RESUMO
Most of the 131 cells that die during the development of a Caenorhabditis elegans hermaphrodite do so approximately 30 min after being generated. Furthermore, in these cells, the pro-caspase proCED-3 is inherited from progenitors and the transcriptional upregulation of the BH3-only gene egl-1 is thought to be sufficient for apoptosis induction. In contrast, the four CEM neurons, which die in hermaphrodites, but not males, die approximately 150 min after being generated. We found that in the CEMs, the transcriptional activation of both the egl-1 and ced-3 gene is necessary for apoptosis induction. In addition, we show that the Bar homeodomain transcription factor CEH-30 represses egl-1 and ced-3 transcription in the CEMs, thereby permitting their survival. Furthermore, we identified three genes, unc-86, lrs-1, and unc-132, which encode a POU homeodomain transcription factor, a leucyl-tRNA synthetase, and a novel protein with limited sequence similarity to the mammalian proto-oncoprotein and kinase PIM-1, respectively, that promote the expression of the ceh-30 gene in the CEMs. On the basis of these results, we propose that egl-1 and ced-3 transcription are coregulated in the CEMs to compensate for limiting proCED-3 levels, which most probably are a result of proCED-3 turn over. Similar coregulatory mechanisms for BH3-only proteins and pro-caspases may function in higher organisms to allow efficient apoptosis induction. Finally, we present evidence that the timing of the death of the CEMs is controlled by TRA-1 Gli, the terminal global regulator of somatic sexual fate in C. elegans.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Caspases/metabolismo , Neurônios/metabolismo , Proteínas Repressoras/metabolismo , Ativação Transcricional , Sequência de Aminoácidos , Animais , Apoptose , Proteínas de Caenorhabditis elegans/genética , Caspases/genética , Genótipo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Masculino , Dados de Sequência Molecular , Fatores do Domínio POU/genética , Fatores do Domínio POU/metabolismo , Proteínas Repressoras/genética , Regulação para CimaRESUMO
We have solved the crystal structure of aphrodisin, a pheromonal protein inducing a copulatory behaviour in male hamster, using MAD methods with selenium, at 1.63 A resolution. The monomeric protein belongs to the lipocalin family, and possesses a disulfide bridge in a loop between strands 2 and 3. This disulfide bridge is characteristic of a family of lipocalins mainly identified in rodents, and is analogous to the fifth disulfide bridge of the long neurotoxins, such as alpha cobratoxin. An elongated electron density was found inside the buried cavity, which might represent a serendipitous ligand of unknown origin. The analysis of the water accessible surfaces of the side-chains bordering the cavity indicates that Phe76 may be the door for the natural ligand to access the cavity. This residue defines the entry of the cavity as belonging to the consensus for lipocalins. The face bearing Phe76 might also serve for the interaction with the receptor.
Assuntos
Feromônios/química , Proteínas/química , Sequência de Aminoácidos , Animais , Sítios de Ligação , Proteínas de Transporte/química , Proteínas Neurotóxicas de Elapídeos/química , Sequência Consenso , Cricetinae , Cristalografia por Raios X , Dissulfetos/química , Dissulfetos/metabolismo , Feminino , Glicosilação , Ligantes , Lipocalina 1 , Modelos Moleculares , Dados de Sequência Molecular , Fenilalanina/metabolismo , Feromônios/metabolismo , Estrutura Secundária de Proteína , Proteínas/metabolismo , Selênio/metabolismo , Alinhamento de Sequência , Água/metabolismoRESUMO
Natural populations of fruit flies of the Bactrocera dorsalis complex exhibit chromosomal variation based on differences in the amount and distribution of constitutive heterochromatin in the centromeric regions of the autosomes and the sex chromosomes. The chromosomal variation, coupled with differences in external morphology and host plant specific preferences, strongly suggest the existence of 5 closely related species within the B. dorsalis complex that have provisionally been designated B. dorsalis species B, C, D, and E in contrast with B. dorsalis s.s. (species A). Analysis of heterochromatin in autosomes and sex chromosomes has revealed 4 distinct groups of mitotic karyotypes. Bactrocera dorsalis is the only representative of Group I, which is characterized by the typical metacentric X chromosome and major blocks of centromeric heterochromatin in autosomes 5 and 6. Group 2 consists of species B and C, which show prominent landmarks of pericentric heterochromatin in all autosomes and in the X chromosome. Group 3 comprises species D, which is characterized by conspicuous blocks of pericentric heterochromatin in all autosomes but the long arm of the subtelocentric X chromosome is euchromatic and lacks a major portion of centromeric heterochromatin. Species E belongs to Group 4, which differs from Group 3 in having major blocks of heterochromatin at the distal portion of the X chromosome in addition to the prominent landmarks of pericentric heterochromatin in all autosomes. Chromosomal evolution among closely related species within the B. dorsalis complex clearly involves the presence or absence of constitutive heterochromatin in the centromeric regions of autosomes as well as in the X chromosome.
Assuntos
Drosophila/genética , Metáfase , Animais , Bandeamento Cromossômico , Feminino , Cariotipagem , MasculinoRESUMO
In 9 cases of buphthalmos 'in vivo-measurements of the latitude of Schlemm's canal gave us a mean value of 678 micron. The extreme values ranged between 600 micron and 800 micron. Therefore these values differ significantly from those measured 'in vivo' in chronic simple glaucoma (x:542 micron, extreme values 425 micron and 625 micron). The latitude of Schlemm's canal correlates with the diameter of cornea and the rise of intra-oculare pressure. In cases of buphtha-mos the success of trabeculotomy seems to be better, if the latitude of Schlemm's canal is less than l50 micron. Trabeculotomy should therefore be performed as soon as possible.
Assuntos
Córnea/anatomia & histologia , Hidroftalmia/fisiopatologia , Esclera/anatomia & histologia , Doença Crônica , Glaucoma/fisiopatologia , Humanos , Hidroftalmia/cirurgia , Pressão Intraocular , Malha Trabecular/cirurgiaRESUMO
Following trabeculotomy, about 30% of glaucomatous eyes are not normalized in pressure without additional therapy. In these cases, it was not possible to remove the resistance of outflow completely. Before deciding to perform trabeculotomy it is, therefore, necessary to localize the resistance of outflow. The inspection of the blood pattern in Schlemm's canal gives no indication where to localize the resistance of outflow. The same holds true for the haemorrhage deriving from Schlemm's canal, in the operating field (trabeculotomy window), which appears in 19.2% of cases. After trabeculotomy the blood outflow into the anterior chamber is significantly higher (63.6%) using the suction cup, then following pressure of the gonioscopy lens (28.1%). The differences between these findings are discussed. Our results indicate the necessity to search for other methods in localizing the resistance of outflow pre-operatively.
Assuntos
Humor Aquoso/fisiologia , Glaucoma/cirurgia , Pressão Intraocular , Humanos , Esclera/irrigação sanguínea , Esclera/cirurgia , Malha Trabecular/cirurgiaRESUMO
Iontophoresis is less apt to prove the existence of outflow channels of aqueous humour, but it is appropriate in demonstrating filtering blebs. After injecting fluorescein directly into the anterior chamber, the outflow channels are clearly marked in enucleated non-glaucomatous eyes, as well as in eyes containing a tumor, prior to enucleation. Regularly, one is able to observe sectors in which the aqueous veins are filled slowly or not filled at all. Injecting fluorescein directly in Schlemm's canal proves that in cadaver eyes without glaucoma the lumen is open all around. Sectorial filling defects of vessels leading out of Schlemm's canal are often seen. In three patients with simple glaucoma blocking of dye was noticed during passage through Schlemm's canal without reappearance. Our experiments give the impression that segmental division of Schlemm's canal is more marked in eyes with glaucoma than in normal eyes. If local occlusions within Schlemm's canal are of importance for the range of lowering of intraocular pressure, one must differentiate between the trabecular and the intrascleral part of the resistance of outflow in the operation field, in order to choose the best operating procedure. Such a differentiation seems, in principle, possible using fluorescein--primarily injected into the anterior chamber directly, and secondarily into a given part of Schlemm's canal.
Assuntos
Humor Aquoso/fisiologia , Glaucoma/cirurgia , Pressão Intraocular , Câmara Anterior , Fluoresceínas/administração & dosagem , Glaucoma/fisiopatologia , Humanos , Iontoforese , Esclera/cirurgia , Malha Trabecular/cirurgiaRESUMO
The possibility of complications connected with trabeculotomy led us to the development of the so-called hook probe. Instead of being twisted into the anterior chamber the probe is successively pulled back into Schlemm's canal, thereby tearing the trabecular meshwork. Complications connected with the turning of the probe can thus be avoided. Three techniques of trabeculotomy are compared: Harms trabeculotomy, with the turning of the probe over 60 degrees or 120 degrees and trabeculotomy with the hook probe over 60 degrees of the circumference. This use of the hook probe results in minimal trauma to the anterior part of the eye. Hemorrhaging particularly is infrequent or often even absent, during the cutting of the trabecular meshwork. The influence on intraocular pressure does not significantly differ between use of the hook probe and use of Harms probe. The dependence of intraocular pressure on length of tearing distance could not be determined. The results give the impression that a portion of the outflow resistance-at least postoperatively-within a greater percentage of simple glaucoma eyes lies distally to the trabecular meshwork. In choosing the best technique for operating, it is therefore important to know whether the outflow resistance in each individual case is mainly localized trabecularly or intrascleraly.
Assuntos
Glaucoma/cirurgia , Instrumentos Cirúrgicos , Malha Trabecular/cirurgia , Seguimentos , Hemorragia/prevenção & controle , Humanos , Pressão Intraocular , Complicações Pós-OperatóriasRESUMO
A transtrabecular iridectomy was performed in 17 eyes with narrow angle glaucoma, and in 3 eyes in which the trabecular meshwork was gonioscopically not visible. Postoperatively, the conjunctive lied directly on the sclera in 14 cases; in 6 cases a circumscribed conjunctival bleb developed in the operation field. After a follow-up of 12 or 24 months, the intraocular pressure was normalized without miotics in 15 of 17 eyes. The mechanism of transtrabecular iridectomy is discussed.
Assuntos
Glaucoma/cirurgia , Iris/cirurgia , Seguimentos , Humanos , Pressão Intraocular , Malha Trabecular/cirurgiaRESUMO
We tried to modify the technique of trabeculotomy in order to minimize the trauma to the anterior part of the eye, when tearing the trabecular meshwork. (1) With help of an annular probe, having a lumen, a nylon thread is pushed through Schlemm's canal and the trabecular meshwork cutted circumferentially. (2) With a 'flat probe', corresponding to the configuration of Schlemm's canal, the trabecular meshwork is torn. (3) A so-called 'hook probe' is described, which tears the trabecular meshwork while being sucessively pulled backwards. According to our experiments, the usefulness of the thread technique and of the 'flat probe' is not yet to be decided upon. On the other hand, the advantages of the 'hook probe' are clearly visible, in avoiding the complications connected with twisting the probe into the anterior chamber.
Assuntos
Glaucoma/cirurgia , Malha Trabecular/cirurgia , Humanos , Métodos , Complicações Pós-Operatórias/prevenção & controle , Sucção/instrumentaçãoAssuntos
Corpo Ciliar/cirurgia , Cauterização , Glaucoma/cirurgia , Humanos , Pressão Intraocular , MétodosRESUMO
"In vivo" measurements of lumen of Schlemm's canal were performed on 38 eyes with trabeculotomy made for chronic simple glaucoma. The mean value of lumen was 542 mum, much higher than the mean values measured on cadavers and quoted in literature. Contraction due to fixation and dehydration may be the main cause of those differences.
Assuntos
Corpo Ciliar , Glaucoma , Esclera , Doença Crônica , HumanosRESUMO
The lumen of Schlemm's canal increases "in vivo" and in experiments on cadaver eyes, with the increase of intra-ocular pressure. It is accepted that the trabecular structures are extended with the raise of inra-ocular pressure. The relation of "in vivo" measurements of the canal with the intra-ocular pressure does not allow any conclusions to be drawn about localisation of outflow obstructions. The viriations of the obtained values is an expression of structural differences in the canal lumen.
Assuntos
Corpo Ciliar , Glaucoma , Pressão Intraocular , Esclera , Glaucoma/patologia , Humanos , Esclera/patologiaRESUMO
A new surgical technique in the treatment of chronic narrow-angle glaucoma is described. After forming a scleral flap and opening of Schlemm's canal a probe is inserted into the canal. We dissect the sclera and the outer wall of Schlemm's canal by an oblique cut. The probe being retracted again, the trabecular meshwork is cut and a basal iridectomy is performed. Then the scleral cut and the trabecular window are closed tightly. Postoperative pressure behaviour and gonioscopy indicate, that the outflow of aqueous humour occurs via trabecular cleft and the collector channels in the operating field; obviously with this technique the intrascleral outflow channels can be saved to a great extend.
Assuntos
Glaucoma/cirurgia , Iris/cirurgia , Doença Crônica , Córnea/cirurgia , Gonioscopia , Humanos , Pressão Intraocular , Métodos , Complicações Pós-Operatórias , Esclera/cirurgiaRESUMO
Report on seven patients with giantcell arteritis. An ophthalmodynamographic finding typical for these aspects of case was recorded in all cases. In one-sided and permanently one-sided functional disturbances, too, a pathologically reduced pulsation volume on both sides could always be derived.
Assuntos
Arterite de Células Gigantes/diagnóstico , Oftalmodinamometria , Cegueira/etiologia , Arterite de Células Gigantes/complicações , Cefaleia/diagnóstico , Cefaleia/etiologia , Humanos , Testes de Campo VisualRESUMO
In infants without glaucoma measurements of the intraocular pressure were performed with the Draeger tonometer and the Schiotz tonometer. Our measurements indicate, that by use of the applanation tonometer the results are more reliable. The average intraocular pressure readings were 10.68 plus or minus 6.0 mm Hg (x plus or minus 2 s).