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Biomedical subjects

D H Cohen

Publications and source records attributed to D H Cohen.

At least 19 recordsLinked to original sources

Observations from the AAMC advisory panel on biomedical research.

The author gives a brief history of the events that led to the establishment of the Association of American Medical Colleges (AAMC) Advisory Panel on Biomedical Research, describes some of its early activities, and discusses some of the issues that the biomedical research community is facing. Specifically, he describes how the competition for research funding that became particularly intense in 1989-90 eroded the well-orchestrated coalition approach to appropriations that had been the norm. Another disturbing development was a growing tension between research faculty and the administrators of their institutions. To address these problems, the author, under the aegis of the AAMC, convened a series of workshops during the summer of 1990 to provide a forum for airing concerns and allowing different groups to become aware of each other's positions and perceptions. These workshops were quite useful and helped in framing some important issues. Also deriving from the workshops was the recognition that a continuing advisory group on research policy was needed; thus the AAMC advisory panel was created. The author describes its unusual characteristics and its importance. Subcommittees were later established to facilitate the effectiveness of the panel. Early in the panel's deliberations it became clear that it was important to bring into the meeting various knowledgeable individuals to educate and interact with panel members. The author concludes by surveying the larger picture of the public's eroding confidence in research universities and higher education in general, the punitive environment that this has created in Congress, the increasingly harsh economic situation, and what these conditions may portend for future research funding.

Financing, Government

Iontophoresis of norepinephrine onto neurons of the pigeon's lateral geniculate nucleus: characterization of an inhibitory response.

A group of neurons in the pigeon's lateral geniculate equivalent nucleus (LGNe) shows associative enhancement of their response to light during visually conditioned heart rate change. The source of the relevant unconditioned stimulus input to LGNe for this enhancement has been identified as the locus coeruleus (LC). Thus, we have begun to examine neurotransmitters synthesized in LC for possible involvement in associative modification of neuronal discharge in LGNe. As a first step, we have examined the responses of LGNe neurons to iontophoretic application of norepinephrine (NE) and identified the receptor mediating one response class. The majority of neurons in LGNe show inhibition of maintained activity in response to iontophoretic application of NE or its agonists. The potency of the NE agonists is alpha-methyl NE greater than epinephrine greater than NE greater than phenylephrine greater than isoproterenol. This profile is characteristic of an alpha 2-adrenoceptor. The alpha 2-agonist clonidine also induces inhibition of maintained activity. The alpha 2-antagonists WB-4101 and yohimbine block the NE-inhibition while the alpha 1-antagonist prazosin and beta-antagonist sotalol do not. It is thus suggested that the receptor mediating the NE-inhibition of maintained activity has the characteristics of an alpha 2-adrenoceptor.

Action Potentials

Group B streptococcus endocarditis following second-trimester abortion.

An 18-year-old woman who underwent an elective second-trimester abortion developed Streptococcus agalactiae (group B streptococcus) endocarditis characterized by a large, pedunculated vegetation involving a previously normal tricuspid valve. Polyarthritic symptoms, as well as multiple pulmonary emboli, were experienced, and cure followed a course of treatment using intravenous penicillin G potassium combined with gentamicin sulfate. Endocarditis caused by this pathogen usually occurs among individuals compromised by underlying chronic disorders and, today, is a rare sequela of pregnancy and abortion. When planning therapy, consideration should be given to the possibility of tolerance among clinical isolates and the need for operative intervention in selected patients.

Abortion, Induced

Retinal projections to the pretectum in the pigeon (Columba livia).

The retinal projection to the pretectum in the pigeon has previously been described in detail only by means of anterograde degeneration techniques (Repérant, '73). The present study reinvestigated these retinal projections by using the more sensitive anterograde autoradiographic technique. In general, our results confirm and extend those of Repérant ('73). We have found that three pretectal nuclei--the nucleus lentiformis mesencephali, tectal gray, and the area pretectalis--received heavy retinal input. A fourth pretectal nucleus, pretectalis diffusus, receives a slight retinal input. The nucleus lentiformis mesencephali can be divided into two closely apposed subnuclei that are cytoarchitecturally similar. We have termed them "lentiformis mesencephali, pars medialis" and "lentiformis mesencephali, pars lateralis." The tectal gray can be divided into a rostral, retinorecipient region and a narrow, caudal, nonretinorecipient region. The cytoarchitecture and retinal terminal field in area pretectalis have been described previously by us (Gamlin et al., '84). Pretectalis diffusus is located caudal to the retinorecipient dorsal thalamus and rostral to area pretectalis. Localized retinal injections of 3H proline delineated the number and extent of the retinal representations in the pretectum. Separate retinal representations were present in lentiformis mesencephali, pars medialis, lentiformis mesencephali, pars lateralis, the tectal gray, area pretectalis, and pretectalis diffusus. Only in the lentiformis mesencephali, pars medialis, lentiformis mesencephali, pars lateralis, and the tectal gray could the retinal representations be analyzed. Whereas the retinal representations in the lentiformis mesencephali, pars medialis and the tectal gray are comparable, the retinal representation in the lentiformis mesencephali, pars lateralis is different, being a mirror-image mediolaterally. In this study we introduce a conservative nomenclature for the retino-recipient pretectal nuclei that is consistent with earlier studies, in particular, those of Kuhlenbeck ('39), but has been modified in the light of our findings. We believe that this nomenclature, combined with the detailed cytoarchitectural descriptions provided, should facilitate future studies of the avian pretectum.

Animals

Projections of the retinorecipient pretectal nuclei in the pigeon (Columba livia).

We have used anterograde autoradiographic and retrograde HRP techniques to investigate the efferent connections of the retinorecipient pretectal nuclei in the pigeon. In the accompanying paper we identified these nuclei in the pigeon as the nucleus lentiformis mesencephali--pars lateralis and pars medialis, the tectal gray, the area pretectalis, and pretectalis diffusus. Although there are reports of a few of the projections of these nuclei, they had not previously been the subject of a detailed study. We found that different cell types in the lentiformis mesencephali, pars medialis and the lentiformis mesencephali, pars lateralis have descending projections to different targets. These targets include the inferior olive, the cerebellum, the lateral pontine nucleus, the nucleus papillioformis, the nucleus of the basal optic root, the nucleus mesencephalicus profundus, pars ventralis, the nucleus principalis precommissuralis, and the stratum cellulare externum. We found that a few cells in the lentiformis mesencephali project to the medial pontine nucleus, but that a much heavier projection arises from the nucleus laminaris precommissuralis, which is medial to the nucleus lentiformis mesencephali, pars medialis. The tectal gray has predominantly ascending projections to the diencephalon. The nuclei that it projects to are the nucleus intercalatus thalami, the nucleus of the ventral supraoptic decussation, the nucleus posteroventralis, the ventral lateral geniculate nucleus, the nucleus dorsolateralis medialis, and the nucleus dorsolateralis anterior. The tectal gray also projects topographically to layers 4 and 8-13 of the optic tectum. Area pretectalis has both ascending and descending projections. It has ipsilateral ascending projections to the nucleus dorsolateralis anterior, pars magnocellularis, the nucleus lateralis anterior, and the nucleus ventrolateralis thalami. It has ipsilateral descending projections to the central gray, the nucleus of the basal optic root, pars dorsalis, the lateral pontine nucleus, and the deep layers of the optic tectum. It has contralateral projections to the area pretectalis, the nucleus Campi Foreli, the interstitial nucleus of Cajal, the nucleus of Darkschewitsch, the cerebellum, and the Edinger-Westphal nucleus. The efferent projections of pretectalis diffusus are limited. It projects contralaterally to the pretectalis diffusus, and ipsilaterally to the nucleus of the ventral supraoptic decussation, the lateral pons, and the cerebellum.4

Animals

A second ascending visual pathway from the optic tectum to the telencephalon in the pigeon (Columba livia).

Previous studies in the pigeon (Karten and Revzin: Brain Res. 2:368-377, '66; Karten and Hodos: J. Comp. Neurol. 140:35-52, '70) have described an ascending tectofugal visual pathway from the optic tectum to the ectostriatum by way of the nucleus rotundus of the thalamus. This present study used anterograde autoradiographic and retrograde horseradish peroxidase pathway-tracing techniques to investigate another ascending tectofugal pathway in the pigeon. Injections of 3H-proline/leucine confirmed a previous report that the optic tectum projects to the nucleus dorsolateralis posterior of the thalamus (DLP). This projection is predominantly ipsilateral and is confined to a large-celled caudal region of the nucleus (DLPc); the rostral region of the nucleus (DLPr) is not tectorecipient. Injections of horseradish peroxidase in DLPc labeled cells predominantly ipsilaterally in layers 8-15 of the optic tectum. Injections of 3H-proline/leucine placed in the DLPc labeled a discrete region of the ipsilateral telencephalon. Similar injections of DLPr labeled a contiguous, but more rostral, region of the neostriatum intermedium. Nissl- and silver-stained material indicated that the region in which DLP terminates is cytoarchitecturally distinct from ventromedial ectostriatal core and belt. Injections of horseradish peroxidase at various locations in the neostriatal DLP terminal field demonstrated a rostrocaudal ordering of the DLP projection upon the neostriatum intermedium. Single-unit recording demonstrated that cells in DLPc respond to whole-field illumination at the same latency as cells in the nucleus rotundus, indicating that the tecto-DLPc-neostriatal pathway transmits visual information to the telencephalon. We suggest that comparable pathways may exist in both reptiles and mammals.

Animals

Characterization of tissue amyloid by immunofluorescence microscopy.

Immunohistochemical classification of amyloid type was possible in 44 of 50 (88%) patients as judged by the concordance of immunofluorescence, clinical, serum, and urine immunoelectrophoresis, and bone marrow data. In frozen tissue sections incubated with a panel of antisera monospecific for immunoglobulin heavy chains, kappa and lambda light chains, and amyloid-A-related protein, the amyloid was classified as AL in 20 and AA in 24. In 6 patients the amyloid could not be classified because of the absence of reactivity in 2 and overlap staining in 4. The findings indicate that routine immunofluorescence examination of diagnostic biopsies is an important adjunct in the classification of amyloid.

Adult

Modification of the discharge of lateral geniculate neurons during visual learning.

Visually conditioned heart rate change in the pigeon has been developed as a vertebrate model system for cellular analysis of associative learning. Previous studies have characterized the behavior, largely delineated the neural circuitry mediating the conditioning, and estimated the central processing time for the conditioned response. Most recently, this system has been used to investigate neuronal activity during conditioning along the visual pathways that transmit the conditioned stimulus (CS) information. It was first shown that neither maintained nor CS-evoked discharge of retinal ganglion cells changes during conditioning. Subsequently, we found that the thalamic and telencephalic components of the ascending tectofugal pathway show associative modification. We report here studies of the thalamofugal pathway, the avian homolog of the mammalian geniculocortical system. Single-cell activity was recorded in the thalamic relay of this pathway, the dorsal lateral geniculate equivalent (LGNe). This provided an opportunity to evaluate the generality of the training-induced modification found along the tectofugal pathway, and to determine if such modification occurs as peripherally as retinorecipient neurons. The results show that almost all LGNe neurons (97%) respond phasically to the onset of whole-field illumination. Most (94%) also respond to the unconditioned stimulus (US), footshock, some with increased and others with decreased discharge. Of cells receiving convergent input, those responding with decreased discharge to the US showed associative change (52%). Neurons that did not respond to both the CS and US, or that responded to the US with increased discharge, did not show associative modification. These findings suggest that the visual pathways transmitting CS information are not merely input lines, but undergo training-induced modification; such modification can occur as peripherally as the retinorecipient neurons of these pathways; and CS-US convergence is necessary but not sufficient for associative modification, since modifiability is apparently contingent on specific US response properties.

Analysis of Variance

Modification of neuronal discharge along the ascending tectofugal pathway during visual conditioning.

Visually conditioned heart-rate change in the pigeon has been developed as vertebrate model system for analysis of associative learning. The visual pathways transmitting the conditioned stimulus information were identified, and neurophysiological analyses during conditioning were then undertaken to determine if these pathways behave merely as input lines or undergo training-induced modification. After finding that the retinal output is invariant with training, we investigated the central visual pathways, beginning with the tectofugal pathway. During conditioning single neurons in the nucleus rotundus and ectostriatum, the thalamic and telencephalic relays of the tectofugal pathway, showed enhancement of their phasic light-evoked responses. In contrast, the initial phasic responses attenuated during non-associative training. The rate at which these discharge modifications developed paralleled the development of the behavioral response. Thus, the tectofugal pathway shows plasticity during conditioning and does not behave merely as an input channel for the conditioned stimulus.

Action Potentials

Invariance of retinal output during visual learning.

Visually conditioned heart-rate change in the pigeon has been developed as a vertebrate model system for the cellular analysis of associative learning. This development included identifying the visual pathways that transmit the conditioned stimulus information. That, in turn, established a foundation for neurophysiological analyses during conditioning to determine whether these pathways behave merely as input lines or undergo training-induced modification. We began this analysis at the visual periphery, the retina. By recording the activity of single optic tract fibers over the acquisition of the conditioned response it was demonstrated that neither the maintained nor CS-evoked activity of retinal ganglion cells are modified during non-associative or associative paradigms. Thus, the data (a) describe the temporal properties of the CS-evoked retinal response, (b) exclude various possibilities that might have modified this response during learning, and (c) establish a firm foundation for cellular neurophysiological analysis of central visual structures involved in transmitting the CS information.

Animals

Primary bone tumours in infants. Short literature review and report of 10 cases.

Ten cases of primary bone tumours in infants (1 osteosarcoma, 3 Ewing's sarcoma, 1 chondroblastoma and 5 angiomatosis) are reported. All cases of angiomatosis showed characteristic radiographic findings. In all the other tumours the X-ray appearances were different from those usually seen in older children and adolescents. In the authors' opinion the precise diagnosis of malignant bone tumours in infancy is very difficult as no characteristic X-ray features are present in this age period.

Angiomatosis

Gastric tube oesophagoplasty--a long-term assessment.

The first gastric tube oesophagoplasty at the Royal Alexandra Hospital for Children was performed in 1968. Over the next 15 years, until 1982, a total of 46 operations were performed. This represents the largest series of gastric tube oesophagoplasty in children yet reported in the literature. Two techniques have been in use and are compared. The main aim of the paper is to present the long-term results of gastric tube oesophagoplasty. In our 15 years' experience with the gastric tube for oesophageal replacement, we have found it to be a very satisfactory procedure, with a very low mortality and failure rate. The vascularity of the stomach gives rise to less anxiety than with colon. Early postoperative complications are readily identified and treated. There is a higher risk of serious chest complications in bringing the gastric tube through the chest with primary anastomosis in the neck. This also predisposes to diaphragmatic herniation and obstruction, complications not seen when the gastric tube is brought up substernally. The long-term results are very encouraging, with virtually all the children leading active and normal lives. The gastric tube functions satisfactorily with no evidence of the late complications often reported with colonic tubes. There is no significant difference in the long-term results of the two techniques of gastric tube oesophagoplasty used in this hospital.

Adolescent

Origin, course and terminations of the rubrospinal tract in the pigeon (Columba livia).

The red nucleus and its spinal projections in the pigeon (Columba livia) have been studied using both normal and experimental material. The cytoarchitecture of the nucleus is described on the basis of Nissl-stained sections and reveals an organization generally similar to that of mammals. The large neurons (40-50 mum) tend to be located dorsomedially and ventrolaterally at more caudal nuclear levels, while the small- and medium-sized neurons (15-35 mum) predominate at rostral levels. However, neurons of all sizes are present throughout the nucleus. Following lesions of the nucleus, the course of degenerating axons stained with the Fink-Heimer method has been traced throughout the brainstem and spinal cord. The rubrospinal tract crosses the midline, courses past the ventrocaudal aspect of the contralateral nucleus ruber, and then descends rostro-ventral and lateral to the nucleus tegmenti pontinus. In its caudal continuation the tract lies ventral to the brachium conjunctivum and the entering radix of the trigeminal nerve. It then assumes a ventrolateral position in the caudal brainstem before shifting to a dorsolateral position in the lateral funiculus of the spinal cord. Within the spinal grey the rubrospinal tract terminates in laminae V, VI and to a lesser extent VII. The possibility of a topographical organization of the nucleus was investigated with injections of horseradish peroxidase into brachial, thoracic and lumbar spinal cord. Regardless of the level of injection, labelled neurons of all sizes were present throughout the contralateral nucleus ruber, indicating the absence of an obvious topography.

Animals

Raphe inhibition of sympathetic preganglionic neurons.

Anatomical and electrophysiological studies suggest that the medullary raphe gives rise to a monosynaptic, inhibitory projection on sympathetic preganglionic neurons. Physiological and behavioral data indicate that this sympathoinhibitory pathway participates in the central control of cardiovascular function.

Animals

Electrophysiological and electron microscopic analysis of the vagus nerve of the pigeon, with particular reference to the cardiac innervation.

The compound action potential components and their associated fiber contingents were investigated in the pigeon vagus nerve with a view toward identifying the vagal cardioinhibitory fibers. In the cervical vagus, the compound action potential evoked by electrical stimulation included four major components that conducted at 17.0-30.0 (A-wave), 8.0-14.5 (B2-wave) and 0.8-2.0 (C-wave) m/sec. Cardiac slowing was not elicited until activation of the Bl-wave, and the bradycardic response was maximal when this component was maximized. Electron microscopic analysis of the cervical vagus revealed myelinated fibers 1.1-6.8 micron in diameter and unmyelinated fibers 0.3-1.4 micron in diameter. A contingent of myelinated fibers approximately 2-4 micron in diameter apparently generated the Bl-wave, while the prominent unmyelinated fiber contingent (37%) accounted for the C-wave. Analysis of various vagal branches indicated that approximatley 20% of the cervical vagal fibers exit the main trunk between cervical and mid-thoracic levels, but few of these are the larger myelinated fibers greater than 2 micron in diameter. The upper abdominal vagus consists largely of unmyelinated and small myelinated fibers, and consequently the vast majority of larger myelinated fibers found in the cervical vagus exit between mid-thoracic and upper abdominal levels, presumably in the cardiac branches. Direct examination of the cardiac branches confirmed this. Thus, it is concluded that the Bl-wave of the compound action potential is uniquely associated with cardiac slowing, that this component is generated by myelinated fibers ranging from 2 to 4 micron in diameter, and that almost all such fibers are destined for the cardiac branches of the vagus.

Action Potentials

Field potential and single unit analyses of the avian dorsal motor nucleus of the vagus and citeria for identifying vagal cardiac cells of origin.

Field potentials evoked by mid-cervical vagal stimulation were systematically mapped in the dorsal motor and solitary nuclei of the pigeon. Since responses varied predictably with microelectrode position, they could be used for localization in the dorsal medulla. By varying stimulus intensity and monitoring the vagal compound action potential, contributions of the different compound action potential waves were then established. Activation of the Bl-wave, which includes cardioinhibitory fiber activity, has its most prominent effect in the intermediate rostrocaudal zone of the dorsal motor nucleus in the region of subnuxleus b. This is where the cells of origin of the vagal cardiac fibers have previously been anatomically localized. Single unit experiments then established that (a) vagal motoneurons with axonal conduction velocities in the cardioinhibitory fiber range (8.0-14.5 m/sec) are primarily localized to the intermediate rostrocaudal zone of the dorsal motor nucleus in the region of subnucleus b, and (b) motoneurons in this zone that conduct at 8.0-14.5 m/sec distribute their axons in the cardiac branches. Furthermore, no error is introduced by identifying such neurons with mid-cervical rather than midthoracic vagal stimulation. Thus, the following criteria establish a neuron as giving rise to a vagal cardioinhibitory fiber: (a) localizing it to the intermediate rostrocaudal zone of the dorsal motor nucleus on the basis of the field potential evoked by mid-cervical vagal stimulation; (b) antidromically activating it with mid-cervical vagal stimulation; and (c) demonstrating that its axon conducts at 8.8-14.5 m/sec.

Animals

Avian sympathetic cardiac fibers and their cells of origin: anatomical and electrophysiological characteristics.

The sympathetic cardiac innervation of the pigeon was investigated to describe certain anatomical and physiological properties of the cardiac nerve fibers and their postganglionic cells of origin. The compound action potential of the right cardiac nerve has two major components, one conducting at 2.0-5.6 m/sec with no chronotropic effect on the heart and the other conducting at 0.4-1.0 m/sec with a cardioacceleratory effect. Postganglionic neurons responding antidromically to cardiac nerve stimulation were then studied in ganglion 14 which contains most cells of origin of the cardiac fibers. These neurons have refractory periods of approximately 4 msec, following frequencies of less than 4 HZ, and axons conducting at 0.4-2.0 m/sec; this conduction velocity range corresponds to the slower compound action potential component. Electron microscopy of the cardiac nerve revealed unmyelinated fibers ranging in diameter from 0.2 to 1.2 micrometer and a population of myelinated fibers 1.0-3.6 micrometer in diameter. The unmyelinated fibers account for the slower compound action potential component and are largely postganglionic cardioaccelerator axons. The myelinated fibers account for the faster compound action potential component which has no chronotropic effect and is not reflected in postganglionic antidromic latencies; it is suggested that these myelinated fibers are cardiac sympathetic afferents. This study thus establishes electrophysiological criteria for identifying cardiac postganglionic neurons and describes the anatomical basis of these criteria.

Animals