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Biomedical subjects

C A Callahan

Publications and source records attributed to C A Callahan.

17 recordsLinked to original sources

Empathy in medical students as related to academic performance, clinical competence and gender.

CONTEXT: Empathy is a major component of a satisfactory doctor-patient relationship and the cultivation of empathy is a learning objective proposed by the Association of American Medical Colleges (AAMC) for all American medical schools. Therefore, it is important to address the measurement of empathy, its development and its correlates in medical schools. OBJECTIVES: We designed this study to test two hypotheses: firstly, that medical students with higher empathy scores would obtain higher ratings of clinical competence in core clinical clerkships; and secondly, that women would obtain higher empathy scores than men. MATERIALS AND SUBJECTS: A 20-item empathy scale developed by the authors (Jefferson Scale of Physician Empathy) was completed by 371 third-year medical students (198 men, 173 women). METHODS: Associations between empathy scores and ratings of clinical competence in six core clerkships, gender, and performance on objective examinations were studied by using t-test, analysis of variance, chi-square and correlation coefficients. RESULTS: Both research hypotheses were confirmed. Empathy scores were associated with ratings of clinical competence and gender, but not with performance in objective examinations such as the Medical College Admission Test (MCAT), and Steps 1 and 2 of the US Medical Licensing Examinations (USMLE). CONCLUSIONS: Empathy scores are associated with ratings of clinical competence and gender. The operational measure of empathy used in this study provides opportunities to further examine educational and clinical correlates of empathy, as well as stability and changes in empathy at different stages of undergraduate and graduate medical education.

Analysis of Variance↗

Monstrous attempts at adnexogenesis: regulating hair follicle progenitors through Sonic hedgehog signaling.

Epithelial organs such as the vertebrate hair control periodic self-renewal by regulating the growth of progenitor cells. Recent studies implicate Sonic hedgehog target gene induction in the growth of multipotent hair follicle epithelium and the development of a variety of hair follicle tumors such as basal cell carcinomas. These studies suggest Sonic hedgehog signaling may regulate progenitor cells in other organs.

Animals↗

Tracing axons.

For more than a century, neuroscientists have gained insight into brain function by examining its complex patterns of connectivity. To achieve this, a wide variety of axon-tracing techniques have been employed to chart the projections of neurons. New, experimentally flexible, reporter-based tracers, many of which are fusion proteins designed to target axons and dendrites, are being developed and are assisting the molecular characterization of the nervous system.

Animals↗

derailed is required for muscle attachment site selection in Drosophila.

During development, muscles must form and attach at highly stereotyped positions to allow for coordinated movements. In Drosophila, muscles grow towards and attach to specifically positioned cells within the epidermis. At the molecular level, very little is known about how muscles recognize these attachment sites. The derailed gene encodes a receptor tyrosine kinase family member that is essential for the pathfinding ability of expressing neurons. Here we show that the Drl RTK is also expressed by a small subset of developing embryonic muscles and neighboring epidermal cells during muscle attachment site selection. In drl mutants, these muscles often fail to attach at appropriate locations although their epidermal attachment cells appear unaffected. These results show that, similar to its role in neuronal pathway recognition, the Drl RTK participates in a mechanism required for muscle attachment site selection. The data suggest that both neurons and muscles use common mechanisms to recognize their paths or targets, and that Drl plays an analogous role in both developing systems.

Animals↗

Control of neuronal pathway selection by a Drosophila receptor protein-tyrosine kinase family member.

During development, neurons are capable of selecting specific pathways that lead them to their appropriate target areas. A variety of molecular mechanisms are thought to be involved in pathway recognition, including cell adhesion, repulsion and chemotropism. However, apart from a few genes whose involvement has been shown genetically, the mechanisms underlying neuronal pathway selection are largely unknown. Here we report the isolation of the Drosophila derailed (drl) gene, which encodes a novel member of the receptor protein-tyrosine kinase family. Using a newly developed axon-targeted reporter gene we find that drl is expressed by a small subset of embryonic interneurons whose growth cones choose common pathways during development. In drl mutant embryos these neurons fail to make the correct pathway choices. Our results provide evidence for receptor protein-tyrosine kinase involvement in key aspects of neuronal pathway recognition.

Amino Acid Sequence↗

Control of neuronal pathway selection by the Drosophila LIM homeodomain gene apterous.

The Drosophila apterous gene encodes a LIM homeodomain protein expressed embryonically in a small subset of differentiating neurons. To establish the identity of these neurons and to study the role of apterous in their development, we made apterous promoter fusions to an axon-targeted reporter gene. We found that all apterous-expressing neurons are interneurons that choose a single pathway within the developing central nervous system. In apterous mutants, these neurons choose incorrect pathways and fail to fasciculate with one another. Our results indicate that apterous functions to control neuronal pathway selection and suggest that other vertebrate and invertebrate members of the LIM homeodomain class of proteins may serve similar functions.

Animals↗

Tau-beta-galactosidase, an axon-targeted fusion protein.

The most commonly used enzymatic reporter molecule, Escherichia coli beta-galactosidase (beta-gal; beta-D-galactoside galactohydrolase, EC 3.2.1.23), fails to readily diffuse into axons; consequently, the morphologies of beta-gal-labeled neurons cannot directly be determined. For analysis of neuronal pathfinding and synaptic connectivity, this information is essential. We have constructed an axon-targeted beta-gal reporter by fusing the cDNA encoding the bovine microtubule-binding protein, tau, to lacZ, the E. coli gene encoding beta-gal. This reporter labels cell bodies and axons when expressed by developing and adult Drosophila neurons. It also reveals the entire cellular extent of nonneuronal cells such as muscle fibers and glia. To generate neuronal markers for studies of Drosophila neural development, we constructed a tau-beta-gal enhancer-trap transposon. From 1500 independent lines generated by mobilization of this transposon, we have isolated a set of useful markers for specific subsets of neurons, glia, and muscles. Since the tau cDNA-lacZ reporter utilizes bovine tau, it may also effectively target beta-gal in vertebrate neurons and prove to be a useful reagent for the analysis of vertebrate nervous systems.

Animals↗

Single-minded regulation of genes in the embryonic midline of the Drosophila central nervous system.

Proper development of the midline cells within the Drosophila central nervous system is controlled by the single-minded (sim) gene. The sim protein defines a new subclass of bHLH transcription factors and as such, is predicted to function as a transcriptional regulator of other genes important for midline development. Here we identify two potential targets of sim regulation: the sim gene itself, and the 47F gene, which is expressed specifically in the sim-expressing midline cells. Using a transgene containing sim regulatory sequences fused to beta-galactosidase, we show that the sim gene uses two distinct promoters with overlapping temporal specificities, and that expression from the late promoter is autoregulated by sim itself. By expressing sim protein in salivary gland nuclei using the heat-shock inducible Hsp70 gene promoter, we show that sim protein associates with the sim late promoter on polytene chromosomes. In addition, sim protein binds to a small number of additional chromosomal sites, among which are the sites of the 47F gene, and two other genes, Tl and cdi, whose expression also depend on sim function.

Animals↗

The contribution of NMDA and non-NMDA receptors to fast and slow transmission of sensory information in the rat SI barrel cortex.

The main objective of this study was to establish the contribution of NMDA receptors to natural processing of somatosensory information within rat SI barrel cortex. Responses of 52 cells in layers I-IV of the rat barrel cortex were analyzed by PSTH (peristimulus histogram) analysis of evoked spikes in reply to brief deflections of the principal whisker in animals anesthetized with urethane. Short and longer peak latency responses within PSTHs were compared in the presence and absence of the specific NMDA and non-NMDA antagonists D(-)-2-amino-5-phosphonovaleric acid and 6,7-dinitroquinoxaline-2,3-dione, which were administered locally to neurons by iontophoresis and additionally tested against their putative specific agonists, NMDA and quisqualate, respectively. The results suggest the following. (1) The generation of most spikes from cells in layers I-IV is dependent upon activation of NMDA receptors. However, NMDA receptors do not contribute to responses at very short latencies commensurate with monosynaptic thalamocortical relay for layer IV cells. These appear to be entirely mediated through non-NMDA receptors. (2) In the absence of transmission through NMDA receptors, non-NMDA receptors do not generate significant spike activity in later (10-100 msec latency) discharges. (3) NMDA receptor participation in first spike generation is directly dependent upon the latency of response of the cell to principal whisker deflection. (4) Latency of response, non-NMDA receptor-mediated spike generation and laminar location were powerfully covariant. (5) In addition, it was found that cells exhibiting short-duration spikes ( < 0.7 msec; "fast-spike units") in layer IV responded powerfully at short latencies, first spikes being entirely dependent upon non-NMDA but not NMDA receptor action, later spikes (10-100 msec poststimulus) being > 80% dependent upon NMDA receptor action. It is concluded that most sensorially driven spike activity in layers I-IV is dependent upon NMDA receptor action. This appears to be enabled by contingent subthreshold depolarization largely through non-NMDA receptor action, whereas the earliest thalamocortical discharges are evoked solely through non-NMDA receptors.

2-Amino-5-phosphonovalerate↗

Thalamo-cortical processing of vibrissal information in the rat. I. Intracortical origins of surround but not centre-receptive fields of layer IV neurones in the rat S1 barrel field cortex.

The receptive fields of cells restricted to the D1 cortical barrel territory in the S1 cortex of the rat were examined before and after substantial lesions of the D2 barrel. We tested 131 cells (N = 62, unlesioned controls; N = 69, lesioned animals) for modal latency and response magnitude to standard vibrissal deflections of 1.14 degrees. Lesions ranged in size to encompass 22-95% of the volume of the D2 barrel hollow and 5-75% of its neighbouring septal region, as calculated from cytochrome oxidase and Nissl staining of alternate sections. Negligible loss (mean 1.1%) of other barrel hollows and their septal regions (6.3%) occurred. A mean loss of 58% of the D2 barrel hollow and 27% of its accompanying septa was paralleled by a highly significant deficit in response magnitude (57.3%; p less than 0.005) of D1 barrel cells to D2 vibrissal stimulation, when compared with controls. The best-fit relationship between deficit and volumetric loss of the D2 barrel hollow was linear (regression coefficient -0.91). In the extreme case where 95% loss of D2 barrel hollow occurred, there was a 92% deficit in response of D1 barrel cells to the D2 input. No significant loss in response magnitude to other vibrissae, including the principal D1 input, occurred. Postlesioned animals exhibited some increase in excitability to the D1 vibrissa, and to vibrissae whose principal barrel territories were undamaged (delta, gamma, C1). Lesioning of the D2 barrel caused a highly significant mean increase (60%) in latency of residual responses to stimulation of the D2 vibrissal input (15.2 ms controls; 24.3 ms experimentals). No significant changes in response latency to other vibrissae compared to controls occurred. These results suggest that an intact D2 barrel is essential for the generation of responses of D1 barrel cells by the D2 vibrissa, and further imply that surround receptive fields of layer IV barrel cells are largely generated intracortically by barrel-to-barrel relay. The implications of these findings to cortical processing of tactile information and plasticity in the somatosensory system are discussed.

Afferent Pathways↗

Thalamo-cortical processing of vibrissal information in the rat. II. spatiotemporal convergence in the thalamic ventroposterior medial nucleus (VPm) and its relevance to generation of receptive fields of S1 cortical "barrel" neurones.

One hundred and twenty-six cells, sampled in the vicinity of the D1 barreloid in the ventroposterior medial nucleus of the thalamus, were tested for magnitude and latency of response to brief deflections (3 ms; 1.14 degrees) of vibrissae in adult rats under controlled conditions of light urethane anaesthesia. Similar results were achieved for D1 and non-D1-dominant cells. D1-dominant cells (N = 76) responded to the centre-receptive field (D1) vibrissa with a mean of 1.08 spikes per stimulus at modal latencies of 3-12 ms (inter-quartile range 4-5 ms) and to surrounding vibrissae with a mean of 0.26 spikes per stimulus at latencies of 3-41 ms (interquartile range 5-8 ms). Surround-receptive fields showed extensive overlap but were reduced and finally eliminated by deepening anaesthesia. A cell-by-cell analysis showed no correlation between latency and response magnitude for responses to surround vibrissae. Response magnitudes to the surround- and centre-receptive field inputs for D1-dominant barrel cells were some 2.5- and 1.7-fold greater, respectively, than for thalamic cells under identical experimental conditions. The latencies to centre- and surround-receptive field inputs for D1-dominant barrel cells were 2.5 and 10-20 ms later than for thalamus, respectively. These data on a mismatch of latencies for surround- and centre-receptive fields in thalamus and cortex support the notion that surround-receptive fields of cortical barrel cells are almost entirely constructed intracortically during light anaesthesia (Armstrong-James et al., '91), although it is argued that surround-receptive fields of thalamic cells conceivably could be relayed in other cortical states or serve a role in plasticity.

Afferent Pathways↗

New technique to completely isolate carotid sinus baroreceptor regions in rats.

We developed a method by which we can completely isolate the carotid sinus baroreceptor regions in the rat. The carotid sinus baroreceptor region is exposed and, with the use of extra-fine forceps, a human hair is placed around and tied at the root of the bifurcation. This procedure occludes the external carotid artery and blood flow to the carotid body. An injector is then attached to a catheter in the common carotid artery. We introduce a cylindrical rubber plug into either the palentine or internal carotid artery. A second plug is introduced to occlude the other artery. In six of the eight rats studied, these procedures completely isolated the carotid sinus region. In those cases where a small leak persisted at a carotid sinus pressure of 180 mmHg, we introduced a small particle of the animal's own previously clotted blood. Carotid sinus pressure was either randomly changed between 40 and 180 mmHg in 20-mmHg increments or in sequential 20-mmHg steps from 40 to 180 mmHg while measuring the animal's pulsatile and mean blood pressures. Arterial pressure-carotid sinus pressure relationship indicates that there is a highly sigmoidal relationship between the two pressures. The peak gain of the carotid sinus reflex system had a range from 1.5 to 4.0 and a mean value of 2.07 +/- 0.08. Our data indicate that the rat exhibits a significant carotid sinus baroreceptor reflex response. This technique combined with other techniques will allow for the study of neural control of cardiovascular function in the rat.

Animals↗

Pseudotumor cerebri and nutritional rickets.

A bulging fontanelle due to benign increased intracranial pressure is not generally recognized as a manifestation of nutritional rickets but should be considered in the appropriate clinical setting. Two children who we saw presented with bulging anterior fontanelles were found to have pseudotumor cerebri in association with nutritional rickets.

Humans↗