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Biomedical subjects

G Campbell

Publications and source records attributed to G Campbell.

At least 163 records · Page 9Linked to original sources

Metabolic origins of 5-hydroxytryptamine in enteric neurons in a teleostean fish (Platycephalus bassensis), a toad (Bufo marinus) and the guinea-pig.

1. 5-Hydroxytryptamine (5-HT) content and synthesis in mucosa-free intestine of guinea-pig, the teleost Platycephalus bassensis and the amphibian Bufo marinus was studied by HPLC with electrochemical detection or by TLC. 2. The 5-HT content of small intestine was: guinea-pig 0.58; Bufo: 1.23; Platycephalus: 26.88 nmol/g. 3. Intestine from each species synthesized 5-HT from exogenous 5-HTP. 4. Platycephalus preparations synthesized labelled 5-HT from 14C-tryptophan, but no labelled 5-HT was detected after similar incubation of guinea-pig or Bufo preparations. 5. Incubation of guinea-pig preparations with tryptophan did not increase tissue 5-HT or 5-HIAA content. 6. 5-HT in Platycephalus enteric neurons may be synthesized from tryptophan in situ; 5-HT in Bufo and guinea-pig neurons may be synthesized elsewhere, perhaps in enterochromaffin cells.

Animals↗

Progress on the CSE diagnostic study. Application of McNemar's test revisited.

The authors describe an extension of McNemar's test that can be used to compare diagnostic performance when multiple statements are obtained from computer analysis or visual interpretation of the ECG. If two or more diagnostic statements are made, by definition only one can be correct for the cases in the CSE pilot database, which were selected for single, clinically well documented, abnormalities. If one statement stood out from others as being made with the highest degree of certainty, that was accepted as the single interpretation, right or wrong. However, when two or more statements were made with the same degree of certainty and only one statement was correct, then in the previous application of McNemar's test that interpretation was given credit for being correct. In the extension of the method presented in this article, such an interpretation is given partial credit for the one correct statement and partial discredit for any incorrect statement, thereby reporting the results more properly in the sensitivity and specificity statistics for the different diagnostic categories.

Algorithms↗

Nonparametric comparison of entire ROC curves for computerized ECG left ventricular hypertrophy algorithms using data from the Framingham Heart Study.

A computer program may be capable of several different statements for left ventricular hypertrophy (eg, possible LVH, probable LVH, consistent with LVH), but such statements resulting from discretized levels of sensitivity/specificity would represent only isolated points on a receiver-operating characteristic (ROC) curve, which is a plot of all levels of sensitivity versus specificity. Even if two algorithms use the same discrete scales, their performances may not readily be compared. The authors present a comparison methodology for ROC curves using ROC area as a nonparametric measure of the ability of the algorithm to separate the two populations; the ROC area ranges from 0.5 (no ability) to 1.0 (perfect separation) and is unbiased if the normal versus abnormal populations have no common values for the measurement. The methodology compares the performance of ECG algorithms on the same population of cases by testing for significant differences of ROC areas and incorporating correlation of the algorithms in a nonparametric way. To illustrate this methodology, they use ECG and echocardiographic data from the Framingham Heart Study.

Algorithms↗

Retinal ganglion beta cells project transiently to the superior colliculus during development.

In adult cats, retinal ganglion cells of the beta class project almost exclusively to the lateral geniculate nucleus rather than to the superior colliculus (SC). We have examined whether this target specificity is present during early development. To identify ganglion cells that send axons to the SC in development, rhodamine-labeled microspheres were deposited in the SC at embryonic day (E) 38, E43, or postnatal day (P) 4. Retinae were then removed between E56 and P32 and kept alive in a tissue-slice chamber so that ganglion cells that had been retrogradely labeled with microspheres could be injected intracellularly with Lucifer yellow to reveal their morphological class. Many beta cells could be retrogradely labeled by microspheres injected into the SC at E38 or E43. They were indistinguishable from beta cells projecting to the lateral geniculate nucleus and were found even when a single injection was restricted to the caudal portion of the SC. In contrast, beta cells could not be retrogradely labeled by microspheres injected into the SC at P4. The disappearance of a beta-cell projection to the SC cannot be explained entirely by cell death since as late as P32, well after the major period of ganglion cell death, many beta ganglion cells labeled with microspheres at E38 were still present. These observations suggest that many beta cells initially extend an axon collateral to the SC that is subsequently lost some time after E43. Thus, to achieve the remarkable specificity present in the adult visual system, beta cells must withdraw axon collaterals from an entire target nucleus. Similar collateral elimination may give rise to the specificity of afferent connections in other sensory systems.

Animals↗

The effects of vagal stimulation and applied acetylcholine on the sinus venosus of the toad.

1. The effects of vagal stimulation and applied acetylcholine were compared on the isolated sinus venosus preparation of the toad, Bufo marinus. 2. The effects of applied acetylcholine and of low-frequency, or short bursts of high-frequency vagal stimulation were abolished by hyoscine. 3. When intracellular recordings were made from muscle cells of the sinus venosus, it was found that applied acetylcholine caused bradycardia and a cessation of the heart beat which was associated with membrane hyperpolarization and a reduction in the duration of the action potentials. Much of the effect of acetylcholine can be attributed to it causing an increase in potassium conductance, gK. 4. When slowing was produced by low-frequency vagal stimulation, only a small increase in maximum diastolic potential was detected. During vagal arrest the membrane potential settled to a potential positive of the control maximum diastolic potential. 5. In the presence of barium, much of the bradycardia associated with vagal stimulation persisted. Although the bradycardia produced by added acetylcholine also persisted in the presence of barium, the effects of acetylcholine that could be attributed to an increase in gK were abolished. 6. Addition of caesium ions produced bradycardia with membrane potential changes similar to those seen during vagal stimulation. 7. The results are discussed in relation to the idea that neuronally released acetylcholine reduces inward current flow during diastole. In contrast applied acetylcholine as well as reducing inward current flow during diastole also increases outward current flow by increasing gK.

Acetylcholine↗

Staining bacterial flagella easily.

A wet-mount technique for staining bacterial flagella is highly successful when a stable stain and regular slides and cover slips are used. Although not producing a permanent mount, the technique is simple for routine use when the number and arrangement of flagella are critical in identifying species of motile bacteria.

Alcaligenes↗

Synaptic organization of anomalous retinal projections to the somatosensory and auditory thalamus: target-controlled morphogenesis of axon terminals and synaptic glomeruli.

These experiments examine which morphological features of axon terminals and their synaptic glomeruli are determined by afferent axons, and which by their targets. In normal, adult hamsters, electron microscopy reveals that, with respect to multiple ultrastructural features, the terminals and synaptic glomeruli of retinal afferent axons in the dorsal lateral geniculate nucleus differ from those of ascending auditory and somatosensory afferents in the medial geniculate and ventrobasal nuclei, respectively. These features include: (1) the location of specific sensory axon terminals on the somata and dendrites of their targets neurons, (2) the constitutents of the glomeruli and their synaptic relationships, (3) the number of specific sensory terminal boutons per glomerulus, (4) bouton size, (5) the number of dendritic and somatic appendages contacted by each bouton, and (6) the mitochondrial morphology of the specific sensory afferent boutons. In order to ascertain which of these features are determined by afferent axons and which by their targets, we subjected newborn Syrian hamsters to surgical procedures known to produce permanent, abnormal retinal projections to the main thalamic auditory (medial geniculate) and somatosensory (ventrobasal) nuclei. When the animals were adults, we examined the terminals and synaptic glomeruli of abnormal retino-auditory and retino-somatosensory axons that were anterogradely labeled by intraocular injection of horseradish peroxidase. With respect to all of the preceding features except mitochondrial morphology, the terminals and synaptic glomeruli of retino-medial geniculate and retino-ventrobasal axons more nearly resembled those of normal, auditory and somatosensory afferent axons, respectively, than they did those of normal, retino-lateral geniculate axons. These results demonstrate that the differentiation of all the features that we have examined, except mitochondrial morphology, is determined by factors in target neurons or their environment. This finding suggests that the differentiation of morphological features involved in contacts among neurons (including the type, number and size of interconnected neuronal elements and the loci at which they contact each other) is responsive to interactions among the connected elements, or between neural elements and their environment (e.g., glia, extracellular matrix), whereas the differentiation of structures reflecting intrinsic functions of individual neuronal elements is not responsive to such interactions.

Animals↗

The distribution of 5-hydroxytryptamine in the gastrointestinal tract of reptiles, birds and a prototherian mammal. An immunohistochemical study.

The distribution of 5-hydroxytryptamine in the gut of several species of birds and reptiles, and of a prototherian mammal, the platypus, was studied using a monoclonal antibody. 5-Hydroxytryptamine-like immunoreactivity was found in enterochromaffin cells and, in birds, in thrombocytes. Immunoreactivity was not found in enteric neurons fixed immediately after dissection. A detailed study was made on one avian species, the budgerigar. Following incubation of intestine in physiological solution, immunoreactivity was found in nerve fibres in the gut wall that was more marked after incubation with the monoamine oxidase inhibitor pargyline. These fibres took up exogenous 5-hydroxytryptamine. Similar fibres were found in the intestinal nerves and in perivascular plexuses on mesenteric arteries. Both the uptake of 5-hydroxytryptamine and the appearance of neuronal immunoreactivity after incubation were inhibited by the amine uptake inhibitors desmethylimipramine or fluoxetine. Fibres taking up 5-hydroxytryptamine were damaged by pretreatment with 6-hydroxydopamine. It was concluded that the fibres showing immunoreactivity after incubation were adrenergic fibres that had taken up 5-hydroxytryptamine released in vitro from enterochromaffin cells or thrombocytes. These, and more limited observations made on the other species, suggest that birds, reptiles and prototherian mammals lack enteric neurons that use 5-hydroxytryptamine as a transmitter substance.

Animals↗

Immunohistochemical study of 5-HT-containing neurons in the teleost intestine: relationship to the presence of enterochromaffin cells.

The formaldehyde-induced fluorescence technique had shown 5-hydroxytryptamine-containing enteric neurons in the intestine of the teleost Platycephalus bassensis, but did not reveal such neurons in the intestine of Tetractenos glaber or Anguilla australis. Re-examination of these animals with 5-hydroxytryptamine immunohistochemistry showed immunoreactive enteric neurons in the intestine of all three teleost species. The 5-hydroxytryptamine-containing enteric neurons showed essentially the same morphology in all species examined: the somata were situated in the myenteric plexus, extending down into the circular muscle layer, but none were found in the submucosa; processes were found in the myenteric plexus, the circular muscle layer and the lamina propria. It was concluded that the neurons may innervate the muscle layers or the mucosal epithelium, but were unlikely to be interneurons. In a range of teleosts, enterochromaffin cells were found in the intestine of only those species in which the formaldehyde technique did not visualize neuronal 5-hydroxytryptamine. Available evidence suggests that, in vertebrates, 5-HT-containing enterochromaffin cells are lacking only where there is an innervation of the gut mucosa by nerve fibres containing high concentrations of 5-HT.

Animals↗

Dendritic invagination of developing optic tract axons in the hamster.

Between E15 and P4 in the hamster, axons of retinal ganglion cells in the optic tract over the dorsal lateral geniculate nucleus, are invaginated by, and make synaptic contacts with, small processes interpreted as tips or appendages of geniculate dendrites. In some cases a branch-like protrusion emerges from the axon at or close to the invagination. We hypothesize that the invaginations may be part of the mechanism by which retinocollicular axons are induced to branch and establish the retinogeniculate pathway.

Animals↗

Central serotoninergic stimulation by fenfluramine challenge does not affect plasma thyrotropin-stimulating hormone levels in man.

Thyrotropin-stimulating hormone (TSH) and prolactin (PRL) responses to an acute oral challenge of fenfluramine (60 mg), a central serotoninergic (5-hydroxytryptamine) releasing/uptake inhibiting agent, were examined in 8 healthy males in order to assess the role of central serotoninergic stimulation in the release of TSH. Plasma PRL, but not TSH, was significantly elevated by fenfluramine. These data suggest that central serotoninergic activity does not play an important role in the physiologic release of plasma TSH in man. Further, thyrotropin-releasing hormone is unlikely to be the PRL-releasing factor involved in the fenfluramine-induced stimulation of PRL.

Administration, Oral↗

Induction of fibroblast spreading by Mn2+: a possible role for unusual binding sites for divalent cations in receptors for proteins containing Arg-Gly-Asp.

Mn2+ at low (microM) concentrations fulfils the divalent cation requirement for spreading of BHK21 cells on fibronectin. At much higher concentrations, Mn2+ (and to a small extent also Mg2+) induces spreading on haemoglobin, not normally an adhesive protein. Since high Mn2+ also induces spreading of BHK variants unresponsive to exogenous fibronectin, it is unlikely to be acting as a cofactor for secreted cellular fibronectin or by stimulating its secretion. High Ca2+, but not Mg2+, inhibits the induction of spreading by Mn2+ on haemoglobin. Pre-treatment of cells with high concentrations of trypsin decreases the rate of spreading induced by Mg2+ on fibronectin, and by Mn2+ on haemoglobin, to similar extents. High and low Mn2+ could induce spreading, either by different mechanisms or through a common pathway. In the second case, at both concentrations, Mn2+ could act by binding to Ca2+/Mg2+ sites in one or more receptors for adhesion proteins. This would require binding of Mn2+ or Mg2+ to these sites to activate the receptors in the absence of adhesion proteins, and the effect of such proteins to be to increase the affinity of the sites for metal ions. The sites in question may be formed by sequences homologous to those found in the extracellular domains of the vitronectin receptor and platelet membrane glycoprotein IIb. Although very similar to the Ca2+-binding loop in the EF hand of calmodulin, these sequences more closely resemble bacterial galactose-binding protein in lacking one of the conserved co-ordinating side-chains.

Animals↗

Autonomic influences on heart rate and blood pressure in the toad, Bufo marinus, at rest and during exercise.

Blood pressure (PA) and heart rate (HR) were measured in the conscious, resting toad, Bufo marinus. Treatment with bretylium (an adrenergic neurone blocking agent), alone or in combination with phentolamine and propranolol (adrenoceptor antagonists) did not alter PA or HR significantly. Atropine caused a small but significant increase in HR but had no effect on PA. The experiments indicate a cholinergic cardio-inhibitory tone but give no evidence for an adrenergic pressor tone at rest. Treadmill exercise caused a rapid increase in PA and HR which was sustained throughout the exercise period. This response was partly psychogenic. The concentration of plasma catecholamines increased during exercise and was high enough to affect organs that were included in an extracorporeal blood circuit with the exercising animal. Bretylium treatment revealed an initial hypotension, presumably due to work hyperaemia, followed by a hypertension which was reduced compared to controls. The tachycardia was delayed but HR eventually reached control levels. Additional treatment with phentolamine and propranolol did not further affect the PA response, but significantly reduced the tachycardia reached during exercise. It is concluded that the cardiovascular responses to exercise involve adrenergic nerve fibres causing hypertension and an initial rapid tachycardia. Circulating catecholamines seem to be the major cause of the sustained tachycardia.

Animals↗

Dendritic growth and remodeling of cat retinal ganglion cells during fetal and postnatal development.

We have studied the development of retinal ganglion cell morphology in the cat's visual system from early fetal to postnatal times. In particular, we have examined the contribution of growth and remodeling to the establishment of mature retinal ganglion cell form. Ganglion cells were identified by retrograde labeling with rhodamine latex microspheres deposited in the superior colliculus and lateral geniculate nucleus between embryonic day 34 (E34; birth = E65) and adulthood. To reveal the fine morphological details of retrogradely labeled ganglion cells, 48 hr later Lucifer yellow was injected intracellularly in living retinae that had been dissected and maintained in vitro. Our results show that at E35-37 the majority of ganglion cells are very simple in morphology, with a few dendritic processes that are generally aligned in a radial direction towards or away from the optic disc. During the ensuing 2 week period, there is a progressive growth and elaboration of dendrites. By E50, some ganglion cells resembling the adult alpha, beta, and gamma classes can be identified based on comparisons of the appearance and dimensions of their dendritic trees and somata with neighboring filled cells. However, ganglion cell dendrites and axons at this age express several transient morphological features. The axons of ganglion cells give rise to delicate processes originating from the intraretinal portion of the axon, including side branches, present in about half of the cells, and occasionally bifurcations that give rise to axon collaterals. These transient axonal features are present throughout development, including the neonatal period; no axon collaterals were observed after postnatal day 15, while axonal side branches persisted even at P31 but were gone by adulthood. Ganglion cell dendrites exhibit excessive branches and exuberant somatic and dendritic spines. Quantitative analysis of these processes shows that after E45 dendritic trees increase dramatically in complexity, reaching the peak number of spines and branch points by the first week of postnatal life. The number of dendritic processes then falls abruptly to reach near-adult levels by the end of the first postnatal month. Even though dendritic morphology closely resembles that seen in the adult at this age, ganglion cell bodies and dendrites must continue to grow to reach their adult size.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Lack of evidence for the prognostic significance of c-erbB-2 amplification in human breast carcinoma.

Amplification of the c-erbB-2 proto-oncogene was detected in 10% of 122 primary human breast tumors examined. Examination of patients' histories with a post-surgical median follow-up time of 53 months suggested no statistically significant association between the increased copy number of c-erbB-2 proto-oncogene in breast tumors and several oncological disease parameters, such as histopathological grading, ovarian hormonal status, age, number of positive lymph nodes, time to relapse, and survival period. Results of the analysis of matched sets of primary tumors and lymph node metastases were also consistent with the lack of a strong association between increased copy number of c-erbB-2 proto-oncogene and aggressiveness of tumors.

Adult↗

Transient morphological features of identified ganglion cells in living fetal and neonatal retina.

The function and morphology of retinal ganglion cells in the adult mammalian visual system has been well studied, but little is known about how the adult state is achieved. To address this question, the morphological changes that retinal ganglion cells undergo during development were studied. Ganglion cells were first identified by retrograde labeling with rhodamine latex microspheres deposited in retinorecipient targets in fetal and early postnatal cats. The structure of ganglion cells was then revealed by intracellular injection of Lucifer yellow in living retinas removed and maintained in vitro. As early as 2 weeks before birth, a morphologically diverse assortment of ganglion cells is present, some of which resemble the alpha, beta, and gamma classes found in the adult. However, in contrast to the adult, developing ganglion cells exhibit several transient features, including excessive axonal and dendritic branching and exuberant somatic and dendritic spines. These morphological features indicate that there is a transient network of connectivity that could play an important role in the final determination of retinal ganglion cell form and function.

Animals↗