Current status of residency programs: survey of program directors.

RATIONALE AND OBJECTIVES: This survey was compiled to provide current data on the structure and content of radiology residency programs and the role of the residency program director. METHODS: A survey, created in electronic form and on paper, was distributed to all United States academic, private, and military radiology residency program directors. RESULTS: Of the 202 survey forms distributed, 168 (83%) were completed and returned. Eighty percent of respondents support national curriculum guidelines, but most do not favor national curriculum requirements. About half (53%) of programs spend 6 months in "view box" nuclear medicine; others provide some experience by lectures and on-call time. Most programs (60%) relieve residents of some call during the senior year. Some programs (28%) allow seniors time away from clinical duties to study for the oral board exam, and 17% permit time away to study for the written boards. Seventy-eight percent of programs have had a "problem resident," and 47% have asked a resident to leave the program. Directors' most frequently expressed concern was threat of diminished residency numbers due to decreased funding.

Cellulose as a gastrointestinal US contrast agent.

Ultrasound (US) imaging of the abdomen often is compromised by artifacts due to adjacent bowel gas. In an attempt to decrease gas artifacts and improve US image quality, the authors evaluated the use of cellulose preparations as gastrointestinal US contrast agents. Optimal homogeneity and reflectivity were evaluated in phantom solutions, and two suitable agents were selected for clinical trial. Ten volunteers underwent abdominal US imaging before and after contrast agent administration on three separate occasions. The volunteers drank 800 mL of freshly degassed water and two different gastrointestinal US contrast agents. US images obtained before and after administration of contrast material were evaluated by five radiologists and scored for bowel marking, visualization of abdominal anatomy, and image degradation by bowel gas. Compared with water, the orally administered US contrast agents improved visualization of bowel and abdominal anatomy, with diminished gas artifact.

Journal deselection in a biomedical research library: a mediated mathematical approach.

A unique mathematical formula was developed to use for journal deselection decisions. The formula factors in subscription cost, shelving and storage cost, interlibrary loan cost, staffing cost, and use level to determine the institutional cost ratio; this ratio serves as an indicator of the cost-effectiveness of each subscription title. Once the institutional cost ratio was calculated for each of 537 titles, a committee of library staff and senior library customers reviewed the ranked list to decide which subscriptions should be canceled. The committee also considered possible exceptions based on subjective criteria such as availability at local libraries, unrecorded use, and relative importance of the journal. The preliminary cancellation list was then reviewed by the library's research users. They were able to justify library subscriptions to a few additional titles. This method enabled the library to cut its subscription costs by 46%, while cutting only 8% of the total use. In addition, by mediating the mathematical approach with human intervention, the library made these severe cuts without unduly distressing its patrons.

Positional variations in germinal cell growth in pigment-chimeric eyes of Xenopus: posterior half of the developing eye studied in genetic chimerae and in computer simulations.

Growth of germinal cells at different angular positions within the posterior portion of the embryonic frog eye has been examined by orthotopically transplanting small groups of germinal cells from pigmented (stage 30-38) donor embryos into albino (stage 28-36) hosts and then serially photographing the polyclonal-cell progeny domain (typically a black sector) in the pigmented retinal epithelium of the living, growing eye. Far-ventral (6 o'clock) germinal cells formed a narrow sector along the ventral fissure, but ventral germinal cells at a position just posterior to the fissure (7 o'clock on a right eye) were seen to expand rapidly their angular territory on the germinal zone and formed huge sectors that widened toward the front of the older larval eye. Posterior (8, 9, and 10 o'clock) germinal cells were seen to shift their angular positions gradually toward dorsal and formed sectors that appeared to veer dorsalward nearing the front of the older eye. Dorsal (11 o'clock) germinal cells showed attenuative growth, forming sectors that narrowed approaching the front of the older eye. A simulation model of the growth dynamic was used to examine how expansive growth ventrally drives the positional variations in growth. When far-ventral germinal cells were programmed to retain the 6 o'clock position and ventral (7 o'clock) germinal cells were programmed to divide symmetrically at a high probability to produce two daughter germinal cells, not only were the observed ventral chimeric patterns simulated, but also simulated were the attenuative growth of dorsal transplants and the dorsal displacement and veering seen in the growth of posterior transplants.

Healing and growth of half-eye "compound eyes" in Xenopus: application of an interspecific cell marker.

Surgically constructed compound eyes have been widely used to examine the development of retinotectal projections in amphibians. Such studies have been limited, however, by the lack of an adequate cellular marker with which to assess the contributions of grafted and host tissues to the later larval and adult retina. We have followed the growth of graft- and host-derived ocular tissues in interspecific compound eyes prepared by orthotopic and heterotopic exchanges of half-eye fragments between pigmented Xenopus borealis and albino Xenopus laevis embryos. This genotypic combination allowed the growth of graft-derived choroid and pigment epithelium to be studied in the living animal, and permitted cell-by-cell resolution of graft- and host-derived neurons in quinacrine-stained paraffin sections. At mid- and late-larval stages graft-derived neurons occupied large and usually coherent territories of retina in all classes of orthotopic and heterotopic compound eyes. In successfully healed cases, sample means of the percentage of the total retina occupied by graft-derived neurons ranged from 43 to 51%. Graft-derived territories originated near the optic nerve head and extended into the germinal neuroepithelium at the retinal periphery. As compared to orthotopic compound eyes, graft-derived territories in all classes of heterotopic compound eyes were slightly smaller and significantly more variable. Despite this variability, the correlation between graft-derived pigment epithelial and retinal territories was quite good in heterotopic compound eyes. While graft-host borders were generally sharp, there was also evidence of local cell mixing over distances of several cell diameters in the inner nuclear and ganglion cell layers. Single displaced cells, isolated from other members of their genetic cohort by 5 or more cell diameters, were also present in the inner nuclear and ganglion cell layers.

Whole eyes reconstituted from embryonic half anlagen: alterations in donor-derived territories in Xenopus pigment chimerae.

Grafts from pigmented donor embryonic eye rudiments into albino hosts were used to chart i) fates of local cell groups in three positions in whole eye rudiments, and ii) alterations in graft-derived territories when the posterior half of the rudiment was ablated. Small pigmented patches of graft-derived tissue were conspicuous in albino embryos and tadpoles, enabling us to directly monitor their location and size in the eyes of living animals. The three (right eye) positions marked by pigmented grafts were dorsal (12 o'clock), anterior (3 o'clock), and anteroventral (5 o'clock). Control transplants reared without secondary ablation produced black sector territories in pigment retinal epithelium and iris at corresponding 12 o'clock or 2 o'clock or 4 o'clock positions on the larval eyeball. In the experimental series posterior half-anlagen were ablated. The remaining anterior half-anlagen, each containing a pigmented graft, reconstituted spherical larval eyeballs of reduced size. During healing, donor-derived pigmented sector territories remained coherent, but were altered in position and size compared to controls. Dorsal cells (from 12 o'clock grafts) appeared to move rapidly along the newly formed cut edge into the wound and went on to form expanded black sectors in posterior eye regions. More gradually, sector territories of anterior cells (3 o'clock grafts) and anteroventral cells (5 o'clock grafts) shifted toward dorsal in a counterclockwise direction. Thus all three types of graft derived pigment territories were altered in eye anlage fragments as they healed to form half-size spherical eyes.

Cell patterning in pigment-chimeric eyes of Xenopus: local cues control the decision to become germinal cells.

Between 2.5 and 4 days of development, cell proliferation in the Xenopus eye becomes confined to a narrow ring of germinal cells at the front rim of the eye cup. Continued growth of the eye (which lasts until well beyond metamorphosis) is by the continued proliferation of cells in this germinal zone. To determine what factor(s) promotes cell division in this region of the eye long after it ceases at the back of the eye (near the optic nerve), we have transplanted small groups of eye cells from pigmented donor embryos into the eyes of albino hosts, transposing cells from the mitotically quiescent back of the eye to the germinal zone and vice versa. Regardless of their position of origin in the donor eye, only implants into the host germinal zone behaved like germinal cells--as assayed in the living growing eye by the addition of black tissue to the pigment retinal epithelium. Conversely when donor germinal cells were implanted into the back of the host eye, they ceased dividing once they became integrated into the eye and remained as a tiny black spot on the back of the host eye. This suggests that local environmental cues, rather than intrinsic cellular determinants, specify the fates of eye cells ensuring that cells on the eye rim will continue to function as germinal cells while others will withdraw from the cell cycle.

Cell patterning in pigment-chimeric eyes in Xenopus: germinal transplants and their contributions to growth of the pigmented retinal epithelium.

We have examined the process by which small groups of pigmented germinal cells transplanted orthotopically from stage 30-38 donor embryos into stage 28-38 albino hosts contribute new postmitotic cells to the pigmented retinal epithelium of the growing larval eye in Xenopus. In the great majority of chimeric eyes, the transplant healed to occupy a small arc-territory at the intended dorsal or anterior position on the host germinal zone. Over the course of subsequent weeks, the transplanted germinal cells added new mitotically quiescent cells to the distal rim of the pigmented retinal epithelium and so gave rise to an elongating black sector on the growing larval eye. Cellular details at the boundaries of the graft-derived sector were stable over time; the accumulation of such landmarks provided a summary record--in the proximodistal axis of the older eye--of the growth history of the transplant. Case-to-case variation among both groups of transplants suggested a measure of indeterminancy in the details of germinal cell growth.

A physiological measure of shifting connections in the Rana pipiens retinotectal system.

The retinotectal connections of developing Rana tadpoles and froglets have been studied using light-pipe techniques to directly assay the pattern of the projection from the retina to the tectum. The projection site of the retina surrounding the optic nerve head was determined at two different stages of development (late larval and metamorphic frog) on the same animal. Small electrolytic marker lesions were used to mark the tectal sites to which the optic nerve head projected at these two times. Comparison of the positions of the two lesions gives a direct measure of the shift in the projection during the interlesion time interval of one week. The results indicate a shift in the projection of 275 micron week-1 in late larval life. Previous work in Xenopus using the light-pipe techniques indicated a qualitatively similar shift during equivalent stages of development, but significantly smaller in magnitude. In the present study, topographic postsynaptic units could be recorded at all stages investigated, indicating functional synapses between the optic nerve fibres and the tectum. Thus, these studies offer evidence of a significant shift in the functional connection pattern of the amphibian retinotectal map during development, in agreement with the recent anatomical data from other laboratories on the Rana and goldfish visual system.

Specific changes in axonally transported proteins during regeneration of the frog (Xenopus laevis) optic nerve.

Labeled proteins in intact and regenerating optic nerves of juvenile Xenopus clawed frogs were examined at three different time points (2 to 4 hr, 18 hr, and 5 to 9 days) following [35S]methionine injection into the eye. The distal axon tips of optic nerves were transected at the margin of the tectal lobe and regeneration of the nerve was followed by three methods: autoradiography, tissue section counting following [3H]proline injection into the eye, and electrophysiological mapping of the visual field projection. By these methods, regrowth was found to occur 2 weeks after transection, but the fibers had not yet sorted their retinotopic pattern. Two-dimensional gel separation of labeled nerve proteins revealed 250 to 300 identifiable proteins, 89 of which (including all spots which differed consistently upon direct comparison of regenerating versus normal nerves) were selected for quantitative treatment. Nine of these spots (240, 135, 65, 64, 58, 54, 56, 31, and 26 kilodaltons) were shown to increase and six (56, 49, 42, 29, 17, and 15 kilodaltons) were shown to decrease significantly in regenerating nerves. By using a crush control and tracking the labeled proteins into the tectum over time, these proteins were shown to be axonally transported proteins. In addition, four other nonaxonally transported proteins also changed during regeneration.

Application of reaction-diffusion models to cell patterning in Xenopus retina. Initiation of patterns and their biological stability.

We have examined the behavior of two reaction-diffusion models, originally proposed by Gierer & Meinhardt (1972) and by Kauffman, Shymko & Trabert (1978), for biological pattern formation. Calculations are presented for pattern formation on a disc (approximating the geometry of a number of embryonic anlagen including the frog eye rudiment), emphasizing the sensitivity of patterns to changes in initial conditions and to perturbations in the geometry of the morphogen-producing space. Analysis of the linearized equations from the models enabled us to select appropriate parameters and disc size for pattern growth. A computer-implemented finite element method was used to solve the non-linear model equations reiteratively. For the Gierer-Meinhardt model, initial activation (varying in size over two orders of magnitude) of one point on the disc's edge was sufficient to generate the primary gradient. Various parts of the disc were removed (remaining only as diffusible space) from the morphogen-producing cycle to investigate the effects of cells dropping out of the cycle due to cell death or malfunction (single point removed) or differentiation (center removed), as occur in the Xenopus eye rudiment. The resulting patterns had the same general shape and amplitude as normal gradients. Nor did a two-fold increase in disc size affect the pattern-generating ability of the model. Disc fragments bearing their primary gradient patterns were fused (with gradients in opposite directions, but each parallel to the fusion line). The resulting patterns generated by the model showed many similarities to results of "compound eye" experiments in Xenopus. Similar patterns were obtained with the model of Kauffman's group (1978), but we found less stability of the pattern subject to simulations of central differentiation. However, removal of a single point from the morphogen cycle (cell death) did not result in any change. The sensitivity of the Kauffman et al. model to shape perturbations is not surprising since the model was originally designed to use shape and increasing size during growth to generate a sequence of transient patterns. However, the Gierer-Meinhardt model is remarkably stable even when subjected to a wide range of perturbations in the diffusible space, thus allowing it to cope with normal biological variability, and offering an exciting range of possibilities for reaction-diffusion models as mechanisms underlying the spatial patterns of tissue structures.

Demonstration of a polarizing signal that reverses future retinotectal patterns across Nuclepore filter barriers, in Xenopus embryonic eye.

We have studied the interactions which occur in surgically disarranged eye rudiments by recombining a left anterior half-eye graft from a donor Xenopus embryo with a right host posterior half eye, across a variety of physical barriers, at embryonic stages 31 or 32. The anterior half-eye graft and barrier were removed 18 h later at stage 38, and the host posterior half-eye was allowed to reconstitute a whole eye whose visuotectal projection could be mapped electrophysiologically after metamorphosis. Anteroposteriorly reversed maps and double-anterior twinned maps that are characteristic of anterior half-eyes, were found in 50-65% of cases in each of the experimental series using no barrier (N = 16), or using Nuclepore filter barriers (N = 47), including 5 of 8 cases when a filter of 0.015 micrometer pore diameter was used. The latter cases are especially interesting, because the filter pores were much smaller than the minimum size known to permit cell-cell contact through the pores. No animals showed AP-reversed retinotectal maps or double-anterior twinned maps when the graft and host half-eyes were separated by a tantalum or plastic barrier (N = 21). Only a single case of AP-reversed mapping was found in 115 control animals including simple posterior half-eye preparations at stage 32 or 38 (N = 13), sham fusions (30 min) across Nuclepore filters (N = 35), or chronic application of a filter (or plastic or tantalum) barrier from stages 32-38 (N = 55) without a left anterior half-eye graft. We conclude that signals from an anterior half-eye can act to repolarize a posterior half-eye in the absence of cell transfer and under conditions which permit little or no direct cell-cell contact.

Axonal transport of [35S]methionine labeled proteins in Xenopus optic nerve: phases of transport and the effects of nerve crush on protein patterns.

Axonal transport of proteins in the Xenopus optic nerve was examined by labeling proteins in the eye with [35S]methionine injected intraocularly and then analyzing the labeled proteins in the eye, nerve, and tectum on linear gradient SDS polyacrylamide gels at different times after the injection. Because the optic nerve in Xenopus is short, in order to distinguish transported proteins from locally synthesized proteins, the optic nerve on one side of the animal was crushed at the orbit (to stop axonal transport) 5-30 min prior to injection and the crushed and normal nerve segments were compared. Proteins in the intact nerve which were absent in the crushed nerve were identified as axonally transported proteins. By such criteria several waves corresponding to transported material moving at greater than or equal to 6 mm/day, 1.6-2.8 mm/day, and approximately 0.2 mm/day were detected in the nerve. The most rapid phases of transport could be further resolved in the optic tectum into 3 additional components at 60-96 mm/day, 30-48 mm/day, and 6-11 mm/day. Analysis of labeled proteins in the crushed nerves distal to the crush, near the injury site, revealed several locally synthesized proteins (mol. wt. 54,000, 48,000, 43,000 daltons) which were not present in normal, uninjured nerves. Such proteins are probably synthesized by glia in response to injury.

The development of retinal ganglion cells in a tetraploid strain of Xenopus laevis: a morphological study utilizing intracellular dye injection.

The morphological development of retinal ganglion cells was examined in a tetraploid strain of Xenopus frogs. The enlarged cells of the tetraploid strain facilitate the application of intracellular techniques. Using an in vitro retinal preparation and Nomarski optics, intracellular recording and dye injection were carried out under visual control on ganglion cells in central retina from 2 days of development (stage 24) to metamorphosis (stage 64). We identified three phases in the morphological differentiation of ganglion cells. During the first phase (stages 24-30), all cells were neuroepitheliallike in form and possessed robust resting potentials in the range of -35 to -60 mV, and dye-coupling was occasionally observed between neighboring cells. During the second phase of ganglion cell development (stages 31-45) the neurons had begun to elaborate axons and dendrites. These cells possessing neurites had resting potentials between -15 and -30 mV, and no dye-coupling was observed between neighbors. During the third and final phase of maturation, from stage 46 onward, three distinct morphological types of ganglion cells could be identified. Type I cells had the smallest somata and the smallest-diameter dendritic arborizations. The profusely branched dendrites of these cells ramify extensively throughout the inner plexiform layer. Type II cells had large somata, intermediate-diameter dendritic fields, and a highly elaborate dendritic branching pattern. These cells were seen to arborize within two sublamina in the inner plexiform layer. Type III cells had large somata, the largest-diameter dendritic fields, and a dendritic arbor with long primary branches but little higher-order branching. These large dendritic fields were confined to a single sublamina of the inner plexiform layer, abutting the inner nuclear layer. While most phase 3 cells showed radial axon trajectories from the soma to the optic disc, a minority of cells (1-5%) with erratic and nonradial axon trajectories were also observed. Our data provide a morphological description of ganglion cell maturation in the central retina of Xenopus. We show that very early in development (as early as stage 46) three distinct morphological types of retinal ganglion cells are present, which correspond to the three classes of ganglion cells previously described in adult Xenopus (Chung et al., '75).

Spastic mutant axolotl: identification of a phenocopy pathway with implications for the control of axolotl swimming by the vestibulocerebellum.

The spastic mutant axolotl shows abnormal swimming behavior, which includes a preponderance of "embryonic" swimming elements (coils) versus mature swimming elements (sinusoids) and a failure to entrain sinusoids into a prolonged swimming sequence. The mutant also shows anatomical disorganization in the area acousticolateralis and cerebellar auricle, but it is unclear (1) to what extent the behavioral abnormalities are traceable to the vestibulocerebellar defect or (2) how the vestibulocerebellar pathway modulates swimming behavior in the normal axolotl. We have performed quantitative cine analysis of electric shock-induced swimming bouts in normal axolotls, spastic mutants, and a variety of neurosurgically altered wild-type axolotls. We scored the incidence of coil elements (25% in controls, 70-90% in spastics) versus sinusoid elements, as well as length distributions of coilfree intervals (short to long trains of sinusoidal swimming) and of sinusoidfree intervals (of brief of prolonged coiling). We found that bilateral VIIIth nerve lesions or surgical undercutting of the cerebellar auricle in wild-type axolotls almost exactly reproduced the behavioral deficit seen in spastic (75-81% coils, loss of long sinusoid trains, and appearance of prolonged coiling intervals at least some of which coupled several coils into trains of thrashing behavior). By contrast, neither complete transection of the CNS at low midbrain levels nor section of cranial nerves V, VII, or X (lateral line) resulted in an increased incidence of coil elements beyond 26% nor significantly altered the length distributions of S-intervals and C-intervals. Nor did any of the latter lesions disrupt the spasticlike swimming patterns of axolotls already subjected to auricle or VIIIth nerve lesions.(ABSTRACT TRUNCATED AT 250 WORDS)