Retinal remodeling in human retinitis pigmentosa.

Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies.

On the origin and variation of colors in lobster carapace.

The chemical basis of the blue-black to pink-orange color change on cooking of lobster, due to thermal denaturation of an astaxanthin-protein complex, α-crustacyanin, in the lobster carapace, has so far been elusive. Here, we investigate the relaxation of the astaxanthin pigment from its bound enolate form to its neutral hydroxyketone form, as origin of the spectral shift, by analyzing the response of UV-vis spectra of a water-soluble 3-hydroxy-4-oxo-ß-ionone model of astaxanthin to increases in pH, and by performing extensive quantum chemical calculations over a wide range of chemical conditions. The enolization of astaxanthin is consistent with the X-ray diffraction data of ß-crustacyanin (PDB code: ) whose crystals possess the distinct blue color. We find that enolate formation is possible within the protein environment and associated with a large bathochromic shift, thus offering a cogent explanation for the blue-black color and the response to thermal denaturation and revealing the chemistry of astaxanthin upon complex formation.

Increases in plasma sheet temperature with solar wind driving during substorm growth phases.

During substorm growth phases, magnetic reconnection at the magnetopause extracts ∼1015 J from the solar wind which is then stored in the magnetotail lobes. Plasma sheet pressure increases to balance magnetic flux density increases in the lobes. Here we examine plasma sheet pressure, density, and temperature during substorm growth phases using 9 years of Cluster data (>316,000 data points). We show that plasma sheet pressure and temperature are higher during growth phases with higher solar wind driving, whereas the density is approximately constant. We also show a weak correlation between plasma sheet temperature before onset and the minimum SuperMAG AL (SML) auroral index in the subsequent substorm. We discuss how energization of the plasma sheet before onset may result from thermodynamically adiabatic processes; how hotter plasma sheets may result in magnetotail instabilities, and how this relates to the onset and size of the subsequent substorm expansion phase.

Intense chorus waves are the cause of flux-limiting in the heart of the outer radiation belt.

Chorus waves play a key role in outer Van Allen electron belt dynamics through cyclotron resonance. Here, we use Van Allen Probes data to reveal a new and distinct population of intense chorus waves excited in the heart of the radiation belt during the main phase of geomagnetic storms. The power of the waves is typically ~ 2-3 orders of magnitude greater than pre-storm levels, and are generated when fluxes of ~ 10-100 keV electrons approach or exceed the Kennel-Petschek limit. These intense chorus waves rapidly scatter electrons into the loss cone, capping the electron flux to a value close to the limit predicted by Kennel and Petschek over 50 years ago. Our results are crucial for understanding the limits to radiation belt fluxes, with accurate models likely requiring the inclusion of this chorus wave-driven flux-limiting process, that is independent of the acceleration mechanism or source responsible for enhancing the flux.

Impact of national guidelines on family history breast cancer surveillance.

The breast cancer risk of women already under family history surveillance was accurately assessed according to national guidelines in an attempt to rationalize the service. Women attending two breast units in Glasgow between November 2003 and February 2005 were included. One thousand and five women under annual surveillance were assessed and had their relatives diagnoses verified. Four hundred and ninety-seven women were at significantly increased risk and eligible for follow-up. Five hundred and eight (50%) women attending were not eligible for family history surveillance, and 498 (98%) of these women accepted discharge. In conclusion, national guidelines have helped to more clearly define women who should undergo surveillance. This avoids unnecessary and potentially harmful routine investigations, and the service has been improved.

Extreme retinal remodeling triggered by light damage: implications for age related macular degeneration.

PURPOSE: Our objective was to comprehensively assess the nature and chronology of neural remodeling in retinal degenerations triggered by light-induced retinal damage (LIRD) in adult albino rodents. Our primary hypothesis is that all complete photoreceptor degenerations devolve to extensive remodeling. An hypothesis emergent from data analysis is that the LIRD model closely mimics late-stage atrophic age relared macular degeneration (AMD). METHODS: Sprague-Dawley (SD) rats received intense light exposures of varied durations and survival times ranging from 0 to 240 days. Remodeling was visualized by computational molecular phenotyping (CMP) of a small molecule library: 4-aminobutyrate (gamma), arginine (R), aspartate (D), glutamate (E), glutamine (Q), glutathione (J), glycine (G), and taurine (tau). This library was augmented by probes for key proteins such as rod opsin, cone opsin and cellular retinal binding protein (CRALBP). Quantitative CMP was used to profile 160 eyes from 86 animals in over 6,000 sections. RESULTS: The onset of remodeling in LIRD retinas is rapid, with immediate signs of metabolic stress in photoreceptors, the retinal pigmented epithelium (RPE), the choriocapillaris, and Müller cells. In particular, anomalous elevated aspartate levels appear to be an early stress marker in photoreceptors. After the stress phase, LIRD progresses to focal photoreceptor degeneration within 14 days and extensive remodeling by 60 days. RPE and choriocapillaris losses parallel Müller cell distal seal formation, with progressive neuronal migration, microneuroma evolution, fluid channel formation, and slow neuronal death. The remaining retina in advanced light damage can be classified as survivor, light damage (LD), or decimated zones where massive Müller cell and neuronal emigration into the choroid leaves a retina depleted of neurons and Müller cells. These zones and their transitions closely resemble human geographic atrophy. Across these zones, Müller cells manifest extreme changes in the definitive Müller cell tauQE signature, as well as CRALBP and arginine signals. CONCLUSIONS: LIRD retinas manifest remodeling patterns of genetic retinal degeneration models, but involve no developmental complexities, and are ultimately more aggressive, devastating the remaining neural retina. The decimation of the neural retina via cell emigration through the perforated retina-choroid interface is a serious denouement. If focal remodeling in LIRD accurately profiles late stage atrophic age-related macular degenerations, it augurs poorly for simple molecular interventions. Indeed, the LIRD profile in the SD rat manifests more similarities to advanced human atrophic AMD than most genetically or immunologically induced murine models of AMD.

A diagnosis of the plasma waves responsible for the explosive energy release of substorm onset.

During geomagnetic substorms, stored magnetic and plasma thermal energies are explosively converted into plasma kinetic energy. This rapid reconfiguration of Earth's nightside magnetosphere is manifest in the ionosphere as an auroral display that fills the sky. Progress in understanding of how substorms are initiated is hindered by a lack of quantitative analysis of the single consistent feature of onset; the rapid brightening and structuring of the most equatorward arc in the ionosphere. Here, we exploit state-of-the-art auroral measurements to construct an observational dispersion relation of waves during substorm onset. Further, we use kinetic theory of high-beta plasma to demonstrate that the shear Alfven wave dispersion relation bears remarkable similarity to the auroral dispersion relation. In contrast to prevailing theories of substorm initiation, we demonstrate that auroral beads seen during the majority of substorm onsets are likely the signature of kinetic Alfven waves driven unstable in the high-beta magnetotail.

Tolevamer, a novel nonantibiotic polymer, compared with vancomycin in the treatment of mild to moderately severe Clostridium difficile-associated diarrhea.

BACKGROUND: Current antibiotic therapies for Clostridium difficile-associated diarrhea have limitations, including progression to severe disease, recurrent C. difficile-associated diarrhea, and selection for nosocomial pathogens. Tolevamer, a soluble, high-molecular weight, anionic polymer that binds C. difficile toxins A and B is a unique nonantibiotic treatment option. METHODS: In this 3-arm, multicenter, randomized, double-blind, active-controlled, parallel-design phase II study, patients with mild to moderately severe C. difficile-associated diarrhea were randomized to receive 3 g of tolevamer per day (n = 97), 6 g of tolevamer per day (n = 95), or 500 mg of vancomycin per day (n = 97). The primary efficacy parameter was time to resolution of diarrhea, defined as the first day of 2 consecutive days when the patient had hard or formed stools (any number) or < or = 2 stools of loose or watery consistency. RESULTS: In the per-protocol study population, resolution of diarrhea was achieved in 48 (67%) of 72 patients receiving 3 g of tolevamer per day (median time to resolution of diarrhea, 4.0 days; 95% confidence interval, 2.0-6.0 days), in 58 (83%) of 70 patients receiving 6 g of tolevamer per day (median time to resolution of diarrhea, 2.5 days; 95% confidence interval, 2.0-3.0 days), and in 73 (91%) of 80 patients receiving vancomycin (median time to resolution of diarrhea, 2.0 days; 95% confidence interval, 1.0-3.0 days). Tolevamer administered at a dosage of 6 g per day was found to be noninferior to vancomycin administered at a dosage of 500 mg per day with regard to time to resolution of diarrhea (P = .02) and was associated with a trend toward a lower recurrence rate. Tolevamer was well tolerated but was associated with an increased risk of hypokalemia. CONCLUSIONS: Tolevamer, a novel polystyrene binder of C. difficile toxins A and B, effectively treats mild to moderate C. difficile diarrhea and merits further clinical development.

What effect do substorms have on the content of the radiation belts?

Substorms are fundamental and dynamic processes in the magnetosphere, converting captured solar wind magnetic energy into plasma energy. These substorms have been suggested to be a key driver of energetic electron enhancements in the outer radiation belts. Substorms inject a keV "seed" population into the inner magnetosphere which is subsequently energized through wave-particle interactions up to relativistic energies; however, the extent to which substorms enhance the radiation belts, either directly or indirectly, has never before been quantified. In this study, we examine increases and decreases in the total radiation belt electron content (TRBEC) following substorms and geomagnetically quiet intervals. Our results show that the radiation belts are inherently lossy, shown by a negative median change in TRBEC at all intervals following substorms and quiet intervals. However, there are up to 3 times as many increases in TRBEC following substorm intervals. There is a lag of 1-3 days between the substorm or quiet intervals and their greatest effect on radiation belt content, shown in the difference between the occurrence of increases and losses in TRBEC following substorms and quiet intervals, the mean change in TRBEC following substorms or quiet intervals, and the cross correlation between SuperMAG AL (SML) and TRBEC. However, there is a statistically significant effect on the occurrence of increases and decreases in TRBEC up to a lag of 6 days. Increases in radiation belt content show a significant correlation with SML and SYM-H, but decreases in the radiation belt show no apparent link with magnetospheric activity levels.

The crystal structure of Escherichia coli class II fructose-1, 6-bisphosphate aldolase in complex with phosphoglycolohydroxamate reveals details of mechanism and specificity.

The structure of a class II fructose-1,6-bisphosphate aldolase in complex with the substrate analogue and inhibitor phosphoglycolohydroxamate (PGH) has been determined using X-ray diffraction terms to a resolution of 2.0 A (1 A=0.1 nm). The crystals are trigonal, space group P3121 with a=b=78.24 A, c=289.69 A. The asymmetric unit is a homodimer of (alpha/beta)8 barrels and the model has refined to give R-work 19.2 %, R-free (based on 5 % of the data) 23.0 %. PGH resembles the ene-diolate transition state of the physiological substrate dihydroxyacetone phosphate. It is well ordered and bound in a deep polar cavity at the C-terminal end of the (alpha/beta)8 barrel, where it chelates the catalytic zinc ion using hydroxyl and enolate oxygen atoms. Trigonal bipyramidal coordination of the zinc ion is completed by three histidine residues. The complex network of hydrogen bonds at the catalytic centre is required to organise the position of key functional groups and metal ion ligands. A well-defined monovalent cation-binding site is observed following significant re-organisation of loop structures. This assists the formation of a phosphate-binding site on one side of the barrel that tethers PGH in the catalytic site. The positions of functional groups of substrate and putative interactions with key amino acid residues are identified. Knowledge of the complex structure complements the results of spectroscopic and site-directed mutagenesis studies, and contributes to our understanding of the mechanism and substrate specificity of this family of enzymes. A reaction mechanism distinct from that proposed for other class II aldolases is discussed. The results suggest that the class II aldolases should be sub-divided into two groups on the basis of both distinct folds and mechanism.

Tuberculosis deaths in countries with high HIV prevalence: what is their use as an indicator in tuberculosis programme monitoring and epidemiological surveillance?

Although the reduction of tuberculosis deaths is one of the aims of tuberculosis control, it has not always been a priority for National Tuberculosis Programmes (NTPs). The usual explanation is that death as a treatment outcome not associated with ongoing tuberculosis transmission is not relevant to the public health objective of cutting the cycle of disease transmission. However, death as an adverse outcome for tuberculosis patients and their families is an important indicator in NTP monitoring. Global health targets agreed as part of the Millennium Development Goals include the reduction of tuberculosis deaths. Tuberculosis deaths as an indicator of the impact of tuberculosis control measures are therefore important in the epidemiological surveillance of progress towards these targets. These considerations are particularly important in countries with high human immunodeficiency virus (HIV) prevalence where HIV has exacerbated the tuberculosis epidemic and is now the single best predictor of tuberculosis incidence. Tuberculosis deaths are also closely linked to HIV prevalence. Routine NTP data on tuberculosis cohort deaths are important in programme monitoring, and improvements in recording and reporting of deaths would help to overcome limitations in their accuracy. As routine NTP data on tuberculosis cohort deaths are insufficient as an indicator in epidemiological surveillance regarding the impact of NTPs on tuberculosis mortality, measuring progress towards targets for reduced tuberculosis deaths depends on improved national vital registration systems for a more accurate determination of tuberculosis mortality.

Statistical characterization of the growth and spatial scales of the substorm onset arc.

We present the first multievent study of the spatial and temporal structuring of the aurora to provide statistical evidence of the near-Earth plasma instability which causes the substorm onset arc. Using data from ground-based auroral imagers, we study repeatable signatures of along-arc auroral beads, which are thought to represent the ionospheric projection of magnetospheric instability in the near-Earth plasma sheet. We show that the growth and spatial scales of these wave-like fluctuations are similar across multiple events, indicating that each sudden auroral brightening has a common explanation. We find statistically that growth rates for auroral beads peak at low wave number with the most unstable spatial scales mapping to an azimuthal wavelength λ≈ 1700-2500 km in the equatorial magnetosphere at around 9-12 RE . We compare growth rates and spatial scales with a range of theoretical predictions of magnetotail instabilities, including the Cross-Field Current Instability and the Shear Flow Ballooning Instability. We conclude that, although the Cross-Field Current instability can generate similar magnitude of growth rates, the range of unstable wave numbers indicates that the Shear Flow Ballooning Instability is the most likely explanation for our observations.

Reduced postprandial skeletal muscle blood flow contributes to glucose intolerance in human obesity.

While it is well accepted that the disposal of an oral glucose load (OGL) occurs primarily in skeletal muscle, the mechanisms by which this occurs are not completely elucidated. Glucose uptake (GU) in skeletal muscle follows the Fick principal, such that GU equals the products of the arteriovenous glucose difference (AVGd) across and the blood flow (BF) into muscle. It is widely believed that in the postprandial period both insulin and glucose increase GU by increasing the AVGd; however, a role for increments in BF in the disposal and tolerance of an OGL has not been established. To investigate this issue, whole body GU (isotope dilution), leg GU (leg balance technique), leg BF, and cardiac index (CI) were measured after an overnight fast and over 180 min after an OGL (1 g/kg) in 8 lean (ln) and 8 obese (ob) subjects [mean +/- SEM age, 36 +/- 2 vs. 37 +/- 2 yr (P = NS) and 60 +/- 1 vs. 99 +/- 5 kg (P less than 0.01), respectively]. Serum glucose levels were higher in the ob than in the ln subjects between 100 and 160 min, indicating reduced glucose tolerance. Fasting and post-OGL serum insulin levels were 2- to 3-fold higher in ob vs. ln at all times, indicating insulin resistance. Peak (40-80 min) incremental whole body GU above baseline was 32% lower in ob vs. ln, (P less than 0.05). Peak femoral AVGd was not different between ob and ln (0.55 +/- 0.16 vs. 0.66 +/- 0.14 mmol/L; P = NS). Peak leg BF increased 36% over baseline in ln (0.328 +/- 0.052 to 0.449 +/- 0.073 L/min; P less than 0.05), while ob subjects displayed no change in leg BF from baseline. Consequently, peak leg GU was 44% lower in ob vs. ln (P less than 0.05). CI increased 24% from baseline at 60 min in ln (P less than 0.05), but was unchanged in ob. In summary, after an OGL 1) femoral AVGd increases in both ln and ob subjects, but skeletal muscle BF and CI increase in ln only; 2) since peak femoral AVGd values were similar in ln and ob, differences in peak leg GU and (by inference) whole body GU are largely due to reduced BF to insulin-sensitive tissues; and 3) hemodynamics play an important role in the physiological disposal of an OGL, and therefore, hemodynamic defects can potentially contribute to reduced glucose tolerance and insulin resistance.

Synaptic organization of enkephalinlike-immunoreactive amacrine cells in the goldfish retina.

Immunoelectron microscopy was used to examine the synaptic organization of enkephalinlike-immunoreactive amacrine cells in the goldfish retina. Enkephalin-immunostained processes sometimes contained dense-cored vesicles (115-145 nm) in addition to a generally homogeneous population of small, round, clear synaptic vesicles. A total of 194 synaptic relationships were observed that involved the immunostained processes of enkephalin-amacrine cells. The large majority of these were observed in sublayer 5 of the inner plexiform layer. In greater than 95% of the synaptic relationships, the enkephalin-immunostained profile served as the presynaptic element. In 58.8% of these relationships, enkephalin processes synapsed onto amacrine cell processes, while 30.4% of their synapses were onto processes that lacked synaptic vesicles. They also occasionally formed synaptic contacts (6.7%) onto the somas of cells located either in the inner nuclear or in the ganglion cell layers. Enkephalin profiles received synaptic input only from amacrine cells (4.1%), while no direct synaptic interaction was observed between enkephalin processes and bipolar cells. However, in sublayer 1, enkephalin profiles were found to synapse onto amacrine cell processes that were presynaptic to bipolar cell terminals. In the proximal inner plexiform layer, enkephalin processes were presynaptic to amacrine cell processes that as a group surrounded and sometimes provided synaptic input to extremely large and round bipolar cell endings.

The cerebellopontine system in the rat. I. Autoradiographic studies.

This study utilized light microscopic autoradiographic procedures to describe the projections from the three major subdivisions of the deep cerebellar nuclei (DCN) to the basilar pontine nuclei (BPN). Although the vast majority of cerebellopontine axons reached the BPN via the descending limb of the brachium conjunctivum (BC) after crossing the midline within the midbrain, a relatively small number of ipsilaterally projecting fibers was also observed. Fascicles of cerebellopontine axons left the main bundle of descending limb fibers throughout much of the rostrocaudal length of the BPN and passed around and through the medial lemniscus and cerebral peduncle to enter the pontine gray. The lateral cerebellar nucleus gave rise to the largest number of cerebellopontine fibers, whose terminal fields exhibited both diffuse and patchlike labeling patterns within each of the major subdivisions of the BPN including medial, ventral, lateral, and dorsal areas. Projections from the interpositus complex exclusive of its posterior division were fewer and less widely distributed than those from the lateral nucleus. Interpositopontine fibers terminated primarily in the caudal one-half of the BPN in medial, ventral, and lateral regions and overlapped somewhat with projections from the lateral cerebellar nucleus. Pontine projections emanating from the medial cerebellar nucleus were the fewest and most restricted in distribution relative to the other two cerebellar efferent systems. Such fibers formed a patchlike network of terminal fields which extended throughout much of the rostrocaudal length of the BPN in medial and dorsomedial regions. A relatively small but considerable number of ipsilateral cerebellopontine fibers terminated in pontine regions, which often mirrored the typical contralateral projection fields. Although it proved difficult to determine the precise origin of the ipsilateral fiber systems, it appeared that each of the three major DCN subdivisions made some contribution. Also it was apparent that considerable overlap existed between cerebellopontine projection zones and those of other pontine afferents including sensorimotor, visual, and auditory cortices, the superior colliculus, and the mammillary nuclei of the hypothalamus. Moreover, cerebellopontine terminal fields were congruent in some instances with discrete clusters of BPN neurons which serve as the source of pontocerebellar fiber systems, reaching portions of the lateral cerebellar hemispheres, posterior vermis, and the paraflocculus.

Interaction between enkephalin and gamma-aminobutyric acid in the chicken retina: a double-label immunoelectron microscopic analysis.

In the present study, double-label immunoelectron microscopy was used to examine the synaptic relationships between amacrine cell populations in the chicken retina that contain either enkephalin or gamma-aminobutyric acid (GABA) or both enkephalin and GABA. The objectives of the present study were twofold. First, the ultrastructural features and synaptic organization of enkephalin and enkephalin/GABA amacrine cells were compared. Second, the synaptic interactions between these populations and the population of GABA amacrine cells were examined. A total of 475 synaptic arrangements were observed to involved enkephalin or enkephalin/GABA amacrine cell processes. The synaptic relationships of enkephalin and enkephalin/GABA amacrine cells were quite similar. Each population was pre- and postsynaptic to amacrine cells, postsynaptic to bipolar cells, and presynaptic to processes possibly originating from ganglion cells. A substantial percentage of each population's pre- and postsynaptic relationships were with the processes of GABAergic amacrine cells. Moreover, when enkephalin and enkephalin/GABA amacrine cell processes were postsynaptic to bipolar cells, their dyadic partner was observed frequently to be a GABA amacrine cell process. The present study suggests a diversity in the population of chicken enkephalin amacrine cells with respect to their expression of the classical inhibitory transmitter GABA. Moreover, a functional relationship between enkephalinergic and GABAergic pathways is indicated by studies showing that both enkephalin and enkephalin/GABA amacrine cells exhibit substantial synaptic interaction with GABA amacrine cells.

The cerebellopontine system in the rat. II. Electron microscopic studies.

Cerebellopontine axonal boutons in the neuropil of the basilar pontine nuclei (BPN) were marked for ultrastructural identification by producing unilateral electrolytic lesions of the superior cerebellar peduncle (SCP) as it exited from the cerebellum and before its decussation in the caudal midbrain. Three varieties of degenerating boutons were distinguished on the basis of size, type of degeneration, and postsynaptic locus. A relatively large variety of bouton (2.5-6.0 microns) that exhibited filamentous degeneration throughout the range of survival times employed (1-14 days) was the most frequently observed type of degenerating cerebellopontine bouton. Such boutons formed synaptic contacts with several small, dendritic, spinelike profiles as well as the shafts of intermediate or proximal dendrites. A second, far less numerous and somewhat smaller type of bouton (1.5-4.5 microns) was distinguished by the fact that it exhibited advanced dark degenerative changes after a 2-day survival period, formed multiple spine contacts (but not shafts), and was no longer apparent in the neuropil after a postlesion survival time of 6 days. The third variety of degenerating bouton was small (0.8-2.0 microns), exhibited dark degeneration with a 2-6 day survival period, contacted primarily shafts of small-diameter dendrites, and was observed more frequently than the larger dark boutons but less often than the large filamentous boutons. All three types of degenerating boutons contained round, clear, synaptic vesicles and formed only asymmetric synaptic active sites. It is suggested that the three types of degenerating axon terminals arise from at least three varieties of neurons in the deep cerebellar nuclei. Further it is suggested that such boutons originate from cerebellar efferent axons which distribute in collateral fashion to the thalamus, red nucleus, and/or the inferior olive.

Localization of serotoninlike-immunoreactive amacrine cells in the larval tiger salamander retina.

Light microscopic immunocytochemistry was used to study the populations of serotoninlike-immunoreactive cells in the larval tiger salamander retina. Of 1,135 serotonin-immunostained cells observed in transverse cryosections, 87% were identified as amacrine cells, whereas 13% were tentatively designated as displaced amacrine cells. The somas of the vast majority of serotonin-amacrine cells were situated in the innermost cell row of the inner nuclear layer. Only a few serotonin-immunostained amacrine cell somas were observed in the second row of cells from the inner nuclear layer. Serotonin-immunoreactive processes generally appeared as a diffuse plexus distributed evenly throughout all levels of the inner plexiform layer. As determined in whole-mount preparations, serotonin-amacrine cells were divisible into two populations on the basis of the diameters of their somas. Large cells (45%) ranged from 16 to 19 microns in diameter with the vast majority measuring 17-18 microns. Smaller and sometimes less intensely stained cells ranged from 14 to 16 microns in diameter with the large majority measuring 15 microns. The diameters of serotonin-displaced amacrine cells ranged from 19 to 22 microns with the large majority measuring 20 microns in diameter. An examination of whole-mount retinas revealed that serotonin-immunoreactive amacrine and displaced amacrine cells were distributed throughout the center and the periphery of the retina. The density of serotonin-amacrine cells (large and small combined) was calculated to be 173 +/- 4.5 (mean +/- standard error) cells per mm2.

Projections to the basilar pontine nuclei from face sensory and motor regions of the cerebral cortex in the rat.

Orthograde axonal transport tracing methods were used to describe the projections to the basilar pontine nuclei (BPN) which arise within the face representation of motor or somatosensory cerebral cortex. Injections centered in motor face (MF) cortex resulted in the labeling of several corticopontine terminal fields which exhibit a rostrocaudal columnar arrangement within the ipsilateral BPN. The location of such terminal zones is consistent with the somatotopic pattern of termination previously described for limb sensorimotor cortices. In contrast, the projections from somatosensory face (SF) cortical regions largely terminate in BPN areas separate from those receiving either limb sensorimotor or MF inputs. Both MF and SF cortices also give rise to projections to the contralateral BPN; those from SF cortex are less extensive than those of MF origin. In addition to their relationship with limb sensorimotor corticopontine terminations, the MF projections to the BPN also seem to partially overlap the projection zones of the cerebellopontine system, particularly the regions projected upon by the lateral cerebellar nucleus. The SF projections, on the other hand, appear to terminate in BPN areas that also receive input from either the dorsal column nuclei or the spinal trigeminal complex. There is only minimal potential overlap between MF and SF projections in the BPN. With regard to the pontocerebellar system, the projections from MF cortex terminate among BPN neurons which project to the cerebellar hemispheres, particularly lobus simplex, crus I and crus II. The SF projections also overlap BPN neurons which project to the lateral hemispheres in addition to the paraflocculus and vermal lobules VII and IXa,b. Taken together these observations suggest that subsets of BPN neurons might exist such that some receive convergent inputs from systems whose function can generally be regarded as motor (sensorimotor cortex, cerebellopontine) while another population of BPN neurons might integrate signals from systems which transmit somatosensory information (dorsal column nuclei, spinal trigeminal).