2-Amino-5-phosphonovalerate and Co2+ selectively block depolarization and burst firing of rat hippocampal CA1 pyramidal neurones by N-methyl-D-aspartate

Intracellular recordings from pyramidal neurones during microiontophoretic ejection of N-methyl-D-aspartate and quisqualate into the pyramidal cell layer of the CA1 region of the rat hippocampal slice showed that both amino acids caused depolarization and evoked spike activity. Whereas quisqualate evoked tetrodotoxin-sensitive spikes, those produced by N-methyl-D-aspartate consisted of bursts of tetrodotoxin-sensitive action potentials superimposed on an underlying depolarizing shift of membrane potential. Both membrane depolarization and the superimposed depolarizing shifts associated with N-methyl-D-aspartate excitation were selectively and reversibly antagonized by the D(-) isomer of 2-amino-5-phosphonovalerate and Co2+. Both amino acids caused an increase in membrane conductance when small ejection currents were used, and the depolarizing response to these compounds was prevented by current injection. However, only the increase by N-methyl-D-aspartate was blocked by 2-amino-5-phosphonovalerate and Co2+. These results provide evidence to support the suggestion that different mechanisms underlie the excitatory response to N-methyl-D-aspartate and quisqualate in CA1 pyramidal neurones.     

Exploration of the volumetric composition of human lung cancer nodules in correlated histopathology and computed tomography

Gaining a complete and comprehensive understanding of lung cancer nodule histological compositions and how these tissues are represented in radiological data is important not only for expanding the current knowledge base of cancer growth and development but also has potential implications for classification standards, radiological diagnosis methods and for the evaluation of treatment response. In this study we generate large scale histological segmentations of the cancerous and non-cancerous tissues within resected lung nodules. We have implemented a processing pipeline which allows for the direct correlation between histological data and spatially corresponding computed tomography data. Utilizing these correlated datasets we evaluated the statistical separation between Hounsfield Unit (HU) histogram values for each tissue type. The findings of this study revealed that lung cancer nodules contain a complex intermixing of cellular tissue types and that trends exist in the relationship between these tissue types. It was found that the mean Hounsfield Unit values for isolated lung cancer nodules imaged with computed tomography, had statistically significantly different values for non-solid bronchoalveolar carcinoma, solid cancerous tumor, blood, and inactive fibrotic stromal tissue.     

Ephrin-as cooperate with EphA4 to promote trunk neural crest migration

Trunk neural crest cells delaminate from the dorsal neural tube and migrate on two distinct pathways: a dorsolateral route, between the ectoderm and somites,and a ventromedial route, through the somitic mesoderm. Neural crest cells that migrate ventromedially travel in a segmental manner through rostral half-somites, avoiding caudal halves. Recent studies demonstrate that various molecular cues guide the migration of neural crest cells, primarily by serving as inhibitors to premature pathway entry orby preventing neural crest from entering inappropriate territories. Trajectories of migrating trunk neural crest are well organized and generally linear in nature, suggesting that positive, migration-promoting factors may be responsible for this organized cell behavior. However, the identity of these factors and their function are not well understood. Here we examine the expression of members of the EphA subclass of receptor tyrosine kinases and ephrins using RT-PCR and immunocytochemistry. Neural crest cells express ephrins and EphA4 at distinct stages during their migration. In functional analyses, addition of ephrin-A2-, ephrin-A5-, and EphA4-Fc disrupted the segmental organization of trunk neural crest migration in explants: neural crest cells entered rostral and caudal halves of somites. Finally, to test the specific effects of these factors on cell behavior, neural crest cells were exposed in vitro to substrate-bound EphA and ephrin-As. Surprisingly, neural crest cells avoided ephrin-A2 or ephrin-A5 substrates; this avoidance was abolished by the addition of EphA4. Together, these data suggest that ephrin-As and EphA4 cooperate to positively promote the migration of neural crest cells through rostral half somites in vivo.     

Sling incision with associated vaginal wall interposition for obstructed voiding secondary to suburethral sling procedure

Obstructed voiding is a well recognized complication following a suburethral sling procedure. Current methods of transvaginal and transabdominal urethrolysis have had variable success rates in relieving the obstruction, and do not restabilize the urethra to prevent potential postoperative stress incontinence. We report on a procedure used in 4 cases which addresses both of these issues. All patients had persistent urinary retention beyond 8 weeks after a suburethral sling procedure. An oupatient procedure consisting of sling incision and associated tissue interposition (vaginal wall in three cases and fascia lata in one) was successful in relieving the obstruction. Continence status was maintained in 3 of the 4 patients. There were no major complications of this outpatient procedure.     

新缩瞳剂包公藤甲素人工合成研究

包公藤甲素是从包公藤(Erycibe obtusifolia Benth.)茎中提得的一个新莨菪烷生物碱,具有强烈的缩瞳作用,临床用于治疗青光眼。本文报道用合成的6β-乙酰氧基托品酮为原料,经卤代、水解、还原和N-去甲基化等反应合成包甲素(8)。经光谱测定证实8与天然包甲素的结构完全一致。合成品系外消旋体,其作用机理与天然品相同,而强度则减半。     

Mammalian motoneuron cell death: development of the lateral motor column of a wallaby (Macropus eugenii)

We have investigated the development of the lumbar lateral motor column of the tammar as a model of mammalian motoneuron cell death that is accessible to experimental manipulation. The tammar is an Australian marsupial, belonging to the subfamily of wallabies and kangaroos. After a gestational period of 26-28 days, the pup crawls to its mother's pouch using its forelimbs. The major morphometric events that shape the formation of the hindlimb occurred between 21 days gestation and birth. At birth the premuscle masses had divided and motor nerves had begun to penetrate the muscles of the thigh and shank. The period of motoneuron cell death was biphasic and occurred entirely postnatally. During phase I, between birth and 40 days, 59% of motoneurons were lost. Cell numbers then stabilised before falling a further 24%, to give an overall loss of 70%. Most of phase II cell loss occurred between 90 and 150 days. The possibility that a second period of motoneuron cell death may be a common feature of mammals is discussed.     

Development of skeletal muscles in transforming growth factor-beta 1 (TGF-beta1) null-mutant mice.

Fetal transforming growth factor-beta 1 (TGF-beta1) has been postulated to regulate the onset of myotube formation and/or pattern formation in developing skeletal muscles. In apparent contradiction of these hypotheses, the development of the extensor digitorum longus and soleus in TGF-beta1 null-mutant muscle was normal. The onset of secondary myotube formation, the numbers of myotubes formed, the proportion of fast and slow fibers, and the patterns of fiber types and connective tissues were essentially identical in TGF-beta1(+/+) and TGF-beta1(-/-) mice. A portion of the TGFbeta1 in skeletal muscles is derived from the mother, via the placenta. This maternal-derived TGF-beta1 was also not essential for the development of skeletal muscles, as the characteristics of pups born to a TGF-beta1(-/-) mother were normal TGF-beta1(-/-) mice die at weaning due to a generalized autoimmune attack. This postnatal death was circumvented by breeding the TGF-beta1 null mutation into nude mice (Whn(-/-)). Like many other strains of TGF-beta1(-/-) mice, extensive loss of Whn(-/-), TGF-beta1(-/-) embryos occurred in utero. However, a portion of the Whn(-/-), TGF-beta1(-/-) mice survived past weaning, remained healthy, and were fertile. The TGF-beta1(-/-) x Whn(-/-) mouse thus represents a valuable tool for the study of the function of TGF-beta1 in the adult, including its putative role as a pregnancy-related hormone.     

Characterization of a prostaglandin dysfunction myopathy

Inhibition of prostaglandin synthesis in chicken embryos generated a myopathy characterized by ringbinden, loss of Z disks and thick and thin filaments from the myofibrillar apparatus. During the early stages of myogenesis there was also abnormal clustering and contacts between the developing myotubes. This disruption of myofibrillar apparatus occurred in both primary and secondary myotubes. There was also a slight increase in the proportion of type 1 fibers, which resulted from a selective absence of type 2 fibers. The number of motoneurons in the lumbar spinal cord was normal. This, along with the nature of the disruption of the myofibrillar apparatus, was taken as an indication that the generation of this myopathy was not secondary to abnormal motoneuron development.