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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↗

The neural substrate for the pupillary light reflex in the pigeon (Columba livia).

The neural substrate of the pupillary light reflex in the pigeon was investigated using anatomical, stimulation, and lesion techniques. In birds, as in mammals, the sphincter pupillae muscle (which constricts the iris) is innervated by cells in the ciliary ganglion (Pilar and Tuttle, '82). These cells are in turn innervated by cells in the Edinger-Westphal nucleus (EW) (Cowan and Wenger, '68; Narayanan and Narayanan, '76; Lyman and Mugnaini, '80). The efferent link of the pupillary light reflex must therefore involve cells in EW. To study the central course of this reflex pathway, injections of horseradish peroxidase (HRP) were placed in EW. These injections labeled cells in a number of regions including a contralateral pretectal nucleus, area pretectalis (AP). Only a limited number of cells in AP project to EW. Injections of tritiated amino acids into AP labeled a discrete region of the contralateral EW. This projection is confined to a dorsolateral region of caudal EW and overlies the somata of approximately 100 cells. Tritiated proline was injected into the eye, and the results confirmed an earlier report (Reperant, '73) that AP receives retinal input from the contralateral eye. Immunohistochemical studies demonstrated fibers in AP that stained positively for substance-P-like, enkephalin-like and tyrosine-hydroxylase-like immunoreactivity. Injections of HRP were placed in AP to examine the retinal ganglion cells mediating the reflex. Cells with an average diameter of approximately 14 microns (5-25 microns range) were labeled and averaged approximately 6 microns greater in diameter than the retinal ganglion cells (mean = 7.3 microns) labeled by an optic chiasm injection. The cells labeled by AP injections were distributed unevenly throughout the retina with a higher concentration in the central and temporal retina and a paucity in the red field and fovea. Our results demonstrate that AP receives input from a distinct subpopulation of large retinal ganglion cells that comprises a very small percentage of the total population of retinal ganglion cells. Unilateral lesions of AP abolished the pupillary light reflex in the eye contralateral to the lesion; stimulation of AP elicited pupilloconstriction in the eye contralateral to the stimulation site. These results delineate the central course of the pupillary light reflex pathway in the pigeon and identify the retinal ganglion cells that subserve this reflex. They show that, at every point in the pathway, only a few cells mediate this simple reflex.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Review of thoracic neuroblastoma.

Twenty-seven cases of thoracic neuroblastoma were reviewed. Thirteen cases (48%) survived, 11 for more than 2 years and two for more than 14 months. Surgery is the treatment of choice and complete excision appears to give the best result. However, radical surgery is discouraged if the tumor is not readily removable. The use of chemotherapy and radiotherapy should be limited to Stage III and Stage IV disease and for palliation of soft tissue and bony secondaries. The clinical presentation was generally non-specific with respect to the final diagnosis in this series. Significantly raised catecholamines were seen in 13 of 16 patients assessed (81%). Prognosis was related to the age at diagnosis, stage of disease and the histological type. The better prognosis seen in thoracic neuroblastoma in comparison with abdominal neuroblastoma may be related to the earlier presentation of the disease and the higher incidence of better differentiated tumours in the thorax. There appears to be an unknown additional factor that confers a better prognosis in patients under 1 year old.

Child↗

The discharge characteristics of vagal cardiac neurons during classically conditioned heart rate change.

Classically conditioned heart rate change in the pigeon has been developed as a vertebrate model system for cellular analysis of associative learning. One aspect of this development involved characterizing in detail the "final common path" for the conditioned response, the "cardiac motoneurons." With this as a foundation it has been possible to investigate the discharge properties of these motoneurons during acquisition of the conditioned heart rate response, and in this paper we report such data for the vagal (parasympathetic) component of the conditioned response. The activity of single neurons was recorded in the intermediate zone of the dorsal motor nucleus of the vagus of the pigeon. Antidromic activation confirmed that these cells gave rise to efferent axons in the vagus nerve and allowed their classification on the basis of conduction velocity into three groups: A, B1 (cardiac), and B2 units. B1 and B2 units had low levels of irregularly maintained activity, whereas A units discharged more regularly at higher frequency. B1 units had a weak cardiac rhythm, no respiratory rhythm, and showed decreased discharge in response to visual stimulation or foot-shock. These stimulus-evoked decreases in the activity of cardiac cells were accompanied by increases in heart rate. B2 units were unresponsive to both visual stimulation and foot-shock, whereas A units were unresponsive to visual stimulation but possibly responsive to foot-shock. The activity of vagal cardiac neurons was recorded during or after classical conditioning (paired lights and foot-shocks) or sensitization (unpaired lights and foot-shocks) to characterize discharge changes associated with conditioned cardioacceleration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Amyloid fibril in hereditary cerebral hemorrhage with amyloidosis (HCHWA) is related to the gastroentero-pancreatic neuroendocrine protein, gamma trace.

Amyloid fibrils were isolated from the leptomeningeal blood vessels obtained at autopsy from three Icelandic patients dying of Hereditary Cerebral Hemorrhage with Amyloidosis (HCHWA) and verified by Congo red staining and electron microscopy. Gel filtration on Sephadex and Ultrogel columns yielded predominantly one component (molecular weight 11,500 daltons) and also another minor component (molecular weight 15,800 daltons). Automated amino terminal sequencing showed these proteins to be similar (36 residues) to a recently described human protein, gamma trace, beginning at its eleventh amino terminal residue. The amyloid deposits in all three patients stained with rabbit anti-gamma trace antiserum. Although the function of gamma trace is not known, it appears to have structural homology with several hormones and has been localized to the brain, pancreas and pituitary. The amyloid fibril subunits seem to have polymerized after cleavage of the amino terminal decapeptide from gamma trace-related proteins. Therefore, HCHWA appears to be the first genetically determined disease related to the gastroenteropancreatic neuroendocrine system.

Adult↗