Pathology forum: quiz case 1. Early medullary thyroid carcinoma (MTC), familial type, arising in a background of C-cell hyperplasia.
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Carcinoma, Medullary↗
Biomedical subjects
R W Allan
Publications and source records attributed to R W Allan.
Recombinants are isolated at high frequency following in vivo mixed ocular infection with two avirulent herpes simplex virus type 1 strains.
Mixed infections with different strains of herpes simplex virus type 1 (HSV-1) may result in more severe disease than infection with either strain alone. This phenomenon is important because it may facilitate the identification of virulence genes through the transfer of virulence determinants between complementing strains, and it may pose a problem in the use of attenuated HSV strains for vaccines and gene delivery vectors. In this study, we have compared the percentage of recombinants present after mixed infection with HSV-1 strains OD4 and 994 in vitro and in vivo. After corneal inoculation, we found that 74% of randomly picked isolates from the trigeminal ganglia were recombinants, compared with 59% from the cornea. Twenty-six percent of randomly picked isolates were recombinant following mixed infection of Vero cells in vitro. Seventeen recombinant strains isolated from the in vivo mixed infections were assayed for ocular virulence, and they were found to exhibit a wide range of virulence phenotypes. The presence of virulent recombinants suggests that recombination plays a role in the increased disease observed in this mixed infection, and the broad range of virulence indicates that there may be multiple genetic factors involved in the increased virulence observed after mixed infection with these two strains. The recombinants were also tested for their ability to grow in NIH 3T3 fibroblasts, and though some correlation was observed between growth in vitro and ability to cause ocular disease, improved growth in murine cells does not sufficiently explain the increased virulence observed in some recombinants.
3T3 Cells↗
One retroviral RNA is sufficient for synthesis of viral DNA.
We used previously characterized spleen necrosis virus-based retroviral vectors and helper cells to study the strand transfers that occur during the reverse-transcription phase of a single cycle of retroviral replication. The conditions used selected only for formation of an active provirus rather than for expression of multiple drug resistance markers. In nonrecombinant proviruses the minus- and plus-strand DNA primer transfers were almost completely intramolecular. However, as previously reported, recombinant proviruses contained approximately equal proportions of inter- and intramolecular minus-strand DNA primer transfers. Thus, we conclude that in the absence of recombination, one molecule of retroviral RNA is sufficient for viral DNA synthesis. Large deletions and deletions with insertions were detected primarily at a limited number of positions which appear to be hot spots for such events, the primer binding site and regions containing multiple inverted repeats. At these hot spots, the rate of deletions and deletions with insertions visible with PCR was about 10% per genome per replication cycle. Other deletions and deletions with insertions (detectable with PCR) occurred at a rate of about 0.5%/kb per replication cycle. Crossovers occurred at a rate of about 6%/kb per replication cycle under single-selection conditions. This rate is comparable to the rate that we reported previously under double-selection conditions, indicating that retroviral homologous recombination is not highly error prone. The combined rates of deletions and deletions with insertions at hot spots (10% per genome per replication cycle) and other sites (0.5%/kb per replication cycle) and the rate of crossovers (6%/kb per replication cycle) indicate that on average, full-size (10-kb) type C retroviruses undergo an additional or aberrant strand transfer about once per cycle of infection.
Animals↗
Copackaging of different-sized retroviral genomic RNAs: little effect on retroviral replication or recombination.
We tested the effect of copackaging retroviral vectors of different sizes on retroviral replication and recombination. Our results indicate little or no difference in replication or in the rate or pattern of the strand transfers leading to the formation of recombinant proviruses with size. The size difference of the vectors also allowed us to extend our previous analysis of the linkage of markers in the recombinant proviruses. We conclude that the observed linkage is inconsistent with the strand displacement/assimilation model of retroviral recombination.
Animals↗
Autoshaping the pigeon's gape response: acquisition and topography as a function of reinforcer type and magnitude.
The pigeon's key-pecking response is experimentally dissociable into transport (head movement) and gape (jaw movement) components. During conditioning of the key-pecking response, both components come under the control of the conditioned stimulus. To study the acquisition of gape conditioned responses and to clarify the contribution of unconditioned stimulus (reinforcer) variables to the form of the response, gape and key-contact responses were recorded during an autoshaping procedure and reinforcer properties were systematically varied. One group of 8 pigeons was food deprived and subgroups of 2 birds each were exposed to four different pellet sizes as reinforcers, each reinforcer signaled by a keylight conditioned stimulus. A second group was water deprived and received water reinforcers paired with the conditioned stimulus. Water- or food-deprived control groups received appropriate water or food reinforcers that were randomly delivered with respect to the keylight stimulus. Acquisition of the conditioned gape response frequently preceded key-contact responses, and gape conditioned responses were generally elicited at higher rates than were key contacts. The form of the conditioned gape was similar to, but not identical with, the form of the unconditioned gape. The gape component is a critical topographical feature of the conditioned key peck, a sensitive measure of conditioning during autoshaping, and an important source of the observed similarities in the form of conditioned and consummatory responses.
Animals↗
Alteration of location of dimer linkage sequence in retroviral RNA: little effect on replication or homologous recombination.
Retrovirus particles contain a dimer of retroviral genomic RNA. A defined region of the retrovirus genome has previously been shown to be important for both dimerization and encapsidation. To study the importance of the position of this encapsidation and dimerization signal for retroviral replication and homologous recombination, we used a previously described spleen necrosis virus-based helper cell system. This system allows retroviral vectors with multiple genetic markers to be studied after a single cycle of retroviral replication. The sequence responsible for dimerization, the encapsidation/dimer linkage sequence (E/DLS), was moved from its normal location near the 5' end of the retroviral genome to a location near the 3' end of the genome. We characterized four pairs of retroviral vectors: (i) with both E/DLSs at the 5' ends of the genomes, (ii) with both E/DLSs at the 3' ends of the genomes, and (iii) two with one E/DLS at the 5' end of the genome and one at the 3' end of the genome. We found that moving the E/DLS to the 3' end of the genome resulted in at most an approximately factor of 5 reduction in virus titer in a single cycle of retroviral replication. Furthermore, we found no changes that were attributable to the alteration of the position of the E/DLS in the minus-strand DNA primer transfers or the plus-strand DNA primer transfers, the rate of homologous recombination, or the number of internal template switches in recombinant proviruses. These results indicate that any alignment or conformation necessary for retroviral replication or recombination is not the result of the position of the E/DLS.
Animals↗
Selective sensitivity of schedule-induced activity to an operant suppression contingency.
The sensitivity of pigeons' schedule-induced activity to operant consequences was studied in two experiments. During a 30-s interval between food presentations, a keylight stimulus brightened incrementally. Stable terminal key pecking and interim locomotor activity developed. An operant "setback" contingency was applied to activity. The contingency arranged for locomotor movements (detected by a nine-panel floorboard) to be followed by a resetting of the keylight brightness to a dimmer value and a 1-s delay of reinforcement (for individual responses). Experiment 1 showed that activity patterns were highly sensitive to their operant consequences. Accompanying key-peck rates were only transiently affected. In Experiment 2, the setback contingency was imposed during restricted portions of the trial, and differential operant control of activity was demonstrated. However, birds in this study produced higher rates of key pecking as activity rates were reduced. These results suggest that although schedule-induced activity arises in response to the temporal arrangement of stimulus events, this behavior may retain considerable sensitivity to response-consequence relations.
Animals↗
Organization of the cerebellum in the pigeon (Columba livia): III. Corticovestibular connections with eye and neck premotor areas.
The connections of the cerebellar cortex with vestibular premotor neurons of the oculomotor and collimotor systems in the pigeon were delineated in experiments using WGA-HRP as an anterograde and retrograde tracer. Putative premotor neuron pools were identified by injections into the oculomotor (mIII) and trochlear nuclei (mIV) and into the most rostral portion of the cervical neck motor nucleus, nucleus supraspinalis (SSp). The retrograde data indicate that ipsilateral projections upon oculomotor neurons arise from the medial portions of the superior (VeS) and tangential (Ta) nuclei. Contralateral projections originate from the infracerebellar nucleus, the interstitial vestibular region including the main (lateral) portion of the tangential nucleus, and from the descending and medial vestibular nuclei (VeD, VeM). These projections were confirmed in anterograde studies that also defined the connections of these vestibular premotor regions with specific subnuclear divisions of the pigeon's "oculomotor" nuclei (mIII, mIV, mVI). The organization of projections from the vestibular nuclei to the pigeon's extraocular motoneurons is similar to that reported in mammals. Projections upon neck premotor neurons arise primarily from neurons in the interstitial region of the vestibular nuclear complex. After injections in SSp, retrogradely labeled neurons were found, contralaterally, in the lateral part of the tangential and superior vestibular nuclei and in the dorsolateral vestibular nucleus (VDL). Ipsilateral labeling was seen in the medial interstitial region (VeM, VeD, and medial Ta). These projections were confirmed in anterograde experiments. With the exception of VDL, vestibular nuclei projecting to neck motoneurons also project to extraocular motoneurons. Thus the infracerebellar nucleus projects exclusively, and the superior vestibular nucleus predominantly, upon oculomotor (mIII, mIV) nuclei; VDL projects predominantly upon the neck motor nucleus, whereas the interstitial vestibular regions (medial Ta, rostral VeD, intermediate VeM) project upon both collimotor and oculomotor neurons. The pattern of retrograde labeling seen in the cerebellar cortex after injections into vestibular premotor nuclei was used to define the projections of specific cerebellar cortical zones upon vestibular eye and neck premotor neurons. Corticovestibular projections upon these regions arise from the auricle and lateral unfoliated cortex, the posterior lobe components of cortical zones B and E, and from the vestibulocerebellum. Each of these cortical zones projects upon components of the vestibular nuclear complex, which are premotor to either oculomotor nuclei or collimotor nuclei. The hodological findings are related to the functional organization of the oculomotor and collimotor systems in the pigeon and compared with the mammalian data.
Animals↗
"Turning back the clock" on serial-stimulus sign tracking.
Two experiments examined the effects of a negative (setback) response contingency on key pecking engendered by a changing light-intensity stimulus clock (ramp stimulus) signaling fixed-time 30-s food deliveries. The response contingency specified that responses would immediately decrease the light-intensity value, and, because food was delivered only after the highest intensity value was presented, would delay food delivery by 1 s for each response. The first experiment examined the acquisition and maintenance of responding for a group trained with the contingency in effect and for a group trained on a response-independent schedule with the ramp stimulus prior to introduction of the contingency. The first group acquired low rates of key pecking, and, after considerable exposure to the contingency, those rates were reduced to low levels. The rates of responding for the second group were reduced very rapidly (within four to five trials) after introduction of the setback contingency. For both groups, rates of responding increased for all but 1 bird when the contingency was removed. A second experiment compared the separate effects of each part of the response contingency. One group was exposed only to the stimulus setback (stimulus only), and a second group was exposed only to the delay of the reinforcer (delay only). The stimulus-only group's rates of responding were immediately reduced to moderate levels, but for most of the birds, these rates recovered quickly when the contingency was removed. The delay-only groups's rates decreased after several trials, to very low levels, and recovery of responding took several sessions once the contingency was removed. The results suggest that (a) sign-tracking behavior elicited by an added clock stimulus may be reduced rapidly and persistently when a setback contingency is imposed, and (b) the success of the contingency is due both to response-dependent stimulus change and response-dependent alterations in the frequency of food delivery. The operation of the contingency is compared with the effects of secondary reinforcement and punishment procedures.
Animals↗
Prehension in the pigeon. I. Descriptive analysis.
Eating in the pigeon involves a series of jaw movements some of which serve a prehensile function; i.e., they are utilized in the grasping and manipulation of objects. These prehensile behaviors are extremely brief (30-80 ms), produce an adjustment of jaw opening amplitude to the size of the food object, are mediated by an effector system involving a relatively small number of muscles and are amenable to both "reflexive" and "voluntary" control. This combination of structural simplicity and functional complexity suggests that the pigeon's jaw movements may provide a useful "model system" for the study of motor control mechanisms in targeted movements. The present report provides a classification of jaw opening movements occurring during eating and a preliminary determination of the extent to which each movement class is scaled to the size of the food object. Jaw movements were monitored during responses to spherical food pellets of six different sizes (3.2-11.1 mm in diameter) using a transducing system which produces a continuous record of gape (i.e., interbeak distance). Assignment to movement classes was then carried out using a computer-assisted scoring program. Functions relating jaw opening amplitude to target size were determined for each movement class. Four jaw movement classes were identified: Prepecks (just prior to pecking), Grasps (opening movements made during pecking but prior to contact with the target), Mandibulations (movements serving to position and transport the object within the buccal cavity) and Swallows. For two of these movement classes (Grasps, Mandibulations) jaw opening amplitude is scaled to pellet size but the scaling functions differ in ways that reflect the functional requirements of the two behaviors.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Measurement and control of pecking response location in the pigeon.
Experimental arrangements for the detection and control of pecking response location in the pigeon are described. Two different, commercially available detection devices are compared, one utilizing an array of infrared light emitters and detectors (infrared device), the other requiring contact with sheets of conductive film (mylar device) but both specifying a location as a set of X-Y coordinates. The utility of these devices for monitoring peck location was assessed in experiments involving pecking responses emitted under continuous reinforcement, fixed ratio, and response differentiation schedules. Both devices allow measurement of responses over areas much greater than those of the standard pecking response key, provide information about the location of all responses, whether on or off a designated stimulus area, and permit the programming of reinforcement contingencies based upon peck location. While the two devices differ with respect to their sensitivity and their resolution, they yield similar distributions of peck locations for the same animal tested under similar reinforcement schedules. Both devices have some limitations related to their design as detectors of human touch, and suggestions for minimizing these limitations are presented.
Animals↗
Transfer of numeric ASCII data files between Apple and IBM personal computers.
Listings for programs designed to transfer numeric ASCII data files between Apple and IBM personal computers are provided with accompanying descriptions of how the software operates. Details of the hardware used are also given. The programs may be easily adapted for transferring data between other microcomputers.
Computers↗
"On-line" monitoring of jaw movements in the pigeon.
A system for the monitoring of jaw movements in the pigeon is described. A Hall-effect device mounted on the pigeon's upper beak is used to sense voltage changes induced by variations in the position of a magnet mounted on the lower beak. Analogue voltage changes are digitized and monitored by a microprocessor. The system produces data comparable to that obtained using high speed cinematography but permits "on-line" measurements of gape and increases the rapidity of data acquisition and analysis. It may be used to monitor beak movements during consumatory (eating, drinking) and conditioned (key-pecking) behaviors.
Animals↗
Rat stereotaxic surgery without earbars.
Described here is a rat headholding device intended for use in stereotaxic surgery. The assembly consists of a mouthpiece that accommodates the upper incisors and fits against the lateral and occlusive surfaces of the upper molars and of a contoured extension that is clamped down against the snout. To determine whether the apparatus could provide adequate stereotaxic support, we compared measures of skull displacement during surgery when using the "snoutclamp" and when using conventional earbars. Although the snoutclamp did not hold the head as rigidly as the earbar assembly did, the loss of accuracy was small. We judge that the snoutclamp can be used effectively as an alternative headholding device for many applications of stereotaxic surgery.
Animals↗
Rat stereotaxic surgery without earbars.
Described here is a rat headholding device intended for use in stereotaxic surgery. The assembly consists of a mouthpiece that accommodates the upper incisors and fits against the lateral and occlusive surfaces of the upper molars and of a contoured extension that is clamped down against the snout. To determine whether the apparatus could provide adequate stereotaxic support, we compared measures of skull displacement during surgery when using the "snoutclamp" and when using conventional earbars. Although the snoutclamp did not hold the head as rigidly as the earbar assembly did, the loss of accuracy was small. We judge that the snoutclamp can be used effectively as an alternative headholding device for many applications of stereotaxic surgery.
Animals↗
Diagnosis of recurrent desmoplastic small round cell tumor by fine needle aspiration. A case report.
BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a recently described neoplasm characterized by aggressive biology, occurrence in body cavities, expression of antigens from multiple cell lineages and a specific translocation between chromosomes 11 and 22. Most of the published information on this neoplasm is histologic. The case presented here enabled presentation of the cytomorphologic and immunocytochemical features of aspirated cytologic material obtained from this unique tumor. CASE: The cytologic, histologic, radiologic and clinical features of a DSRCT from a 17-year-old patient are presented. Although the initial diagnosis in this case was made on histology, recurrence was proven by fine needle aspiration biopsy (FNAB). CONCLUSION: The presence of sheets or clusters of small round malignant cells, associated with shards of dense fibroconnective tissue, in FNAB should lead the cytologist to consider the diagnosis of DSRCT.
Abdominal Neoplasms↗