THE retina in birds projects to the contralateral tectum. Our previous study and some otherphysiological, histochetnical and neurochemical evidence have suggested that the retino-tectal projection in birds might use g...THE retina in birds projects to the contralateral tectum. Our previous study and some otherphysiological, histochetnical and neurochemical evidence have suggested that the retino-tectal projection in birds might use glutamate as an excitatory transmitter. However, very lit-tle is known about its particular receptor type(s), because there are at least three major phar-macologically defined types of glutamate receptors: NMDA, AMPA/Kainate, andmetabotropic glutamate receptors.展开更多
For the first time we have shown here that the constituent from tectal extract (Te) which can support and promote the survival and growth of the retinal ganglion cell is a 30 kD protein. (i) Using MTT colorimetric mic...For the first time we have shown here that the constituent from tectal extract (Te) which can support and promote the survival and growth of the retinal ganglion cell is a 30 kD protein. (i) Using MTT colorimetric microassay to measure the optical density for the survival and growth of the cultured retinal neuron, it was found that the optical densities for the experimental cultures with either Te, or its 10-30 kD fraction, or its ≥30 kD fraction were 2-4 times that of the control culture without Te (P【0.01). This indicated that experimental cultures were more active in growth, (ii) The retinal neurons cultured on Te Phast gels showed that large retinal neurons (】18 μm) grew only on the gel region containing the 30 kD protein. The retrograde prelabelled with horseradish peroxidase (HRP) for retinal ganglion cells indicated that these surviving neurons grown on Te Phast gel were HRP positive, i.e. retinal ganglion cells, (iii) The retinal explants cultured with 30 kD gels at a close distance of 1 mm展开更多
Investigating the cellular and molecular mechanisms involved in the development of topographically ordered connections in the central nervous system constitutes an important issue in neurobiology because these connect...Investigating the cellular and molecular mechanisms involved in the development of topographically ordered connections in the central nervous system constitutes an important issue in neurobiology because these connections are the base of the central nervous system normal function.The dominant model to study the development of topographic maps is the projection from the retinal ganglion cells to the optic tectum/colliculus.The expression pattern of Eph/ephrin system in opposing gradients both in the retina and the tectum,labels the local addresses on the target and gives specific sensitivities to growth cones according to their topographic origin in the retina.The rigid precision of normal retinotopic mapping has prompted the chemoaffinity hypothesis,positing axonal targeting to be based on fixed biochemical affinities between fibers and targets.However,several lines of evidence have shown that the mapping can adjust to experimentally modified targets with flexibility,demonstrating the robustness of the guidance process.Here we discuss the complex ways the Ephs and ephrins interact allowing to understand how the retinotectal mapping is a precise but also a flexible process.展开更多
Antineoplastons A10 and AS2-1 (ANP) are synthetic derivatives of glutamine, isoglutamine, and phenylacetic acid. In 1993, a phase II clinical trial program began according to protocols based on the initial protocol, B...Antineoplastons A10 and AS2-1 (ANP) are synthetic derivatives of glutamine, isoglutamine, and phenylacetic acid. In 1993, a phase II clinical trial program began according to protocols based on the initial protocol, BT-06, which was transferred from the National Institutes of Health (NIH). Protocol BT-09 was designed for different types of primary brain tumors in adults that were not curable by standard treatment. The study was designed as a single arm, two-stage, phase II trial of ANP as a monotherapy in a high-risk, poor-prognosis population. The total number of registered subjects was 40. The majority of patients were diagnosed with high-grade tumors (N = 33). In this group, 12 patients carried diagnosis of anaplastic astrocytoma (AA) and 11 patients of glioblastoma. In the group of low-grade tumors (N = 7), there were 6 cases of low-grade glioma, and 1 neurocytoma grade 2. A group of 12 patients did not receive any prior treatment, 12 patients had surgical resection only, 5 patients received radiation therapy (RT) only, and 11 patients received both RT and chemotherapy. The median duration of ANP was 16.6 weeks. The median dosage of A10 was 7.16 g/kg/d and AS2-1 was 0.27 g/kg/d. Responses were accessed by gadolinium-enhanced magnetic resonance imaging (MRI). Objective responses (OR) in all patients were 22.5% and in the AA group were 41.7% of patients. The median progression-free survival (PFS) in the AA group was 5.4 months. The median overall survival (OS) was 12.7 months and OS at 1 and 2 years was 54.5% and 45.5% correspondingly. The treatment was well-tolerated with reversible grade 3 and 4 toxicities in 35% of all patients (N = 40). In conclusion, the study reached efficacy endpoint and ANP was well-tolerated and compared favorably to the current treatment of AA.展开更多
文摘THE retina in birds projects to the contralateral tectum. Our previous study and some otherphysiological, histochetnical and neurochemical evidence have suggested that the retino-tectal projection in birds might use glutamate as an excitatory transmitter. However, very lit-tle is known about its particular receptor type(s), because there are at least three major phar-macologically defined types of glutamate receptors: NMDA, AMPA/Kainate, andmetabotropic glutamate receptors.
基金This research is supported by research grants from the Croucher Foundation, the University of Hong Kong, Medical Research Grant Fund, and the UPGC grant 221400030.
文摘For the first time we have shown here that the constituent from tectal extract (Te) which can support and promote the survival and growth of the retinal ganglion cell is a 30 kD protein. (i) Using MTT colorimetric microassay to measure the optical density for the survival and growth of the cultured retinal neuron, it was found that the optical densities for the experimental cultures with either Te, or its 10-30 kD fraction, or its ≥30 kD fraction were 2-4 times that of the control culture without Te (P【0.01). This indicated that experimental cultures were more active in growth, (ii) The retinal neurons cultured on Te Phast gels showed that large retinal neurons (】18 μm) grew only on the gel region containing the 30 kD protein. The retrograde prelabelled with horseradish peroxidase (HRP) for retinal ganglion cells indicated that these surviving neurons grown on Te Phast gel were HRP positive, i.e. retinal ganglion cells, (iii) The retinal explants cultured with 30 kD gels at a close distance of 1 mm
基金supported by Consejo Nacional de Investigaciones Científicas y Técnicas(PIP 00441)Universidad de Buenos Aires(M 00526BA,00769BA,both to GS)
文摘Investigating the cellular and molecular mechanisms involved in the development of topographically ordered connections in the central nervous system constitutes an important issue in neurobiology because these connections are the base of the central nervous system normal function.The dominant model to study the development of topographic maps is the projection from the retinal ganglion cells to the optic tectum/colliculus.The expression pattern of Eph/ephrin system in opposing gradients both in the retina and the tectum,labels the local addresses on the target and gives specific sensitivities to growth cones according to their topographic origin in the retina.The rigid precision of normal retinotopic mapping has prompted the chemoaffinity hypothesis,positing axonal targeting to be based on fixed biochemical affinities between fibers and targets.However,several lines of evidence have shown that the mapping can adjust to experimentally modified targets with flexibility,demonstrating the robustness of the guidance process.Here we discuss the complex ways the Ephs and ephrins interact allowing to understand how the retinotectal mapping is a precise but also a flexible process.
文摘Antineoplastons A10 and AS2-1 (ANP) are synthetic derivatives of glutamine, isoglutamine, and phenylacetic acid. In 1993, a phase II clinical trial program began according to protocols based on the initial protocol, BT-06, which was transferred from the National Institutes of Health (NIH). Protocol BT-09 was designed for different types of primary brain tumors in adults that were not curable by standard treatment. The study was designed as a single arm, two-stage, phase II trial of ANP as a monotherapy in a high-risk, poor-prognosis population. The total number of registered subjects was 40. The majority of patients were diagnosed with high-grade tumors (N = 33). In this group, 12 patients carried diagnosis of anaplastic astrocytoma (AA) and 11 patients of glioblastoma. In the group of low-grade tumors (N = 7), there were 6 cases of low-grade glioma, and 1 neurocytoma grade 2. A group of 12 patients did not receive any prior treatment, 12 patients had surgical resection only, 5 patients received radiation therapy (RT) only, and 11 patients received both RT and chemotherapy. The median duration of ANP was 16.6 weeks. The median dosage of A10 was 7.16 g/kg/d and AS2-1 was 0.27 g/kg/d. Responses were accessed by gadolinium-enhanced magnetic resonance imaging (MRI). Objective responses (OR) in all patients were 22.5% and in the AA group were 41.7% of patients. The median progression-free survival (PFS) in the AA group was 5.4 months. The median overall survival (OS) was 12.7 months and OS at 1 and 2 years was 54.5% and 45.5% correspondingly. The treatment was well-tolerated with reversible grade 3 and 4 toxicities in 35% of all patients (N = 40). In conclusion, the study reached efficacy endpoint and ANP was well-tolerated and compared favorably to the current treatment of AA.