RESUMEN
BACKGROUND: Ebola virus disease is a public health emergency of international concern, and enormous efforts are being made in the development of vaccines and therapies. Ebola virus convalescent plasma is a promising anti-infective treatment of Ebola virus disease. Therefore, we developed and implemented a pathogen-reduced Ebola virus convalescent plasma concept in accordance with national, European and global regulatory framework. MATERIALS AND METHODS: Ebola virus convalescent plasma manufacture and distribution was managed by a collection centre, two medical centres and an expert group from the European Blood Alliance. Ebola virus convalescent plasma was collected twice with an interval of 61 days from a donor recovering from Ebola virus disease in Germany. After pathogen reduction, the plasma was analysed for Ebola virus-specific immunoglobulin G (IgG) antibodies and its Ebola virus neutralizing activity. RESULTS: Convalescent plasma could be collected without adverse events. Anti-Ebola virus IgG titres and Ebola-specific neutralizing antibodies in convalescent plasma were only slightly reduced after pathogen reduction treatment with S59 amotosalen/UVA. A patient in Italy with Ebola virus disease was treated with convalescent plasma without apparent adverse effects. DISCUSSION: As proof of principle, we describe a concept and practical implementation of pathogen-reduced Ebola virus convalescent plasma manufacture, quality control and its clinical application to an Ebola virus disease patient.
Asunto(s)
Anticuerpos Neutralizantes/aislamiento & purificación , Ebolavirus/inmunología , Fiebre Hemorrágica Ebola/prevención & control , Inmunoglobulina G/aislamiento & purificación , Adulto , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/uso terapéutico , Donantes de Sangre , Convalecencia , Furocumarinas/farmacología , Alemania , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina G/uso terapéutico , Masculino , Persona de Mediana Edad , Fármacos Fotosensibilizantes/farmacología , Control de Calidad , Rayos Ultravioleta , Inactivación de Virus/efectos de los fármacos , Inactivación de Virus/efectos de la radiaciónRESUMEN
In Drosophila, five "terminal" polarity genes must be active in females in order for them to produce embryos with normal anterior and posterior ends. Hypoactivity mutations in one such gene, torso, result in the loss of the most posterior domain of fushi tarazu expression and the terminal cuticular structures. In contrast, a torso hyperactivity mutation causes the loss of central fushi tarazu expression and central cuticular structures. Cytoplasmic leakage, transplantation, and temperature-shift experiments suggest that the latter effect is caused by abnormal persistence of the torso product in the central region of the embryo during early development. Thus, the amount and timing of torso activity is key to distinguishing the central and terminal regions of the embryo. Mutations in the tailless terminal gene act as dominant maternal suppressors of the hyperactive torso allele, indicating that the torso product acts through, or in concert with, the tailless product.
Asunto(s)
Drosophila/genética , Abdomen , Alelos , Animales , Citoplasma/fisiología , Drosophila/anatomía & histología , Drosophila/embriología , Femenino , Regulación de la Expresión Génica , Mutación , Fenotipo , Supresión Genética , TóraxRESUMEN
Estrogens have been inextricably linked to the etiology of breast cancer. We have demonstrated that the female ACI rat exhibits a unique propensity to develop mammary cancers when treated continuously with physiological levels of 17 beta-estradiol (E2). The E2-induced mammary cancers are estrogen dependent and exhibit genomic instability. In contrast, the genetically related Copenhagen (COP) rat strain is relatively resistant to E2-induced mammary cancers. In this study we evaluated susceptibility to E2-induced mammary cancers in first filial (F(1)), second filial (F(2)), and backcross (BC) progeny generated from reciprocal intercrosses between the ACI and COP strains. F(1) progeny resembled the parental ACI strain with respect to incidence of E2-induced mammary cancers. However, latency was significantly prolonged in the F(1) populations. These data indicate that susceptibility behaves as an incompletely dominant phenotype in these crosses. Analysis of phenotypes exhibited by the F(1), F(2), and BC populations suggests that mammary cancer susceptibility is modified by one or two genetic loci in the reciprocal intercrosses between the ACI and COP strains. Susceptibility to E2-induced mammary cancers did not correlate with E2-induced pituitary growth in the genetically diverse F(2) and BC populations, suggesting that the genetic bases for susceptibility to E2-induced mammary cancers differ from those for E2-induced lactotroph hyperplasia.
Asunto(s)
Genes Dominantes , Predisposición Genética a la Enfermedad , Neoplasias Mamarias Experimentales/inducido químicamente , Neoplasias Mamarias Experimentales/genética , Animales , Cruzamientos Genéticos , Estradiol/farmacología , Femenino , Predisposición Genética a la Enfermedad/genética , Neoplasias Mamarias Experimentales/patología , Neoplasias Primarias Secundarias , Tamaño de los Órganos/efectos de los fármacos , Fenotipo , Hipófisis/patología , Ratas , Ratas Endogámicas ACI/genética , Ratas Endogámicas/genética , Factores de TiempoRESUMEN
BACKGROUND: We evaluated patient outcomes and complications associated with the microaxial Impella Recover left ventricular assist device (Impella Cardiosystems AG, Aachen, Germany) for postcardiotomy low-output syndrome. This low-cost device is inserted across the aortic valve through a 10-mm vascular graft sewn to the ascending aorta. METHODS: Impella patients were compared with 198 patients treated with an intraoperative intra-aortic balloon pump between January 2000 and December 2002. Three risk scores were used: the Hausmann score, the Texas Heart Institute score, and the Cleveland intensive care unit score. Between September 2001 and March 2003, 24 patients were treated with the Impella Recover for low-output syndrome. Before device insertion, 21 could not be separated from cardiopulmonary bypass, and 3 had postoperative hemodynamic instability despite high-dose catecholamines. Sixteen were treated with the Impella and intra-aortic balloon pump and 8 with the Impella alone (no intra-aortic balloon pump because of peripheral vascular disease or because deemed unnecessary). RESULTS: No technical problems with device insertion occurred. Pump flow was 3.3 +/- 0.7 L/min at 28,000 +/- 4500 RPM. Support time was 61 +/- 56 hours (range, 7-228 hours). Four devices required repositioning. One device failed (leaking purge line) and was removed. Hemolysis was minimal (lactate dehydrogenase levels of 540 +/- 260 U/dL for Impella survivors). Mortality for Impella patients was 54% (13/24), similar to that for high-risk intra-aortic balloon pump patients (Hausmann score > or =2 [57%], intensive care unit score > or =2 [51%], Texas Heart Institute score > or =0.75 [55%], and cardiac index < or =2.3 [45%]). Cardiac output data were available in 19 Impella patients. Impella patients able to increase their cardiac output to 1 L/min or more above the pump flow of the Impella Recover had a 10% (1/10) mortality, versus 88% (8/9) in patients with a residual cardiac function of 1 L/min or less (P =.001). Comparison of high-risk intra-aortic balloon pump patients with Impella patients with residual cardiac function of 1 L/min or more showed a significant reduction in mortality, regardless of the high-risk definition used. Residual cardiac function was the strongest predictor of survival in Impella patients. CONCLUSIONS: The Impella Recover device provides 3 to 4 L/min flow. It improves survival in patients with low-output syndrome if the heart is able to pump 1 L/min or more above device flow.
Asunto(s)
Gasto Cardíaco Bajo/terapia , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Corazón Auxiliar , Anciano , Gasto Cardíaco Bajo/etiología , Gasto Cardíaco Bajo/mortalidad , Diseño de Equipo , Femenino , Corazón Auxiliar/efectos adversos , Humanos , Contrapulsador Intraaórtico , Masculino , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
The electrical reactions of many central neurons depend on two voltage-activated K+ currents: the fast transient A-current IA and the delayed rectifier current IK. In rat dentate gyrus granule cells, the A-current density decreases during ontogenesis, possibly due to a redistribution of K+ channels from somata into dendrites. We tested this possibility in mechanically isolated granule cells with preserved dendrites of different length. Potassium currents were recorded with the whole-cell patch-clamp technique using prepulse protocols with and without a delay interval to isolate IA. A correlation between the length of the dendrites and the amount of A-current expressed in a given cell could not be demonstrated. Our findings therefore confirm an ontogenetic down regulation of A-currents.
Asunto(s)
Dendritas/fisiología , Regulación hacia Abajo/fisiología , Hipocampo/fisiología , Canales Iónicos/fisiología , Canales de Potasio/fisiología , Animales , Electrofisiología , Hipocampo/citología , Hipocampo/crecimiento & desarrollo , Técnicas In Vitro , Potenciales de la Membrana/fisiología , Tractos Piramidales/crecimiento & desarrollo , Tractos Piramidales/fisiología , RatasRESUMEN
The authors present the successful use of the Impella recover 100 intracardiac left ventricular assist device in a 55-year old man suffering from end-stage ischemic cardiomyopathy. The pump was implanted preoff pump coronary artery bypass grafting (OPCAB) and it was successfully weaned 5 days postoperatively. In addition, an intra-aortic balloon pump (IABP) was implanted to convert the non-pulsatile flow of the Impella into a pulsatile flow. In this paper benefits and risks of this technique are shown.
Asunto(s)
Cardiomiopatía Dilatada/complicaciones , Puente de Arteria Coronaria , Enfermedad Coronaria/cirugía , Corazón Auxiliar , Enfermedad Coronaria/complicaciones , Hemodinámica , Humanos , Contrapulsador Intraaórtico , Masculino , Persona de Mediana EdadRESUMEN
The organic solvent octane has been used routinely to permeabilize the hydrophobic vitelline membrane surrounding the Drosophila embryo, thereby allowing the movement of small molecules into the egg. We present evidence that hexane is a more effective permeabilizing agent than octane and compare the effects of these solvents on uniformity of permeabilization and embryonic viability. The ability of each solvent to make the embryo accessible to a range of biological stains was compared. The effect of octane versus hexane permeabilization on subsequent embryonic viability was measured at seven different stages during early embryogenesis. We found that although hexane is a superior solvent for permeabilizing the vitelline membrane, it decreases the viability of embryos exposed between 0 and 3 hr of age. Older embryos treated with either hexane or octane are usually viable. We also showed that molecules with a molecular mass of 984 Daltons or more did not diffuse into the embryo following treatment with either hexane or octane. Results presented here challenge a phase-partition model that has been proposed previously to explain the molecular basis of permeabilization of the Drosophila egg. An alternative model is described as well as an optimized protocol for permeabilizing and staining Drosophila embryos at any stage during early embryogenesis while maintaining viability for subsequent culture.
Asunto(s)
Drosophila/fisiología , Embrión no Mamífero/anatomía & histología , Animales , Colorantes , Hexanos , Histocitoquímica , Octanos , Solventes , Coloración y Etiquetado , Membrana Vitelina/efectos de los fármacos , Membrana Vitelina/metabolismoRESUMEN
HISTORY AND CLINICAL FINDINGS: A 23-year-old woman had received a mechanical bileaflet mitral valve prosthesis because of severe mitral valve insufficiency caused by an acute bacterial endocarditis with vegetations. One year after the operation the patient suffered on two miscarriages under oral anticoagulation by phenprocoumon. Present, she was referred to our center with the question of conversion to low molecular weight heparine because of continued yearning for a baby. INVESTIGATIONS: At admission the woman was in good general and nutritional condition. Echocardiography showed a regular prosthetic function. Blood analysis, electrolyte parameters and enzyme values were normal, further laboratory investigations revealed a factor-V-Leiden-mutation. A chromosomal analysis detected no aberrations. TREATMENT AND COURSE: The oral anticoagulation by phenprocoumon was switched to subcutaneous low molecular weight heparine in therapeutical dosage. Anti-factor-Xa-activity was controlled at regular intervals. Further pregnancy was uneventful for both, mother and child. A healthy infant was born by caesarean section at 40 (th) week of gestation. CONCLUSIONS: Treatment with anticoagulation by phenprocoumon is indispensable for mechanical heart valve protheses. Conversion to low molecular weight heparine is possible in patients who insistent request to conceive. The anticoagulation by low molecular weight heparine avoids teratogenic effects during pregnancy because the placenta is impermeable to that heparin. Furthermore, prophylaxis of thromoses by low molecular weight heparine is probably in almost the same manner as by phenprocoumon.
Asunto(s)
Anticoagulantes/uso terapéutico , Prótesis Valvulares Cardíacas , Heparina de Bajo-Peso-Molecular/uso terapéutico , Válvula Mitral , Complicaciones Cardiovasculares del Embarazo/tratamiento farmacológico , Trombosis/prevención & control , Anomalías Inducidas por Medicamentos/prevención & control , Aborto Espontáneo/inducido químicamente , Aborto Espontáneo/prevención & control , Anticoagulantes/efectos adversos , Endocarditis Bacteriana/complicaciones , Factor V/genética , Femenino , Heterocigoto , Humanos , Insuficiencia de la Válvula Mitral/etiología , Insuficiencia de la Válvula Mitral/cirugía , Fenprocumón/efectos adversos , Fenprocumón/uso terapéutico , Embarazo , Complicaciones Cardiovasculares del Embarazo/prevención & control , Trombosis/genética , Adulto JovenRESUMEN
The activating protein-1 (AP-1) transcription factor transduces growth signals through signal transduction pathways to the nucleus, leading to the expression of genes involved in growth and malignant transformation in many cell types. We have previously shown that overexpression of a dominant negative form of the cJun proto-oncogene, a cJun dominant negative mutant (Tam67), blocks AP-1 transcriptional activity, induces a G(1) cell cycle block and inhibits breast cancer cell growth in vitro and in vivo. We found that AP-1 blockade by Tam67 in MCF-7 breast cancer cells downregulates cyclin D1 transcriptional activity by at least two mechanisms: by suppressing transcription at the known AP-1 binding site (-934/-928) and by suppressing growth factor-induced expression through suppressing E2F activation at the E2F-responsive site (-726/-719). AP-1 blockade also led to reduced expression of E2F1 and E2F2, but not E2F4, at the mRNA and protein levels. Chromatin immunoprecipitation and supershift assays demonstrated that AP-1 blockade caused decreased binding of E2F1 protein to the E2F site in the cyclin D1 promoter. We also found that Tam67 suppressed the expression of the E2F1 dimerizing partner, DP1 and E2F-upregulated cell cycle genes (cyclins E, A, B and D3) and enhanced the expression of E2F-downregulated cell cycle genes (cyclins G(2) and I). Reduced expression of other E2F-regulated genes was also seen with AP-1 blockade and E2F suppression. Thus, the AP-1 factor regulates the expression of cyclin D and E2F (the latter in turn regulates E2F-downstream genes), leading to cell cycle progression and breast cancer cell proliferation.
Asunto(s)
Neoplasias de la Mama/patología , Ciclina D1/antagonistas & inhibidores , Factores de Transcripción E2F/metabolismo , Factor de Transcripción AP-1/metabolismo , Neoplasias de la Mama/genética , Línea Celular Tumoral , Proliferación Celular , Inmunoprecipitación de Cromatina , Ciclina D1/genética , Ciclina D1/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Regulación hacia Abajo , Factores de Transcripción E2F/genética , Factor de Transcripción E2F1/genética , Factor de Transcripción E2F1/metabolismo , Factor de Transcripción E2F2/genética , Factor de Transcripción E2F2/metabolismo , Factor de Transcripción E2F4/genética , Factor de Transcripción E2F4/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Fragmentos de Péptidos/metabolismo , Regiones Promotoras Genéticas , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-jun/metabolismo , ARN Mensajero/antagonistas & inhibidores , ARN Mensajero/metabolismo , Factor de Transcripción AP-1/antagonistas & inhibidores , Factor de Transcripción DP1/metabolismoRESUMEN
Coronary artery aneurysms and fistulae are very rare congenital anomalies. They occur in 0.2-0.4 % of all congenital heart diseases. In this article, we report a case of a four-year-old girl with a right coronary artery aneurysm and fistula draining into the right ventricle. Since the transcatheter coil embolization was not successful, surgical occlusion was considered in this case. We describe and discuss the handling of the fistula and the aneurysmatic enlargement of the proximal coronary artery.
Asunto(s)
Aneurisma Coronario/congénito , Aneurisma Coronario/terapia , Anomalías de los Vasos Coronarios/cirugía , Embolización Terapéutica/instrumentación , Fístula Vascular/congénito , Fístula Vascular/cirugía , Cateterismo Cardíaco , Preescolar , Aneurisma Coronario/diagnóstico , Angiografía Coronaria , Anomalías de los Vasos Coronarios/diagnóstico , Anomalías de los Vasos Coronarios/terapia , Ecocardiografía , Femenino , Ventrículos Cardíacos/anomalías , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Insuficiencia del Tratamiento , Resultado del Tratamiento , Fístula Vascular/diagnóstico , Fístula Vascular/fisiopatología , Fístula Vascular/terapiaRESUMEN
Nitric oxide (NO) and calcitonin gene-related peptide (CGRP), potent vasodilators in the meninges,may be involved in the pathophysiology of vascular headaches such as migraine pain. NO donators can provoke headache attacks in migraineurs and increased levels of CGRP have been found in the venous outflow from the head during migraine attacks. We therefore examined the effect of both NO and CGRP on dural blood, a process which may parallel nociceptive processes in the meninges. 1. Arterial blood flow was measured in the exposed dura mater encephali of the rat using laser Doppler flowmetry. Local application of different NO donors (SNAP,NONOate, and NOC-12) caused dose-dependent increases in meningeal blood flow. CGRP(8-37) at 10(-4) M did not significantly change the basal flow but attenuated increases in blood flow caused by the NO donors at concentrations of 10(-5)-10(-3) M.2. In another series of experiments, the hemisected skulls of adult Wistar rats, complete with intact dura mater, were filled with oxygenated synthetic interstitial fluid (SIF) and the CGRP content of this fluid was assessed every 5 min. When the NO donator NONOate, at concentrations of 10(-5)-10(-3) M, was added to the SIF, or when the SIF was bubbled with NO gas (1000 ppm in N(2) atmosphere) instead of carbogen, CGRP release increased in a concentration-dependent manner. We conclude that the vasodilatory effect of NO that causes increased meningeal blood flow is in part the result of both stimulating the release of CGRP and promoting the vasodilatory action of CGRP. Since NO donors such as nitroglycerin are known to provoke headache and CGRP is released during migraine pain, the NO-stimulated CGRP release may be relevant for the development of vascular headaches that are accompanied by meningeal hyperaemia.
Asunto(s)
Duramadre/metabolismo , Cefalea/fisiopatología , Neuropéptidos/metabolismo , Donantes de Óxido Nítrico/farmacología , Óxido Nítrico/farmacología , Animales , Péptido Relacionado con Gen de Calcitonina/farmacología , Duramadre/irrigación sanguínea , Duramadre/efectos de los fármacos , Flujometría por Láser-Doppler , Compuestos Nitrosos/farmacología , Ratas , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/fisiología , S-Nitroso-N-Acetilpenicilamina/farmacologíaRESUMEN
Research was undertaken to test the hypothesis that thalidomide-induced limb defects resulted from damage to the neural crest or peripheral nerves and that normal limb development depends upon either the quality (level specific) or quantity of peripheral nerves. Barriers which were placed into early chick embryos to block brachial plexus-level neural crest cells from reaching the limb resulted in normal limb skeletons. These data agree with previous work in suggesting that skeletal morphology is independent of innervation.
Asunto(s)
Huesos/embriología , Extremidades/inervación , Nervios Periféricos/fisiología , Alas de Animales/inervación , Animales , Embrión de Pollo , Pollos , Extremidades/embriología , Extremidades/patología , Especificidad de la Especie , Alas de Animales/embriologíaRESUMEN
This study addresses possible interactions of the vasodilators nitric oxide (NO), calcitonin gene-related peptide (CGRP) and prostaglandins, which may be implicated in the generation of vascular headaches. Local application of the NO donator diethylamine-NONOate (NONOate) to the exposed dura mater encephali of the rat caused dose-dependent increases in meningeal blood flow recorded by laser Doppler flowmetry. Pre-application of the CGRP receptor antagonist CGRP8-37 significantly attenuated the evoked blood flow increases, while the cyclooxygenase inhibitors acetylsalicylic acid and metamizol were only marginally effective. Stimulation of rat dura mater with NONOate in vitro caused increases in CGRP release. NADPH-diaphorase activity indicating NO production was restricted to the endothelium of dural arterial vessels. We conclude that increases in meningeal blood flow caused by NO depend partly on the release and vasodilatory action of CGRP from dural afferents, while prostaglandins are not significantly involved.
Asunto(s)
Circulación Cerebrovascular/fisiología , Meninges/irrigación sanguínea , Meninges/metabolismo , Óxido Nítrico/biosíntesis , Antagonistas de Prostaglandina/farmacología , Prostaglandinas/biosíntesis , Receptores de Péptido Relacionado con el Gen de Calcitonina/metabolismo , Animales , Dinoprostona/metabolismo , Relación Dosis-Respuesta a Droga , Duramadre/enzimología , Hidrazinas/farmacología , Masculino , Meninges/efectos de los fármacos , Meninges/enzimología , NADPH Deshidrogenasa/metabolismo , Óxido Nítrico/fisiología , Donantes de Óxido Nítrico/farmacología , Óxidos de Nitrógeno , Prostaglandinas/metabolismo , Ratas , Ratas Wistar , Receptores de Péptido Relacionado con el Gen de Calcitonina/fisiologíaRESUMEN
A number of hypotheses have been presented to explain the mechanism of action of thalidomide. The most widely published and apparently widely accepted hypothesis is that of embryonic neuropathy advanced by McCredie and McBride. This paper reviews the points of the hypothesis and analyzes it in light of known limb embryology supported with recent experimental evidence which directly tests the hypothesis. The hypothesis may be considered as being composed of two separate parts. The first part proposes that thalidomide-induced limb defects exhibit a segmental pattern. The second proposes that the segmental pattern of limb defects is a result of segmental peripheral neuropathy. We are in complete agreement with the first portion of the hypothesis, but find the second portion quite unlikely.
Asunto(s)
Deformidades Congénitas de las Extremidades , Cresta Neural/efectos de los fármacos , Nervios Periféricos/efectos de los fármacos , Talidomida/efectos adversos , Animales , Huesos/efectos de los fármacos , Embrión de Pollo , Niño , Extremidades/embriología , Extremidades/inervación , Humanos , Nervios Periféricos/embriologíaRESUMEN
The value of exercise ECG in predicting the occurrence of restenosis after successful transluminal coronary angioplasty (PTCA) was investigated in 398 patients with exercise tests of comparable workload before, immediately after and within 6 months after PTCA. In patients with normalized exercise ECG (n = 166) restenosis was observed in 16.3% and indication for repeat PTCA was present in 6.6%. RePTCA was recommended in only 3.2% of patients if the exercise test was still normal at restudy and if the patients were free of anginal symptoms. In patients with a renewed ST-segment depression (n = 77) the rate of restenosis was 67.5% and the indication for rePTCA was present in 52%. In patients without changes in the exercise tests before and after PTCA and at restudy (n = 155) restenosis was seen in 25.8% and rePTCA was recommended in 14.2%. It is concluded that from the clinical point of view, in patients with improved exercise ECG at restudy, especially if they are free of angina, there is no need for a re-angiogram because indications for rePTCA are very rare.
Asunto(s)
Angioplastia Coronaria con Balón , Angiografía Coronaria , Enfermedad Coronaria/terapia , Electrocardiografía , Prueba de Esfuerzo , Enfermedad Coronaria/diagnóstico , Femenino , Estudios de Seguimiento , Masculino , RecurrenciaRESUMEN
We have used hypomorphic and null tailless (tll) alleles to carry out a detailed analysis of the effects of the lack of tll gene activity on anterior and posterior regions of the embryo. The arrangement of tll alleles into a continuous series clarifies the relationship between the anterior and posterior functions of the tll gene and indicates that there is a graded sensitivity of anterior and posterior structures to a decrease in tll gene activity. With the deletion of both anterior and posterior pattern domains in tll null embryos, there is a poleward expansion of the remaining pattern. Using anti-horseradish peroxidase staining, we show that the formation of the embryonic brain requires tll. A phenotypic and genetic study of other pattern mutants places the tll gene within the hierarchy of maternal and zygotic genes required for the formation of the normal body pattern. Analysis of mutants doubly deficient in tll and maternal terminal genes is consistent with the idea that these genes act together in a common pathway to establish the domains at opposite ends of the embryo. We propose that tll establishes anterior and posterior subdomains (acron and tail regions, respectively) within the larger pattern regions affected by the maternal terminal genes.
Asunto(s)
Drosophila/embriología , Genes , Cigoto/fisiología , Alelos , Animales , Encéfalo , Mapeo Cromosómico , Drosophila/genética , Mutación , Fenotipo , Cola (estructura animal)RESUMEN
Cell fates in the anterior and posterior termini of the Drosophila embryo are programmed by multiple zygotic genes that are regulated in response to a maternally encoded signal transduction pathway. These genes specify terminal as distinct from central cell fates, program pattern along the anteroposterior and dorsoventral axes of the termini, and also control endoderm specification and terminal morphogenetic movements. Here, we use a genetic interaction test to dissect the zygotic components of the terminal genetic hierarchy. We show that two genes, lines and empty spiracles, act downstream of tailless to repress central and promote terminal cell fates along the anteroposterior axis of the termini. Genes that control dorsoventral pattern in the termini and genes that program terminal morphogenesis act in distinct branches of the genetic hierarchy that are independent of tailless.
Asunto(s)
Blastodermo/fisiología , Drosophila/embriología , Drosophila/genética , Mutación , Alelos , Animales , Blastodermo/citología , Embrión no Mamífero/citología , Embrión no Mamífero/fisiología , Morfogénesis , FenotipoRESUMEN
The developmental signal that specifies the fates of cells at the anterior and posterior termini of the Drosophila embryo is transmitted by the torso receptor tyrosine kinase. This paper presents the results of a genetic interaction test for zygotic loci that act downstream of torso in the terminal genetic hierarchy. Tests of 26 zygotic mutants with defects in terminal development indicate that at least 14 reside in this hierarchy. The phenotypes associated with these genes fall into three classes, each of which represents a distinct aspect of terminal development and evolution. Four of the genes have been molecularly cloned and their products include an intercellular communication factor and three kinds of transcription factors.
Asunto(s)
Drosophila melanogaster/embriología , Proteínas Tirosina Quinasas/fisiología , Animales , Diferenciación Celular , Drosophila melanogaster/enzimología , Drosophila melanogaster/genética , Expresión Génica , Genes , Morfogénesis , Fenotipo , CigotoRESUMEN
The recessive zygotic lethal mutation tailless maps to region 100A5,6-B1,2 at the tip of the right arm of chromosome 3, and results in shortened pharyngeal ridges in the head skeleton of the mature embryo and the elimination of the eighth abdominal segment and telson. Although they have a normal body length, tailless embryos have a smaller number of abdominal segments, some of which are larger than normal. The mutant phenotype is seen as early as 8 hr postfertilization, when tailless embryos are observed to have fewer tracheal pits than wildtype. At 9 hr, tailless embryos appear to be missing segments A8, A9, and A10 and have an abnormal clypeolabrum, optic lobes, and procephalic lobe. Segments A4, A5, A6, and A7 appear larger in tailless embryos than wildtype at this stage. The tailless mutation, although affecting anterior and posterior ectodermal structures in the mature embryo, does not affect the formation of pole cells, the posterior midgut, or the proctodeum, which arise from the most posterior region of the embryo. The mutation does result, however, in the failure of Malpighian tubule formation. Consistent with its effect on ectodermal segments, tailless leads to a reduction in the number of segmented, paired ganglia in the ventral nerve cord as well as to an abrupt alteration in the posterior region of the tracheal system. The role the tailless gene may play in the formation of the most anterior and posterior regions of the embryo's ectodermal body plan is discussed.
Asunto(s)
Drosophila melanogaster/embriología , Ectodermo/fisiología , Cigoto/fisiología , Acetilcolinesterasa/metabolismo , Animales , Escarabajos/embriología , Drosophila melanogaster/genética , Embrión no Mamífero/fisiología , Endodermo/fisiología , Gástrula/fisiología , Microscopía Electrónica de Rastreo , Mutación , Sistema Nervioso/embriologíaRESUMEN
Dilated lateral cerebral ventricles have been reported in association with psychiatric disorders. The dilatation is likely secondary to changes in anatomically related centers in the brain. Our attention is focused on the caudate nucleus and the need to develop quantitative characterization of it in psychiatric research. A computer method is described for accurately detecting the edges of the caudate nuclei in CT scans. The method consists of a two-dimensional filtering step to reduce image noise, followed by gradient computation for edge enhancement, and then an edge detection step to identify and record the caudate nuclei cross sections. Results from both head scans and synthetic images indicate that the method is successful even for low-contrast edges where the standard deviation of image noise approaches the difference in mean HU across the edge. The availability of an automated method of delineating the caudate nucleus permits the cross-sectional area and shape to be determined, the density to be estimated, and, from a set of closely spaced slices, volume information to be obtained.