The vertebrate retina is a distinctly laminar structure. Functionally, the inner plexiform layer, in which bipolar cells synapse onto amacrine and ganglion cells, is subdivided into two sublaminae. Cells that depolarize at light offset ramify in sublamina a; those that depolarize at light onset ramify in sublamina b. The separation of ON and OFF pathways appears to be a fundamental principle of retinal organization that is reflected throughout the entire visual system. We show three clear exceptions to this rule, in which the axons of calbindin-positive ON cone bipolar cells make ribbon synapses as they pass through the OFF layers with three separate cell types: (1) dopaminergic amacrine cells, (2) intrinsically photosensitive ganglion cells, and (3) bistratified diving ganglion cells. The postsynaptic location of the AMPA receptor GluR4 at these sites suggests that ON bipolar cells can make functional synapses as their axons pass through the OFF layers of the inner plexiform layer. These findings resolve a long-standing question regarding the anomalous ON inputs to dopaminergic amacrine cells and suggest that certain ON bipolar cell axons can break the stratification rules of the inner plexiform layer by providing significant synaptic output before their terminal specializations. These outputs are not only to dopaminergic amacrine cells but also to at least two ON ganglion cell types that have dendrites that arborize in sublamina a.

The increase in thickness of bronchial walls by such structural changes as subepithelial fibrosis contributes to the severity and chronicity of asthma by amplifying airway narrowing. However, the pathogenesis of this structural alteration is not known. Transforming growth factor beta 1 (TGF beta 1) is known to have biologic activities relevant to the cellular and molecular events in subepithelial fibrosis, such as the deposition of collagen I and III and the increase of myofibroblasts beneath the epithelial basement membrane. Therefore, we examined TGF beta 1 gene expression in bronchial biopsy tissues from five severe asthmatics, five mild asthmatics, and five normal subjects using in situ hybridization combined with histochemical staining. Cells expressing TGF beta 1 mRNA were detected in tissues from four normal subjects, one mild asthmatic, and five severe asthmatics. The density of positive cells in severe asthmatic tissues (52.1 +/- 22.7, mean +/- SD/mm2) was significantly greater than that in mild asthmatic tissues (1.0 +/- 1.9/mm2, P < 0.01) or normal tissues (10.5 +/- 10.6/mm2, P < 0.02). The density in mild asthmatic tissues was not significantly different from that in normal tissues. The vast majority of positive cells in severe (99.1 +/- 1.7%) and mild (100%) asthmatic tissues were identified as eosinophils. In contrast, eosinophils constituted a small portion of positive cells (20.8 +/- 21.6%) in normal tissues. These results indicated that TGF beta 1 mRNA was overexpressed in severe asthmatics and that the main source of the mRNA was eosinophils, suggesting that eosinophils play an important role in the pathogenesis not only of inflammation but also of structural changes, such as subepithelial fibrosis, in asthmatic airways.

Bronchial asthma is characterized by eosinophil infiltration and tissue remodeling. Matrix metalloproteinases (MMPs) are thought to play critical roles by degradating interstitial matrices in a wide range of lung diseases associated with reorganization of the airway architecture. To investigate whether MMPs are involved in the pathologic processes of bronchial asthma, we examined MMP expression in asthmatic subjects. In situ hybridization revealed abundant expression of MMP-9 (gelatinase B) mRNA in biopsy specimens from asthmatic subjects (n = 5), with an average positive cell distribution of 117.8 +/- 41.1 (mean +/- SEM)/mm2. In contrast, sparse expression of the mRNA (10.8 +/- 4.8 /mm2) was observed in specimens from normal subjects (n = 4). The vast majority of cells expressing the mRNA were eosinophils in asthmatic tissues (92.2 +/- 1.2%). MMP-9 protein, which was confined to the submucosal cells in the normal subjects, was not abundantly expressed in inflammatory cells, but there was positive reactivity for MMP-9 protein in the extracellular matrix. Immunoelectron microscopic analysis showed sparse immunolocalization of MMP-9 in the perinuclear spaces of eosinophils, but not in the granules. These findings suggest the overexpression of MMP-9 by eosinophils in bronchial tissues of asthmatic individuals, and the participation of MMPs in the pathologic changes in asthmatic airways.

This article reviews third-generation blood pumps, focusing on the magnetic-levitation (maglev) system. The maglev system can be categorized into three types: (i) external motor-driven system, (ii) direct-drive motor-driven system, and (iii) self-bearing or bearingless motor system. In the external motor-driven system, Terumo (Ann Arbor, MI, U.S.A.) DuraHeart is an example where the impeller is levitated in the axial or z-direction. The disadvantage of this system is the mechanical wear in the mechanical bearings of the external motor. In the second system, the impeller is made into the rotor of the motor, and the magnetic flux, through the external stator, rotates the impeller, while the impeller levitation is maintained through another electromagnetic system. The Berlin Heart (Berlin, Germany) INCOR is the best example of this principle where one-axis control combination with hydrodynamic force achieves high performance. In the third system, the stator core is shared by the levitation and drive coil to make it as if the bearing does not exist. Levitronix CentriMag (Zürich, Switzerland), which appeared recently, employs this concept to achieve stable and safe operation of the extracorporeal system that can last for a duration of 14 days. Experimental systems including HeartMate III (Thoratec, Woburn, MA, U.S.A.), HeartQuest (WorldHeart, Ottawa, ON, Canada), MagneVAD (Gold Medical Technologies, Valhalla, NY, U.S.A.), MiTiHeart (MiTi Heart, Albany, NY, U.S.A.), Ibaraki University's Heart (Hitachi, Japan) and Tokyo Medical and Dental University/Tokyo Institute of Technology's disposable and implantable maglev blood pumps are also reviewed. In reference to second-generation blood pumps, such as the Jarvik 2000 (Jarvik Heart, New York, NY, U.S.A.), which is showing remarkable achievement, a question is raised whether a complicated system such as the maglev system is really needed. We should pay careful attention to future clinical outcomes of the ongoing clinical trials of the second-generation devices before making any further remarks. What is best for patients is the best for everyone. We should not waste any efforts unless they are actually needed to improve the quality of life of heart-failure patients.

Many retinal ganglion cells are coupled via gap junctions with neighboring amacrine cells and ganglion cells. We investigated the extent and dynamics of coupling in one such network, the OFF α ganglion cell of rabbit retina and its associated amacrine cells. We also observed the relative spread of Neurobiotin injected into a ganglion cell in the presence of modulators of gap junctional permeability. We found that gap junctions between amacrine cells were closed via stimulation of a D 1 dopamine receptor, while the gap junctions between ganglion cells were closed via stimulation of a D 2 dopamine receptor. The pairs of hemichannels making up the heterologous gap junctions between the ganglion and amacrine cells were modulated independently, so that elevations of cAMP in the ganglion cell open the ganglion cell hemichannels, while elevations of cAMP in the amacrine cell close its hemichannels. We also measured endogenous dopamine release from an eyecup preparation and found a basal release from the dark-adapted retina of approximately 2 pmol/min during the day. Maximal stimulation with light increased the rate of dopamine release from rabbit retina by 66%. The results suggest that coupling between members of the OFF α ganglion cell/ amacrine cell network is differentially modulated with changing levels of dopamine.

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A magnetically levitated centrifugal blood pump (MedTech Dispo) has been developed for use in a disposable extracorporeal system. The design of the pump is intended to eliminate mechanical contact with the impeller, to facilitate a simple disposable mechanism, and to reduce the blood-heating effects that are caused by motors and magnetic bearings. The bearing rotor attached to the impeller is suspended by a two degrees-of-freedom controlled radial magnetic bearing stator, which is situated outside the rotor. In the space inside the ringlike rotor, a magnetic coupling disk is placed to rotate the rotor and to ensure that the pump head is thermally isolated from the motor. In this system, the rotor can exhibit high passive stiffness due to the novel design of the closed magnetic circuits. The disposable pump head, which has a priming volume of 23 mL, consists of top and bottom housings, an impeller, and a rotor with a diameter of 50 mm. The pump can provide a head pressure of more than 300 mm Hg against a flow of 5 L/min. The normalized index of hemolysis of the MedTech Dispo is 0.0025 +/- 0.0005 g/100 L at 5 L/min against 250 mm Hg. This is one-seventh of the equivalent figure for a Bio Pump BPX-80 (Medtronic, Inc., Minneapolis, MN, USA), which has a value of 0.0170 +/- 0.0096 g/100 L. These results show that the MedTech Dispo offers high pumping performance and low blood trauma.

Mammalian retinas contain about 20 types of ganglion cells that respond to different aspects of the visual scene, including the direction of motion of objects in the visual field. The rabbit retina has long been thought to contain two distinct types of directionally selective (DS) ganglion cell: a bistratified ON-OFF DS ganglion cell that responds to onset and termination of light, and an ON DS ganglion cell, which stratifies only in the ON layer and responds only to light onset. This division is challenged by targeted recordings from rabbit retina, which indicate that ON DS ganglion cells occur in two discriminably different types. One of these is strongly tracer-coupled to amacrine cells; the other is never tracer-coupled. These two types also differ in branching pattern, stratification depth, relative latency, and transience of spiking. The sustained, uncoupled ON DS cell ramifies completely within the lower cholinergic band and responds to nicotine with continuous firing. In contrast, the transient, coupled ON DS ganglion cell stratifies above the cholinergic band and is not positioned to receive major input from cholinergic amacrine cells, consistent with its modest response to the cholinergic agonist nicotine. Much data have accrued that directional responses in the mammalian retina originate via gamma-aminobutyric acid (GABA) release from the dendrites of starburst amacrine cells (Euler et al., 2002). If there is an ON DS ganglion cell that does not stratify in the starburst band, this suggests that its GABA-dependent directional signals may be generated by a mechanism independent of starburst amacrine cells.