The affinity of hydroxystilbamidine for psoriatic lesions.
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Humans↗
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Treatment of systemic blastomycosis with 2-hydroxystilbamidine.
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Blastomycosis↗
Systemic blastomycosis treated with 2-hydroxystilbamidine.
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Blastomycosis↗
Experiences with 2-hydroxystilbamidine in systemic sporotrichosis; report of an unusual case.
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Hypersensitivity↗
Cryptococcal infection treated with 2-hydroxystilbamidine in a patient with Boeck's sarcoid.
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Cryptococcosis↗
Pulmonary blastomycosis in children. Amphotericin B therapy and a review.
Two children, aged 3 months and 4 years, respectively, were treated with ten weeks of amphotericin B for culture proved pulmonary blastomycosis. Organisms were easily demonstrated in nasopharyngeal or sputum specimens on admission. Although organisms were present until the 12th and 19th days of therapy, respectively, they were viable through only the seventh and 12th days of therapy. Both patients had thrombophlebitis, anemia, neutropenia, hypokalemia, fever, and vomiting develop during therapy. The less toxic drug hydroxystilbamidine isethionate, given for only 17 to 30 days, has been used successfully in at least six previously reported cases. Long courses of amphotericin B therapy may not be necessary for the treatment of pulmonary blastomycosis in selected children.
Amphotericin B↗
Ventral striatopallidothalamic projection: IV. Relative involvements of neurochemically distinct subterritories in the ventral pallidum and adjacent parts of the rostroventral forebrain.
Retrograde and anterograde tract-tracing studies were carried out to determine whether the capacity of the nucleus accumbens to influence the thalamic mediodorsal nucleus via ventral striatopallidothalamic connections disproportionately favors the shell over the core subterritory. After injections of Fluoro-Gold into the mediodorsal thalamic nucleus, retrogradely labeled neurons were detected in sections also processed for calbindin-D 28-kD and neurotensin immunoreactivities to facilitate identification of subterritories in the ventral pallidum. Fluoro-Gold-labeled cells were counted in series of sections cut through the ventral pallidum, rostral globus pallidus, nucleus of the vertical limb of the diagonal band, preoptic region, lateral hypothalamus, and the sublenticular gray region, including parts of the extended amygdala. Data were expressed as cells/unit area and as percentages of all labeled forebrain cells. Mediodorsal nucleus-projecting rostroventral forebrain neurons were most numerous in the ventromedial part of the subcommissural ventral pallidum and pallidal parts of the olfactory tubercle. Few were observed in the dorsolateral part of the subcommissural ventral pallidum. In addition, following injections into the ventral pallidum, anterogradely transported biotinylated dextran amine was evaluated in sections processed for calbindin or tyrosine hydroxylase immunoreactivities. Injection into the ventromedial part of the subcommissural ventral pallidum resulted in robust anterograde labeling of the medial segment of the mediodorsal nucleus and ventral tegmental area and weak labeling of the substantia nigra and subthalamic nucleus. Conversely, after injection into the dorsolateral part of the subcommissural ventral pallidum, anterograde labeling was weak in the mediodorsal nucleus and ventral tegmental area, but robust in the substantia nigra and subthalamic nucleus. The results are consistent with a predominant accumbens shell influence on the mediodorsal nucleus and with cortico-ventral striatopallidal-thalamocortical pathways that begin and end in different parts of the frontal lobe.
Amines↗
Identification of cells that express 5-hydroxytryptamine1A receptors in the nervous systems of the bowel and pancreas.
Although serotonin (5-HT)1A receptors are known to be present on neural elements in both the bowel and the pancreas, the precise location of these receptors has not previously been determined. Earlier investigations have suggested that 5-HT1A receptors are synthesized in enteric, but not pancreatic ganglia, and that they mediate pre-and postjunctional inhibition. Wholemount in situ hybridization was used to identify cells that contain mRNA encoding 5-HT1A receptors, and immunocytochemistry was employed to locate receptor protein. mRNA encoding 5-HT1A receptors was found in the majority of neurons in both submucosal and myenteric plexuses. 5-HT1A immunoreactivity, however, was abundant only on the surfaces of a limited subset of nerve cell bodies and processes. 5-HT-immunoreactive axons were found in close proximity to sites of 5-HT1A immunoreactivity. Myenteric, but not submucosal calbindin-immunoreactive neurons (with Dogiel type II morphology) were surrounded by rings of 5-HT1A immunoreactivity. The cytoplasm of the cell bodies and dendrites of a small subset of Dogiel type I neurons was also intensely 5-HT1A immunoreactive. Most of the Dogiel type I 5-HT1A-immunoreactive myenteric neurons, and some of the type II neurons that were ringed by 5-HT1A immunoreactivity became doubly labeled following injections of the retrograde tracer, FluoroGold (FG), into the submucosal plexus. 5-HT1A-immunoreactive neurons in distant submucosal ganglia also became labeled by retrograde transport of FG. None of the 5-HT1A-immunoreactive cells were labeled by the intraluminal administration of the beta-subunit of cholera toxin, a marker for vasoactive intestinal peptide-containing secretomotor neurons. These observations suggest that some of the myenteric 5-HT1A-immunoreactive neurons project to submucosal ganglia and that the submucosal 5-HT1A-immunoreactive cells are interneurons. In addition to neurons, a subset of 5-HT-containing enterochromaffin cells expressed 5-HT1A immunoreactivity, which was co-localized with 5-HT in secretory granules. In the pancreas, 5-HT1A immunoreactivity was observed in ganglia, acinar nerves, and glucagonimmunoreactive islet cells. Serotonergic enteropancreatic axons have been found to terminate in close proximity to each of these structures, which may thus be the targets of this innervation. The abundance of 5-HT1A receptor immunoreactivity on nerves of the gut and pancreas suggests that drugs designed to interact with these receptors may have unanticipated visceral actions.
Animals↗
Fos expression in forebrain afferents to the hypothalamic paraventricular nucleus following swim stress.
The paraventricular nucleus of the hypothalamus (PVN) serves as the origin of the final common pathway in the secretion of glucocorticoid hormones in response to stress. Various stress-related inputs converge upon the cells of the medial parvocellular division of the PVN. These neurons, which synthesize and release corticotropin-releasing hormone, arginine vasopressin, and other secretagogues, are responsible for a cascade of events which culminates in the adrenocorticotropin-induced release of corticosteroids from the adrenal cortex. Previous data have suggested complex afferent regulation of PVN neurons, although the neuronal pathways by which the effects of stress are mediated remain to be fully disclosed. The present experiment sought to identify forebrain areas potentially involved in afferent regulation of the PVN in response to an acute stressor. Discrete injections of the retrograde tracer Fluoro-gold were delivered to the PVN, and rats were subsequently subjected to an acute swim stress. Brains were processed immunocytochemically for the simultaneous detection of the tracer and Fos, the protein product of the immediate early gene c-fos, utilized as a marker for neuronal activation. The majority of Fluoro-gold/Fos labeled neurons were detected in the parastrial nucleus, the medial preoptic area, the anterior hypothalamic area, the dorsomedial hypothalamic nucleus and adjacent posterior hypothalamic area, and, to a lesser extent, the supramammillary nucleus. These findings are discussed in relation to neural pathways mediating activation and inhibition of the hypothalamic-pituitary-adrenocortical axis.
Afferent Pathways↗
Projection of the nucleus pretectalis to a retinorecipient tectal layer in the pigeon (Columba livia).
The avian optic tectum is composed of at least 15 separate laminae that are distinguishable on the basis of their morphological features and patterns of afferent and efferent connectivity. Layer 5b, a major retinorecipient layer, exhibits dense, dust-like, neuropeptide Y-positive (NPY+) immunoreactive labeling, whereas sparse, larger caliber NPY+ fibers are found in laminae 4 and 7. Anterograde and retrograde labeling techniques, immunohistochemistry, and retinal lesion studies were used to determine the source of this tectal NPY+ labeling. NPY+ was not detectable in cells of the optic tectum or in retinal ganglion cells, and retinal ablation did not diminish the abundance of tectal NPY+ fibers. Neurons of two nuclei previously shown to be sources of tectal input, the nucleus pretectalis (PT) and the intergeniculate leaflet (IGL; Brecha, 1978), were found to be NPY+. Unilateral injection of retrograde tracers into the tectum resulted in bilateral labeling of neurons within PT, and injections of anterograde tracer into PT confirmed that this nucleus projected bilaterally to layer 5b of the optic tectum. Unilateral lesions of PT nearly eliminated NPY+ fibers in the ipsilateral layer 5b and significantly reduced them in the contralateral layer 5b. Bilateral lesions of PT eliminated NPY+ fibers bilaterally in layer 5b. However, these PT lesions had little effect on the NPY+ fibers in layers 4 and 7. Combined retrograde and immunohistochemical studies showed that NPY+ neurons of the IGL project to the optic tectum, and anterograde studies demonstrated that IGL projects to layers 4 and 7. The NPY+ projection to laminae 5b from PT is one of many inputs, which include cholinergic afferents from the nucleus isthmi parvicellularis, terminals from retinal ganglion cells, and dendrites of layer 13 neurons (Karten et al., 1993). The NPY+ input to layer 5b may modulate visual information flow from retinal input to various tectal neurons, including those in layer 13.
Animals↗
Distribution of bombesin-like immunoreactivity in the nucleus of the solitary tract and dorsal motor nucleus of the rat and human: colocalization with tyrosine hydroxylase.
Bombesin is a peptide neurotransmitter/neuromodulator with important autonomic and behavioral effects that are mediated, at least in part, by bombesin-containing neurons and nerve terminals in the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (DMV). The distribution of bombesin-like immunoreactive nerve terminals/fibers and cell bodies in relation to a viscerotopically relevant subnuclear map of this region was studied by using an immunoperoxidase technique. In the rat, bombesin fiber/terminal staining was heavy in an area that included the medial subnucleus of the NTS and the DMV over their full rostral-caudal extent. Distinctly void of staining were the gelatinous, central, and rostral commissural subnuclei and the periventricular area of the NTS, regions to which gastric, esophageal, cecal, and colonic primary afferents preferentially project. The caudal commissural and dorsal subnuclei had light bombesin fiber/terminal staining, as did the intermediate, interstitial, ventral, and ventrolateral subnuclei. With colchicine pretreatment, numerous cell bodies were stained in the medial and dorsal subnuclei, with fewer neurons in the caudal commissural, intermediate, interstitial, ventral, and ventrolateral subnuclei. Bombesin-like immunoreactive neurons were found in numerous other areas of the brain, including the ventrolateral medulla, the parabrachial nucleus, and the medial geniculate body. In the human NTS/DMV complex, the distribution of bombesin fiber/terminal staining was very similar to the rat. In addition, occasional bombesin-like immunoreactive neurons were labeled in a number of subnuclei, with clusters of neurons labeled in the dorsal and ventrolateral subnuclei. Double immunofluorescence studies in rat demonstrated that bombesin colocalizes with tyrosine hydroxylase in neurons in the dorsal subnucleus of the NTS. Bombesin does not colocalize with tyrosine hydroxylase in any other location in the brain. In conclusion, the distribution of bombesin in the NTS adheres to a viscerotopically relevant map. This is the anatomical substrate for the effects of bombesin on gastrointestinal function and satiety and its likely role in concluding a meal. The anatomic similarities between human and rat suggest that bombesin has similar functions in the visceral neuraxis of these two species. Bombesin coexists with catecholamines in neurons in the dorsal subnucleus, which likely mediate, in part, the cardiovascular effects of bombesin.
Adult↗
Induction of NADPH-diaphorase/nitric oxide synthase in the brainstem trigeminal system resulting from cerebellar lesions.
Recent evidence indicates that NADPH-diaphorase (NADPH-d) and nitric oxide synthase (NOS) can be induced in cerebellar afferent neurons following mechanical, thermal, or chemical damage to the cerebellar cortex (Saxon and Beitz [1994] Neuroreport 5:809-812). The present study reports on the induction of NADPH-d/NOS in neurons of the brainstem trigeminal complex (BVC). Three groups of rats were used: Group I received a unilateral glass micropipette lesion into the vermal/paravermal region of the cerebellar cortex, group II received a concurrent injection of fluoro-gold along with the pipette lesion, and in group III the cerebellar cortex on one side was aspirated. Following survival times of 7-120 days, animals were processed for NADPH-d histochemistry. All three groups showed projection-specific induction of NADPH-d in different regions of the brainstem trigeminal complex. Induced neurons were distributed throughout the ipsilateral subnucleus interpolaris, principal trigeminal nucleus, and intertrigeminal nucleus. Subnucleus oralis contained a small number of induced neurons localized to the ipsilateral dorsomedial portion of the subnucleus. Projection-specific induction was confirmed by the presence of neurons double-labeled for NADPH-d and Fluoro-Gold. Although the functional consequences of NADPH-d/NOS induction remain to be elucidated, the induction of these enzymes in precerebellar neurons suggests that nitric oxide may play a role in the neuronal response to target specific lesions.
Animals↗
Neurogenesis of subpopulations of rat lumbar dorsal root ganglion neurons including neurons projecting to the dorsal column nuclei.
The time of birth of subpopulations of dorsal root ganglion (DRG) neurons was studied with immunohistochemistry for 5-bromodeoxyuridine (BrdU). Pregnant rats were injected with BrdU i.p. to label the neurons on one of the embryonic days (E) E11-E16. When they were adults, the rats were given injections of Fluoro-Gold (FG) into the gracile nucleus to identify DRG neurons projecting to this structure. Following a 5 day survival period, the animals were perfused with aldehyde fixative. Sections from the L3-L5 DRGs were processed for BrdU immunohistochemistry followed by either immunostaining for the antineurofilament antibody RT97, as marker of the light neuronal subpopulation, or histochemical staining for the B4 isolectin from Griffonia simplicifolia I, as marker of the small dark subpopulation. The results indicated that the DRG neurons were generated between E12 and E16. The RT97+ neurons were generated on E12-E15, with a peak at E13. FG+ neurons, the majority of which were RT97+, were also generated on E12-E15. The B4+ neurons were generated on E13-E16, with a peak around E14. The overall pattern of neurogenesis of the DRG neurons showed that the RT97+ neurons were produced prior to the B4+ neurons. These findings are in agreement with earlier observations that the large DRG neurons are generated earlier than the small dark neurons. Our findings also suggest the existence of a third neuronal subpopulation that might be produced at the latest period of DRG neurogenesis at E15-E16.
Animals↗
Efferent connections of the caudal part of the globus pallidus in the rat.
The efferent connections of the caudal pole of the globus pallidus (GP) were examined in the rat by employing the anterograde axonal transport of Phaseolus vulgaris leucoagglutinin (PHA-L), and the retrograde transport of fluorescent tracers combined with choline acetyltransferase (ChAT) or parvalbumin (PV) immunofluorescence histochemistry. Labeled fibers from the caudal GP distribute to the caudate-putamen, nucleus of the ansa lenticularis, reuniens, reticular thalamic nucleus (mainly its posterior extent), and along a thin strip of the zona incerta adjacent to the cerebral peduncle. The entopeduncular and subthalamic nuclei do not appear to receive input from the caudal GP. Descending fibers from the caudal GP course in the cerebral peduncle and project to posterior thalamic nuclei (the subparafascicular and suprageniculate nuclei, medial division of the medial geniculate nucleus, and posterior intralaminar nucleus/peripeduncular area) and to extensive brainstem territories, including the pars lateralis of the substantia nigra, lateral terminal nucleus of the accessory optic system, nucleus of the brachium of the inferior colliculus, nucleus sagulum, external cortical nucleus of the inferior colliculus, cuneiform nucleus, and periaqueductal gray. In cases with deposits of PHA-L in the ventral part of the caudal GP, labeled fibers in addition distribute to the lateral amygdaloid nucleus, amygdalostriatal transition area, cerebral cortex (mainly perirhinal, temporal, and somatosensory areas) and rostroventral part of the lateral hypothalamus. Following injections of fluorescent tracer centered in the lateral hypothalamus, posterior intralaminar nucleus, substantia nigra, pars lateralis, or lateral terminal nucleus, a substantial number of retrogradely labeled cells is observed in the caudal GP. None of these cells express ChAT immunoreactivity, but, except for the ones projecting to the lateral hypothalamus, a significant proportion is immunoreactive to PV. Our results indicate that caudal GP efferents differ from those of the rostral GP in that they project to extensive brainstem territories and appear to be less intimately related to intrinsic basal ganglia circuits. Moreover, our data suggest a possible participation of the caudal GP in feedback loops involving posterior cortical areas, posterior striatopallidal districts, and posterior thalamic nuclei. Taken as a whole, the projections of the caudal GP suggest a potential role of this pallidal district in visuomotor and auditory processes.
Amidines↗
Calretinin in the thalamic reticular nucleus of the rat: distribution and relationship with ipsilateral and contralateral efferents.
In order to investigate the existence of anatomical subdivisions within the thalamic reticular nucleus (Rt), the distribution of reticular neurons expressing the calcium binding protein calretinin was investigated in the rat by means of immunocytochemistry. Calretinin immunoreactive (Cr-ir) neurons were mainly distributed in the lateral and ventral regions, and along the medial border of the Rt rostral pole. Caudal to the rostral pole, many neurons were Cr-ir in the more dorsal part of the rostral two-thirds (the "dorsal cap") of the Rt. Fewer Cr-ir neurons were present more caudally along the lateral and medial borders, and in the caudalmost part of the nucleus, related to the acoustic thalamus. The distribution of Cr-ir neurons in the rostral Rt was compared with that of neurons projecting to the ipsilateral and contralateral anterior, intralaminar, midline, and mediodorsal nuclei, or to the contralateral rostral Rt. The retrograde transport of Fluorogold revealed a remarkably precise topography of the rostral Rt: different reticular areas were found to project to different thalamic nuclei, or to different rostrocaudal or mediolateral portions of the same thalamic nucleus, with a limited degree of overlap. The double-labeling experiments demonstrated that the reticular neurons projecting to the ipsilateral anterodorsal, midline, mediodorsal, and anterior intralaminar nuclei frequently expressed calretinin; by contrast, the majority of the reticular commissural neurons did not express the protein, with the exception of neurons projecting to the contralateral mediodorsal and midline nuclei. The ipsilaterally projecting calretinin-positive neurons were frequently located along the medial edge of the rostral pole and in the dorsal cap of the nucleus, segregated from the commissural calretinin-negative neurons. The combined analysis of calretinin expression patterns and tract tracing data provided further insight in the anatomical organization of the thalamic reticular nucleus, suggesting a different neurophysiological role for the ipsilaterally vs. the contralaterally projecting reticular neurons in the modulation of the synaptic activity of the dorsal thalamus.
Animals↗
Relationship of NK3 receptor-immunoreactivity to subpopulations of neurons in rat spinal cord.
The distribution of immunoreactivity to the neurokinin3 receptor (NK3R) was examined in segments C7, T11-12, L1-2, and L4-6 of the rat spinal cord. NK3R immunoreactivity was visualized by using two antisera generated against sequences of amino acids contained in the C-terminal region of the NK3R. NK3R-immunoreactive cells were numerous in the substantia gelatinosa of all spinal segments examined as well as the dorsal commissural nucleus of spinal segments L1-2. Isolated, immunoreactive cells were scattered throughout other regions of the spinal cord. The relationship of NK3R-immunoreactivity with neurons was demonstrated by colocalization with microtubule associated protein 2-immunoreactivity in individual cells. Within neurons, NK3R-immunoreactivity was associated predominately with the plasma membrane of cell bodies and dendrites. Within the substantia gelatinosa, 86% of nitric oxide synthase (NOS)-immunoreactive neurons were also NK3R-immunoreactive. Although NOS-immunoreactive neurons were found throughout all other regions of the spinal cord in the segments examined, these were not NK3R-immunoreactive. When preganglionic sympathetic neurons in spinal segments T11-12 and L1-2 were visualized by intraperitoneal injection of Fluorogold, less than 1% of the Fluorogold-labeled neurons were also immunoreactive for NK3R. The large number of NK3R-immunoreactive neurons in the substantia gelatinosa suggests that some effects of tachykinins on somatosensation may be mediated by NK3R.
Animals↗
Organization of neural inputs to the suprachiasmatic nucleus in the rat.
The circadian timing of the suprachiasmatic nucleus (SCN) is modulated by its neural inputs. In the present study, we examine the organization of the neural inputs to the rat SCN using both retrograde and anterograde tracing methods. After Fluoro-Gold injections into the SCN, retrogradely labeled neurons are present in a number of brain areas, including the infralimbic cortex, the lateral septum, the medial preoptic area, the subfornical organ, the paraventricular thalamus, the subparaventricular zone, the ventromedial hypothalamic nucleus, the posterior hypothalamic area, the intergeniculate leaflet, the olivary pretectal nucleus, the ventral subiculum, and the median raphe nuclei. In the anterograde tracing experiments, we observe three patterns of afferent termination within the SCN that correspond to the photic/raphe, limbic/hypothalamic, and thalamic inputs. The median raphe projection to the SCN terminates densely within the ventral subdivision and sparsely within the dorsal subdivision. Similarly, areas that receive photic input, such as the retina, the intergeniculate leaflet, and the pretectal area, densely innervate the ventral SCN but provide only minor innervation of the dorsal SCN. A complementary pattern of axonal labeling, with labeled fibers concentrated in the dorsal SCN, is observed after anterograde tracer injections into the hypothalamus and into limbic areas, such as the ventral subiculum and infralimbic cortex. A third, less common pattern of labeling, exemplified by the paraventricular thalamic afferents, consists of diffuse axonal labeling throughout the SCN. Our results show that the SCN afferent connections are topographically organized. These hodological differences may reflect a functional heterogeneity within the SCN.
Afferent Pathways↗
The region of the pontine parabrachial nucleus is a major target of dehydration-sensitive CRH neurons in the rat lateral hypothalamic area.
Neurons in a restricted part of the lateral hypothalamic area (LHA) show increased expression of corticotropin-releasing hormone (CRH) mRNA as a consequence of cellular dehydration. In the present study, we have investigated the organization of their efferent projections by using anterograde and retrograde tracing techniques. Additionally, we have compared the distribution of CRH mRNA-containing neurons after cellular dehydration and intraventricular (i.c.v.) colchicine injections. Our results show that cellular dehydration activates a more restricted neuronal population than does i.c.v. colchicine. Iontophoretic injections of Phaseolus vulgaris leucoagglutinin (PHAL) were placed in the LHA of animals drinking hypertonic saline and their proximity to activated CRH neurons determined by in situ hybridization for CRH mRNA. Although labelled fibers from these injections were seen throughout the brain, the region of the parabrachial nucleus and nucleus of the solitary tract (NTS) were most conspicuous in also having CRH immunoreactive fibers. Injections of Fluoro-Gold placed in these two structures were used to confirm these findings in dehydrated animals. Significant numbers of neurons containing both Fluoro-Gold and CRH mRNA were seen in the lateral hypothalamus after injections in the lateral and medial parts of the parabrachial nucleus; far fewer were seen after injections in the NTS. These results strongly suggest that the CRH neurons in the LHA activated by cellular dehydration provide an input to the region of the parabrachial nucleus. The altered biochemical composition of this pathway may well be able to modify sensory and motor patterns both during and after dehydration.
Animals↗