Mechanisms of failure in the repair of large retinal tears

An analysis of large tears treated over a decade revealed that while dialyses responded well to circumferential buckling, horseshoe tears responded poorly. A circumferential intrusion of the globe augmented the redundancy of the posterior edge of long tears and predisposed to leaking radical folds. Tears up to 70 degrees responded favorably to radical buckles, often without drainage of subretinal fluid. Beyond 70 degrees and initial procedure with cryopexy and a gas tamponade without buckling reattached the retina occasionally, and if not, would at least reduce the problem to one manageable by local buckling techniques with a more favorable prognosis.     

Mechanisms controlling cellular suicide: role of Bcl-2 and caspases

Apoptosis is an essential and highly conserved mode of cell death that is important for normal development, host defense and suppression of oncogenesis. Faulty regulation of apoptosis has been implicated in degenerative conditions, vascular diseases, AIDS and cancer. Among the numerous proteins and genes involved, members of the Bcl-2 family play a central role to inhibit or promote apoptosis. In this article, we present up-to-date information and recent discoveries regarding biochemical functions of Bcl-2 family proteins, positive and negative interactions between these proteins, and their modification and regulation by either proteolytic cleavage or by cytosolic kinases, such as Raf-1 and stress-activated protein kinases. We have critically reviewed the functional role of caspases and the consequences of cleaving key substrates, including lamins, poly(ADP ribose) polymerase and the Rb protein. In addition, we have presented the latest Fas-induced signalling mechanism as a model for receptor-linked caspase regulation. Finally, the structural and functional interactions of Ced-4 and its partial mammalian homologue, apoptosis protease activating factor-1 (Apaf-1), are presented in a model which includes other Apafs. This model culminates in a caspase/Apaf regulatory cascade to activate the executioners of programmed cell death following cytochrome c release from the mitochondria of mammalian cells. The importance of these pathways in the treatment of disease is highly dependent on further characterization of genes and other regulatory molecules in mammals.     

Mechanisms for the development of quinolone resistance

New fluoroquinolones have potent and broad antimicrobial activity and spectra, respectively, against gram-positive and -negative bacteria including P. aeruginosa. As a result of their frequent use, bacterial resistance to the quinolones has gradually developed and limited their therapeutic efficacy in infections, especially, with P. aeruginosa, S. pneumoniae, S. aureus (especially MRSA), and N. gonorrhoeae. Bacterial resistance to the quinolones probably results from : 1) mutations with chromosomal genes of DNA gyrase or DNA topoisomerase in E. coli and S. aureus, 2) decreased permeability of the cell envelope through OmpF, porin-forming protein, in gram-negative bacteria, and 3) activation of active efflux-mediated permeability through the cell membrane protein, either NorA in S. aureus or Opr in P. aeruginosa. Proper use of the quinolones is also proposed to prevent emergence of the bacterial resistance.     

Fibroblast dependency during early thymocyte development maps to the CD25+ CD44+ stage and involves interactions with fibroblast matrix molecules

We have investigated the role of specific components of the thymic stroma during development of CD4-8-T cell precursors by separating and reaggregating precursor subsets with individual or combinations of stromal cells. We show that while the development of CD25+ 44+ precursors is dependent upon a combination of major histocompatibility complex (MHC) class II+ thymic epithelial cells and fibroblasts, their direct descendants, CD25+ 44- precursors, develop to the CD4+ 8+ stage in the presence of MHC class II+ thymic epithelial cells alone. Thus, CD25+ 44+ precursors are the last developmental stage to be dependent upon fibroblast support. In addition, while metabolically inactive, 1-ethyl-3-(3'-dimethylaminopropyl) carbodiimide (ECDI)-treated fibroblasts retain the ability to promote T cell development, prior treatment with hyaluronidase abrogates this effect, suggesting that fibroblast-associated extracellular matrix components are the key elements involved. In support of this, we show that fibroblasts are located in cortical regions of the thymus where T cell precursors are known to reside, and that these fibroblasts are associated with an extensive extracellular matrix not found on thymic epithelial cells. Finally, antibodies to alpha 4 integrin and CD44 interfere with the efficiency with which CD4+ 8+ cells are generated from CD25+ 44+ precursors in reaggregate cultures and also reduce the binding of the latter to 3T3 fibroblasts, suggesting these molecules play a role in bringing T cell precursors into contact with fibroblast-associated extracellular matrix.     

Mechanisms of reflex development]

It is generally accepted that psychogenic voice disorder (PVD) is a result of psychosocial stress; however, systematic studies of etiological factors in this condition are few. Furthermore, although immediate effects of therapy are estimated to be good, relapses are frequent, and the long-term effects of therapy are not known. The present prospective and longitudinal study on 30 patients was thus focused on possible etiological factors, the course of therapy, and the long-term results of therapy for PVD. The results indicate that interpersonal conflicts related to family and work are of basic importance in precipitating this condition. PVD is interpreted as a specific disorder of verbal emotional expression. Our therapy model in which vocal exercises are performed, together with training of communicative skills, seems rewarding. Relapses were not reported in 88% of the patients during the followup period of 1.9-8.4 years after therapy.     

Signal-transduction pathways controlling light-regulated development in Arabidopsis

All metazoan cells are able to make decisions about cell division or cellular differentiation based, in part, on environmental cues. Accordingly, cells express receptor systems that allow them to detect the presence of hormones, growth factors and other signals that manipulate the regulatory processes of the cell. In plants, an unusual signal-light-is required for the induction and regulation of many developmental processes. Past physiological and molecular studies have revealed the variety and complexity of plant responses to light but until recently very little was known about the mechanisms of those responses. Two major breakthroughs have allowed the identification of some photoreceptor signalling intermediates: the identification of photoreceptor and signal transduction mutants in Arabidopsis, and the development of single-cell microinjection assays in which outcomes of photoreceptor signalling can be visualized. Here, we review recent genetic advances which support the notion that light responses are not simply endpoints of linear signal transduction pathways, but are the result of the integration of a variety of input signals through a complex network of interacting signalling components.     

Intrinsic and environmental factors in the development of functional maps in cat visual cortex

In the mammalian visual cortex, key neuronal response properties such as orientation preference and ocular dominance (OD) are mapped in an orderly fashion across the cortical surface. It has been known for some time that manipulating early postnatal visual experience can change the appearance of the OD map. Similar evidence for developmental plasticity of the orientation map has been scarce. We employed optical imaging of intrinsic signals to examine the contribution of intrinsic and environmental factors to the development of cortical maps, using the paradigms of strabismus, reverse occlusion and rearing in a single-orientation environment ('stripe-rearing'). For several weeks after induction of strabismus, the pattern of OD domains remained stable in young kittens. The isotropic magnification of the OD map matched the postnatal growth of the visual cortical surface during the same period. In reverse-occluded and in stripe-reared kittens, orientation preference maps obtained through the left and the right eye were very similar, although the two eyes had never shared any visual experience. We suggest that the geometry of functional maps in the visual cortex is intrinsically determined, while the relative strength of representation of different response properties can be modified through visual experience.     

Dendritic remodelling of retinal ganglion cells during development of the rat

Investigation of the morphology of ganglion cells in the cat retina has shown that a remarkable reduction in the number of dendritic spines and branches occurs during development of the alpha and beta cell classes. To learn whether dendritic remodelling represents a generalized mechanism of mammalian retinal ganglion cell development, we have examined the morphology of ganglion cells in the retina of the developing rat. The present study has concentrated on type II cells, which retain a great number of dendritic spines and branches in the adult and comprise a large proportion of the population of rat retinal ganglion cells. To reveal fine dendritic and axonal processes, Lucifer yellow was injected intracellularly in living retinae maintained in vitro. Size and complexity of the dendritic trees were found to increase rapidly during an initial stage of development lasting from late fetal life until approximately postnatal day 12 (P12). Dendrites and axons of immature ganglion cells expressed several transient morphological features comprising an excessive number of dendritic branches and spine-like processes, and short, delicate axonal sidebranches. The following developmental stage was characterized by a remarkable decrease in the morphological complexity of retinal ganglion cells and a slowed growth of their dendritic fields. The number of dendritic branches and spines of types I and II retinal ganglion cells declined after P12 to reach a mature level by the end of the first postnatal month. Thus, even cells that retain a highly complex dendritic tree into the adult state undergo extensive remodelling. These results suggest that regressive modifications at the level of the dendritic field constitute a generalized mechanism of maturation in mammalian retinal ganglion cells.     

Spatial and temporal expression of cone opsins during monkey retinal development

The primate retina requires a coordinated series of developmental events to form its specialized photoreceptor topography. In this study, the temporal expression of cone photoreceptor opsin was determined in Macaca monkey retina. Markers for mRNA and protein that recognize short wavelength (S) and long/medium wavelength (L/M) opsin were used to determine (1) the temporal and spatial patterns of opsin expression, (2) the spatial relationship between S and L/M cones at the time of initial opsin expression, and (3) the relative time of cone and rod opsin expression (Dorn et al. [1995] Invest. Ophthalmol. Vis. Sci. 36:2634-2651). Adult cone outer segments were recognized by either L/M or S opsin antiserum. Of all adult cone inner segments, 88-90% contained L/M opsin mRNA, whereas 10-12% contained S opsin mRNA. Fetal cones initially showed cell membrane as well as outer segment labeling for opsin protein, but cell membrane labeling disappeared by birth. No cones at any age contained markers for both S and L/M opsin mRNA or protein. S and L/M opsin protein appeared in the fovea at fetal day 75. Once opsin expression progressed beyond the fovea, both mRNA and protein for S opsin were consistently detected more peripherally than L/M opsin. Cones at the peripheral edge of S opsin expression had basal telodendria that appeared to reach toward neighboring cones. Because interactions between cone populations could organize the cone mosaic, the spatial relationship between S cones and the first cones to express L/M protein was analyzed quantitatively by using double-label immunocytochemistry. No consistent relationship was found between these two cone populations. Cones are generated at least 1 week before rods across monkey retina. However, rod opsin protein appears in and around the fovea at fetal day 66, 1 week before cone opsin protein. This suggests that independent local factors control differentiation in these two photoreceptor populations.     

The function of costimulatory molecules and the development of IL-4-producing T cells

In the observation of various opportunistic pathogens in HIV-positive persons, co-infection by Cryptococcus neoformans together with Mycobacterium avium intracellulare was found if there was a CD4 lymphocyte count as low as 3-20/microliters. In 1540 HIV-positive patients under treatment at a Berlin hospital (Auguste-Viktoria-Krankenhaus) during 1985-1994, all AIDS-relevant diseases were examined in a multivariate analysis as variables of influence on the manifestation of a systemic Mycobacterium avium complex (MAC) infection. The analysis involved data on 36 cases of cryptococcosis and 202 cases with a typical clinical course in whom MAC had been detected at sterile body sites. As significant and independent factors of influence, the following were identified: C. neoformans infection, wasting syndrome, lower age, low CD4 lymphocyte count and preceding Pneumocystis carinii pneumonia (PcP) prophylaxis. Cryptococcosis ranged first with an ods ratio of 2.75. The concomitant manifestation of cryptococcosis and systemic MAC infection in six patients is shown. Because both opportunists, C. neoformans and avian mycobacteria, may have their common habitat in droppings of defined species of pet birds, a common source of infection deserves further clinical and epidemiological attention.     

Response of retinal ganglion cell axons to striped linear gradients of repellent guidance molecules

The application of molecular biology in the study of the pathogenesis of herpes simplex virus type 1 (HSV-1) has led to significant advances in our understanding of mechanisms that regulate virus behavior in sensory neurons and epithelial tissue. Such study has provided insight into the relationship of host and viral factors that regulate latency, reactivation, and recurrent disease. This review attempts to distill decades of information involving human, animal, and cell culture studies of HSV-1 with the goal of correlating molecular events with the clinical and laboratory behavior of the virus during latency, reactivation, and recurrent disease. The purpose of such an attempt is to acquaint the clinician/scientist with the current thinking in the field, and to provide key references upon which current opinions rest.     

计算机联锁控制系统在安钢铁路站场的开发与应用

介绍了安钢渣铁站铁路信号计算机联锁控制系统的硬件结构和软件组成。并论述了系统的可靠性、安全性、实用性及取得的效益与效果     

A gene essential to brain growth and development maps to the distal arm of rat chromosome 12

Studies were undertaken to determine the stability of nitrobenzodiazepines and their 7-amino metabolites in water and blood. At 22 degrees C nitrazepam and clonazepam were stable in sterile fresh blood containing preservative over 28 days, whereas 25% of flunitrazepam was degraded. At 37 degrees C all three drugs were substantially lost over 9 h (29-51%). There was only a small loss observed for the 7-amino metabolites and no substantial amounts of parent drug and 7-amino metabolite were degraded in water under these conditions. In the absence of preservative substantial amounts (25-50%) of parent drugs were lost in fresh blood over 10 days at 22 degrees C. In bacterially-contaminated postmortem blood all three drugs were completely degraded over 8 h at 22 degrees C with almost all drug completely converted to the respective 7-amino metabolite. These metabolites were also partially degraded (10-20%) over 45 h at 22 degrees C. All 3 nitrobenzodiazepines were stable in blood stored for up to 24 months at -20 degrees C, or 4 degrees C over 10 months. Their respective 7-amino metabolites were, however, relatively unstable at -20 degrees C with a significant loss (29%) after 2 months. At 4 degrees C a 21% loss occurred after 1 month. Freeze/thawing was found not to affect the concentration of nitrobenzodiazepine and 7-amino metabolites. These results show that the nitrobenzodiazepines and their metabolites are unstable chemically and metabolically in blood. We advise that blood collected for the purpose of nitrobenzodiazepine determinations should be preserved with sodium fluoride, stored at -20 degrees C and assayed as soon as practicable, preferably within a week of collection.