domésticos , Animales , Australia/epidemiología , Proteínas de la Membrana Bacteriana Externa/aislamiento & purificación , Pollos , Chlamydia/genética , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/microbiología , Femenino , Humanos , Loros , Enfermedades de las Aves de Corral , Victoria/epidemiologíaRESUMEN
The acquired kinase mutation JAK2V617F plays a central role in myeloproliferative neoplasms (MPNs). However, the mechanisms responsible for the malignant hematopoietic stem/progenitor cell (HSPC) expansion seen in patients with MPNs are not fully understood, limiting the effectiveness of current treatment. Endothelial cells (ECs) are an essential component of the hematopoietic niche, and they have been shown to express the JAK2V617F mutation in patients with MPNs. We show that the JAK2V617F-bearing vascular niche promotes the expansion of the JAK2V617F HSPCs in preference to JAK2WT HSPCs, potentially contributing to poor donor cell engraftment and disease relapse following stem cell transplantation. The expression of Chemokine (C-X-C motif) ligand 12 (CXCL12) and stem cell factor (SCF) were upregulated in JAK2V617F-bearing ECs compared to wild-type ECs, potentially accounting for this observation. We further identify that the thrombopoietin (TPO)/MPL signaling pathway is critical for the altered vascular niche function. A better understanding of how the vascular niche contributes to HSPC expansion and MPN development is essential for the design of more effective therapeutic strategies for patients with MPNs.
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Janus Quinasa 2/genética , Trastornos Mieloproliferativos/genética , Neoplasias/genética , Animales , Quimiocina CXCL12/genética , Células Endoteliales/metabolismo , Células Madre Hematopoyéticas/metabolismo , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mutación/genética , Receptores de Trombopoyetina/genética , Regulación hacia Arriba/genéticaRESUMEN
Stroke is a leading cause of death and disability. Effects of stroke include significant deficits in sensory-motor skills and cognitive abilities. At present, there are limited effective interventions for postacute stroke patients. In this preliminary research we studied a new noninvasive, very low intensity, low frequency, electromagnetic field treatment (VLIFE), targeting a neural network, on an in vivo stroke rat model. Eighteen rats were divided into three groups: sham (M1) and two treatment groups which were exposed to VLIFE treatment for 4 weeks, one using theta waves (M2) and another using beta waves (M3); all groups were followed up for an additional month. Results indicate that the M2 and M3 treated groups showed recovery of sensorimotor functional deficits, as demonstrated by Modified Neurological Severity Score and forelimb placement tests. Brain MRI imaging results show a decrease in perilesional edema and lateral ventricle widening in the treated groups. Fiber tracts' imaging, following VLIFE treatment, showed a higher white matter integrity compared to control. Histological findings support neural regeneration processes. Our data suggest that VLIFE treatment, targeting a specific functional neural network by frequency rather than location, promotes neuronal plasticity after stroke and, as a result, improves clinical recovery. Further studies will investigate the full potential of the treatment.
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A recent outbreak of Q fever was linked to an intensive goat and sheep dairy farm in Victoria, Australia, 2012-2014. Seventeen employees and one family member were confirmed with Q fever over a 28-month period, including two culture-positive cases. The outbreak investigation and management involved a One Health approach with representation from human, animal, environmental and public health. Seroprevalence in non-pregnant milking goats was 15% [95% confidence interval (CI) 7-27]; active infection was confirmed by positive quantitative PCR on several animal specimens. Genotyping of Coxiella burnetii DNA obtained from goat and human specimens was identical by two typing methods. A number of farming practices probably contributed to the outbreak, with similar precipitating factors to the Netherlands outbreak, 2007-2012. Compared to workers in a high-efficiency particulate arrestance (HEPA) filtered factory, administrative staff in an unfiltered adjoining office and those regularly handling goats and kids had 5·49 (95% CI 1·29-23·4) and 5·65 (95% CI 1·09-29·3) times the risk of infection, respectively; suggesting factory workers were protected from windborne spread of organisms. Reduction in the incidence of human cases was achieved through an intensive human vaccination programme plus environmental and biosecurity interventions. Subsequent non-occupational acquisition of Q fever in the spouse of an employee, indicates that infection remains endemic in the goat herd, and remains a challenge to manage without source control.
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Enfermedades de los Trabajadores Agrícolas/prevención & control , Brotes de Enfermedades/prevención & control , Enfermedades de las Cabras/prevención & control , Fiebre Q/prevención & control , Enfermedades de las Ovejas/prevención & control , Vacunación , Zoonosis/prevención & control , Adolescente , Adulto , Anciano , Enfermedades de los Trabajadores Agrícolas/epidemiología , Crianza de Animales Domésticos , Animales , Niño , Coxiella burnetii/genética , Coxiella burnetii/aislamiento & purificación , ADN Bacteriano/genética , ADN Bacteriano/metabolismo , Agricultores , Femenino , Genotipo , Enfermedades de las Cabras/epidemiología , Cabras , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Fiebre Q/epidemiología , Factores de Riesgo , Estudios Seroepidemiológicos , Ovinos , Enfermedades de las Ovejas/epidemiología , Victoria/epidemiología , Adulto Joven , Zoonosis/epidemiologíaRESUMEN
The transport and magnetic properties of correlated La0.53Sr0.47MnO3 ultrathin films, grown epitaxially on SrTiO3, show a sharp cusp at the structural transition temperature of the substrate. Using a combination of experiment and first principles theory we show that the cusp is a result of evanescent cross-interface coupling between the charge carriers in the film and a soft phonon mode in the SrTiO3, mediated through linked oxygen octahedral motions. The amplitude of the mode diverges at the transition temperature, and phonons are launched into the first few atomic layers of the film, affecting its electronic state.
RESUMEN
The electronic valence state of Mn in Pb(Zr0.2Ti0.8)O{3}/La{0.8}Sr{0.2}MnO{3} multiferroic heterostructures is probed by near edge x-ray absorption spectroscopy as a function of the ferroelectric polarization. We observe a temperature independent shift in the absorption edge of Mn associated with a change in valency induced by charge carrier modulation in the La0.8Sr0.2MnO3, demonstrating the electronic origin of the magnetoelectric effect. Spectroscopic, magnetic, and electric characterization shows that the large magnetoelectric response originates from a modified interfacial spin configuration, opening a new pathway to the electronic control of spin in complex oxide materials.
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We use SrTiO3/Si as a model system to elucidate the effect of the interface on ferroelectric behavior in epitaxial oxide films on silicon. Using both first-principles computations and synchrotron x-ray diffraction measurements, we show that structurally imposed boundary conditions at the interface stabilize a fixed (pinned) polarization in the film but inhibit ferroelectric switching. We demonstrate that the interface chemistry responsible for these phenomena is general to epitaxial silicon-oxide interfaces, impacting on the design of silicon-based functional oxide devices.
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We present the structure of the interface responsible for epitaxy of crystalline oxides on silicon. Using synchrotron x-ray diffraction, we observe a 2 x 1 unit cell reconstruction at the interface of BaO grown on Si(001) terminated with 1/2 ML of Sr. Since this symmetry is not present in bulk BaO or Si, only the interface contributes to diffracted intensity. First principles calculations accurately predict the observed diffraction and identify the structure of the BaO/Si interface, including the elemental composition and a sub-A rumpling due to epitaxial strain of the 7 adjacent BaO and Si layers.
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Alport syndrome, caused by mutations that interfere with the normal assembly of the alpha3alpha4alpha5(IV) collagen network in the glomerular basement membrane (GBM), is the most common inherited glomerular disease leading to renal failure. A detailed knowledge of the underlying pathogenic mechanisms is necessary for developing new, more specific, and effective therapeutic strategies aimed at delaying the onset and slowing disease progression. Studies of several dog and mouse models of Alport syndrome have significantly enhanced our understanding of the disease mechanisms and provided systems for testing potential therapies. In the most widely used Col4a3-/- mouse models of autosomal-recessive Alport syndrome (ARAS), the genetic background strongly affects renal survival. One contributing factor may be the strong ectopic deposition of alpha5alpha6(IV) collagen in the GBM of Col4a3-/- mice on the C57BL/6J background, which is almost undetectable on the 129/Sv background. This isoform 'switch' has not been observed in human ARAS, although it had been reported in the dog model of ARAS. In human patients as well as dog and mouse models of X-linked Alport syndrome, the alpha3-alpha6(IV) collagen chains are absent from the GBM. These biochemical differences among Alport animal models provide an opportunity to determine how the molecular makeup of the GBM affects the glomerular function. At the same time, potentially confounding influences of characteristics unique to a particular strain or model should be carefully considered in the design of studies aiming to define key events underlying the pathobiology of Alport glomerular disease.
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Modelos Animales de Enfermedad , Nefritis Hereditaria/genética , Animales , Expresión Génica , RatonesRESUMEN
UNLABELLED: The effect of ritonavir 400 mg/saquinavir 400 mg twice daily on the stereoselective pharmacokinetics of methadone was examined in 12 HIV-infected, methadone-using study subjects. DESIGN: A 24-hour methadone pharmacokinetic study was performed before antiretroviral therapy was begun and after 15 days of therapy. Methadone concentration was measured by a chiral plasma assay because the drug is administered as a racemic mixture of R- and S-methadone, but only the R-isomer is active. Both changes in plasma protein binding and changes in objective and subjective opioid effect were monitored. RESULTS: Ritonavir/saquinavir administration was associated with 40% decrease in total S-methadone AUC0-24hr and 32% decrease in R-methadone area under the curve (AUC)0-24hr, and both changes were statistically significant (p =.001 for both). When AUC was corrected for the changes in protein binding induced by ritonavir/saquinavir, R-methadone free AUC0-24hr decreased 19.6% whereas the S-methadone decreased 24.6%, neither of these changes was statistically significant (p =.129 and p =.0537, respectively). This change in methadone exposure was not associated with any evidence of withdrawal from narcotics and no modification of methadone dose was required. CONCLUSIONS: Our data indicate that ritonavir/saquinavir administration is associated with induction of metabolism of methadone but this is greater for the inactive S-methadone. However, approximately 37% of the decrease in the total R-methadone exposure can be explained by protein binding displacement. Ritonavir/saquinavir can be used in HIV-infected people taking methadone without routine dose adjustments.
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Inhibidores de la Proteasa del VIH/administración & dosificación , Metadona/farmacocinética , Narcóticos/farmacocinética , Ritonavir/administración & dosificación , Saquinavir/administración & dosificación , Adulto , Interacciones Farmacológicas , Femenino , Infecciones por VIH/tratamiento farmacológico , VIH-1/fisiología , Humanos , Masculino , Metadona/uso terapéutico , Persona de Mediana Edad , Narcóticos/uso terapéutico , Ritonavir/sangre , Saquinavir/sangre , Estereoisomerismo , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/rehabilitaciónRESUMEN
Most patients with autosomal dominant polycystic kidney disease (ADPKD) harbor mutations truncating polycystin-1 (PC1) or polycystin-2 (PC2), products of the PKD1 and PKD2 genes, respectively. A third member of the polycystin family, polycystin-L (PCL), was recently shown to function as a Ca(2+)-modulated nonselective cation channel. More recently, PC2 was also shown to be a nonselective cation channel with comparable properties to PCL, though the membrane targeting of PC2 likely varies with cell types. Here we show that PC2 expressed heterologously in Xenopus oocytes is targeted to intracellular compartments. By contrast, a truncated form of mouse PC2 corresponding to a naturally occurring human mutation R742X is targeted predominantly to the plasma membrane where it mediates K(+), Na(+), and Ca(2+) currents. Unlike PCL, the truncated form does not display Ca(2+)-activated transport activities, possibly due to loss of an EF-hand at the C-terminus. We propose that PC2 forms ion channels utilizing structural components which are preserved in the R742X form of the protein. Implications for epithelial cell signaling are discussed.
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Sustitución de Aminoácidos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Mutación/genética , Secuencias de Aminoácidos/fisiología , Animales , Calcio/metabolismo , Calcio/farmacocinética , Compartimento Celular/fisiología , Membrana Celular/metabolismo , Células Cultivadas , Líquido Intracelular/metabolismo , Canales Iónicos/fisiología , Potenciales de la Membrana/fisiología , Ratones , Microinyecciones , Técnicas de Placa-Clamp , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/metabolismo , Transporte de Proteínas/fisiología , ARN Mensajero/administración & dosificación , ARN Mensajero/metabolismo , Canales Catiónicos TRPP , XenopusRESUMEN
Mutations in polycystins-1 and -2 (PC1 and PC2) cause autosomal dominant polycystic kidney disease (ADPKD), which is characterized by progressive development of epithelial renal cysts, ultimately leading to renal failure. The functions of these polycystins remain elusive. Here we show that PC2 is a Ca(2+)-permeable cation channel with properties distinct from any known intracellular channels. Its kinetic behavior is characterized by frequent transitions between closed and open states over a wide voltage range. The activity of the PC2 channel is transiently increased by elevating cytosolic Ca(2+). Given the predominant endoplasmic reticulum (ER) location of PC2 and its unresponsiveness to the known modulators of mediating Ca(2+) release from the ER, inositol-trisphosphate (IP(3)) and ryanodine, these results suggest that PC2 represents a novel type of channel with properties distinct from those of the other Ca(2+)-release channels. Our data also show that the PC2 channel can be translocated to the plasma membranes by defined chemical chaperones and proteasome modulators, suggesting that in vivo, it may also function in the plasma membrane under specific conditions. The sensitivity of the PC2 channel to changes of intracellular Ca(2+) concentration is deficient in a mutant found in ADPKD patients. The dysfunction of such mutants may result in defective coupling of PC2 to intracellular Ca(2+) homeostasis associated with the pathogenesis of ADPKD.
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Canales de Calcio/fisiología , Calcio/metabolismo , Homeostasis/fisiología , Proteínas de la Membrana/fisiología , Enfermedades Renales Poliquísticas/fisiopatología , Animales , Canales de Calcio/genética , Clonación Molecular , ADN Complementario , Humanos , Inmunohistoquímica , Proteínas de la Membrana/genética , Ratones , Canales Catiónicos TRPP , XenopusRESUMEN
Tissue-specific expression patterns of the paired type IV collagen genes COL4A5 and COL4A6 form the basis for organ involvement in X-linked Alport syndrome, a disorder in which these genes are mutated. We investigated the proximal promoter region of COL4A5 and COL4A6 using glomerular visceral epithelial cells, in which COL4A5 alone is transcribed; keratinocytes, in which the genes are co-transcribed; and additional model cell lines. By RNase protection assays, the intergenic region is 292 base pairs. Transcription start sites for two 5' splice variants of COL4A6 are 1 kilobase apart. Transient transfections with reporter gene constructs revealed that the minimal promoters for COL4A5 and COL4A6 are within 100 base pairs of their respective transcription start sites and are functionally distinct. In further transfection, gel shift and footprinting assays, we defined a bidirectional positive regulatory element, which functions in several cell types, but not in glomerular visceral epithelial cells selectively transcribing COL4A5. The existence of separate promoters for COL4A5 and COL4A6 permits fine control over their expression. Activation through the bidirectional element can bring about co-expression of the genes, exploiting their paired arrangement. Features of the proximal promoter region frame its roles in a hierarchy regulating type IV collagen gene expression.
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Colágeno/genética , Regulación de la Expresión Génica/genética , Regiones Promotoras Genéticas , Transcripción Genética/genética , Secuencia de Bases , Línea Celular , ADN , Huella de ADN , Genes Reporteros , Humanos , Datos de Secuencia Molecular , Secuencias Reguladoras de Ácidos NucleicosRESUMEN
Polycystic kidney diseases are genetic disorders in which the renal parenchyma is progressively replaced by fluid-filled cysts. Two members of the polycystin family (polycystin-1 and -2) are mutated in autosomal dominant polycystic kidney disease (ADPKD), and polycystin-L is deleted in mice with renal and retinal defects. Polycystins are membrane proteins that share significant sequence homology, especially polycystin-2 and -L (50% identity and 71% similarity). The functions of the polycystins remain unknown. Here we show that polycystin-L is a calcium-modulated nonselective cation channel that is permeable to sodium, potassium and calcium ions. Patch-clamp experiments revealed single-channel activity with a unitary conductance of 137 pS. Channel activity was substantially increased when either the extracellular or intracellular calcium-ion concentration was raised, indicating that polycystin-L may act as a transducer of calcium-mediated signalling in vivo. Its large single-channel conductance and regulation by calcium ions distinguish it from other structurally related cation channels.
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Canales de Calcio/metabolismo , Calcio/metabolismo , Glicoproteínas de Membrana/metabolismo , Fosfoproteínas/metabolismo , Animales , Canales de Calcio/genética , Señalización del Calcio , Cationes Bivalentes/metabolismo , Permeabilidad de la Membrana Celular , Quelantes/farmacología , Clonación Molecular , Ácido Egtácico/farmacología , Electrofisiología , Humanos , Glicoproteínas de Membrana/genética , Técnicas de Placa-Clamp , Fosfoproteínas/genética , Enfermedades Renales Poliquísticas/metabolismo , Receptores de Superficie Celular , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Tapsigargina/farmacología , XenopusAsunto(s)
Enfermedad de Newcastle/patología , Enfermedades de las Aves de Corral/patología , Infecciones del Sistema Respiratorio/veterinaria , Animales , Antígenos Virales/análisis , Australia/epidemiología , Pollos , Brotes de Enfermedades/veterinaria , Técnica del Anticuerpo Fluorescente Indirecta , Enfermedad de Newcastle/epidemiología , Enfermedades de las Aves de Corral/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/patología , SíndromeRESUMEN
Deletions encompassing the 5' termini of the paired type IV collagen genes COL4A5 and COL4A6 on chromosome Xq22 give rise to Alport syndrome (AS) and associated diffuse leiomyomatosis (DL), a syndrome of disseminated smooth-muscle tumors involving the esophagus, large airways, and female reproductive tract. In this study, we report isolation and characterization of two deletion junctions. The first, in a patient described elsewhere, arose by a nonhomologous recombination event fusing a LINE-1 (L1) repetitive element in intron 1 of COL4A5 to intron 2 of COL4A6, resulting in a 13.4-kb deletion. The second, in a previously undescribed family, arose by unequal homologous recombination between the same L1 and a colinear L1 element in intron 2 of COL4A6, resulting in a>40-kb deletion. L1 elements have contributed to the emergence of this locus as a site of frequent recombinations by diverse mechanisms. These give rise to AS-DL by disruption of type IV collagen and perhaps other as yet unidentified genes, evidenced by deletions as small as 13.4 kb.
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Elementos de Nucleótido Esparcido Largo , Nefritis Hereditaria/genética , Cromosoma X , Adulto , Secuencia de Bases , Biopsia , Colágeno/genética , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Nefritis Hereditaria/inmunología , Nefritis Hereditaria/patología , Linaje , Piel/patologíaRESUMEN
Transforming growth factor beta1 (TGF-beta1) is a cytokine known to play a key role in the control of cell growth. TGF-beta1 potently inhibits the proliferation of human and rodent-derived epithelial cells. Colonic precancerous and moderately differentiated cancer cells are responsive to TGF-beta1, whereas malignant colon cancer cells are resistant to the inhibitory action of the cytokine. These observations have been derived exclusively from in vitro studies. Therefore, the main aim of our study was to determine whether TGF-beta1 exerts a growth-restraining action on colon carcinogenesis in vivo. TGF-beta1 was sequestered into ethylene acetate copolymer matrices and "loaded" preparations were implanted intraperitoneally (i.p.) in rats. One week later, the animals were treated with dimethylhydrazine (DMH), a colon procarcinogen. Empty matrices devoid of TGF-beta1 but containing bovine serum albumin (BSA) carrier served as the appropriate control preparations. The number of aberrant crypt foci (ACF), considered to be preneoplastic lesions of the colon, was scored. Tumor formation and size were assessed at the appropriate times. TGF-beta1 released in a sustained manner from copolymer matrices: (i) markedly inhibited colonic ACF formation and the number of aberrant crypts and (ii) significantly reduced colonic tumor formation and size.
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Neoplasias del Colon/prevención & control , Lesiones Precancerosas/prevención & control , Factor de Crecimiento Transformador beta/administración & dosificación , 1,2-Dimetilhidrazina , Animales , Implantes de Medicamentos , Masculino , Polímeros/administración & dosificación , Ratas , Receptores de Factores de Crecimiento Transformadores beta/análisisRESUMEN
COL4A5 mutations causing X-linked Alport syndrome (XLAS) are frequently associated with absence of the alpha3, alpha4,alpha5 and alpha6 chains of type IV collagen from basement membranes and increased amounts of the alpha1(IV) and alpha2(IV) chains in glomerular basement membrane. Although many COL4A5 mutations have been described in XLAS, the mechanisms by which these mutations influence the basement membrane appearance of chains other than alpha5(IV) remain poorly understood. In this study, we used dermal fibroblasts from eight normal individuals and nine males with XLAS to test the hypotheses that COL4A5 mutations increase transcription of COL4A1 and suppress transcription of COL4A6. Ribonuclease protection assays revealed that alpha1(IV), alpha5(IV) and alpha6(IV) transcripts were expressed in cultures of dermal fibroblasts. The mRNA levels for alpha1(IV) in eight of nine patients with XLAS were not increased compared to controls; one patient with a large COL4A5 deletion showed significant elevation of alpha1(IV) mRNA levels. No differences in steady-state mRNA levels for alpha6(IV) were found when XLAS fibroblasts were compared with controls, even though little or no alpha6(IV) protein was detectable at the dermal-epidermal junction by immunofluorescence study. This finding suggests that post-transcriptional events account for the absence of alpha6(IV) in the Alport dermal-epidermal junction.
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Colágeno/biosíntesis , Nefritis Hereditaria/metabolismo , ARN Mensajero/biosíntesis , Piel/metabolismo , Adolescente , Adulto , Células Cultivadas , Colágeno/genética , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Persona de Mediana Edad , Mutación , Nefritis Hereditaria/genética , Piel/patologíaRESUMEN
OBJECTIVE: The present study was designed to prospectively evaluate the intraperitoneal pressure, as well as clinical and hemodynamic effects of total paracentesis, as palliation of symptomatic ascites in ovarian cancer patients. METHODS: Prospective study of 35 sequential total paracenteses was performed using a Veres cannula on patients with advanced recurrent ovarian cancer with symptomatic tense ascites. Relevant clinical symptoms and patient well-being were evaluated. Vital signs, abdominal parameters, and hydrostatic intraperitoneal pressure were recorded before, during, and after the procedure. RESULTS: Intraperitoneal pressure dropped from 30 +/- 7 cmH2O before paracentesis to 13 +/- 6 cmH2O after the procedure (P < 0.0001). Marked symptomatic improvement was observed in all patients (89% complete relief, 11% partial relief), while all the patients tolerated the procedure well without any complications. The mean volume of ascitic fluid removed was 4800 ml. Mean respiratory rate and mean heart rate were both significantly decreased following the procedure (29.3 to 21.4 respirations per min and 101.5 to 93.6 beats per min, respectively). Mean systolic blood pressure mildly decreased (6.6 mmHg), while the mean diastolic blood pressure did not significantly change. None of the patients presented signs or symptoms of hypovolemia during or after the total paracentesis. CONCLUSIONS: Measurement of intraperitoneal pressures during total paracentesis for tense ascites in ovarian cancer patients indicated that the severity of symptoms correlated with the intraperitoneal pressure prior to paracentesis, but not with the volume of ascites. Intraperitoneal pressures measured following total paracentesis in patients with ovarian cancer were similar to the baseline intraperitoneal pressure measured in patients undergoing peritoneal dialysis.