Participation of c-myc protein in DNA synthesis of human cells.

The protein product of oncogene c-myc is believed to be important in regulation of the cell cycle. However, its direct role in DNA synthesis has not been explored. Experiments presented here show that the addition of affinity-purified antibodies against the human c-myc protein to nuclei isolated from several types of human cells reversibly inhibited DNA synthesis and DNA polymerase activity of these nuclei. This suggests that c-myc encodes a protein that is functionally involved in DNA synthesis.

Vitamin D-dependent calcium-binding protein in rat brain: biochemical and immunocytochemical characterization.

Immunoreactive calcium-binding protein (CaBP) has been characterized in rat brain both biochemically and immunocytochemically. In this study antiserum to chick CaBP was used to characterize this protein and to describe its distribution in neurons and fibers of the rat fore- and midbrain. Immunostaining in neuronal elements was judged specific for this protein by the absence of staining in tissue sections after adsorption of the antiserum with either chick intestinal CaBP or the 28,000-dalton fraction from rat brain, but not with other molecular weight fractions with calcium-binding activity. Immunoreactive CaBP was found to have a widespread distribution throughout the central nervous system, and was present in most but not all major neuronal cell groups and fiber tracts. The protein was limited primarily to neuronal elements and some ependymal cells, and was absent in glia and blood vessels. The proportion of immunoreactivity in neuronal perikarya and fibers varied among nuclei and within a given structure at different rostral-caudal levels. Immunoreactivity was prominent in neocortex, hippocampal formation (primarily in CA1 and granular cells of the dentate gyrus), hypothalamus, and amygdala. These areas are responsible for the regulation of a variety of pituitary hormones, and several bind steroids. Immunoreactive CaBP was also a major constituent of nonlimbic system pathways. The widespread distribution of immunoreactive CaBP in the central nervous system suggests that CaBP and the vitamin D endocrine system may play a significant role in the regulation of mammalian brain function.

Distribution of immunoreactive somatostatin (ISRIF) in the nervous system of the squid, Loligo pealei.

Somatostatin (SRIF) is a neuropeptide with a widespread distribution in the mammalian CNS. In the present study we have examined the distribution of immunoreactive-like SRIF (ISRIF)-containing elements in the nervous system of the cephalopod mollusk Loligo pealei, or the Woods Hole squid. ISRIF was localized by light immunocytochemistry in sections of the squid-optic lobe, circumesophageal ganglia-and in stellate ganglion. In the optic lobe, ISRIF neurons were found in the internal granule cell layer and medulla and immunoreactive fibers were seen throughout the lobe and in the optic tract but were absent from the optic nerve, i.e., the projection between the retina and optic lobe. In the supraesophageal complex, ISRIF neurons were found in all lobes, but primarily in the vertical, subvertical, and frontal. In the subesophageal ganglion, ISRIF neurons were seen mainly following unilateral pallial nerve lesions; these neurons were primarily small-to-medium sized. ISRIF fibers were seen in many of the nerves exiting from the brain and in nerves extending between the sub- and supra-esophageal ganglia. In the stellate ganglion, ISRIF was present in many neurons as well as in a plexus of fibers within the ganglion; the peptide was absent from the second-order fibers and the giant axon. The data suggest that a molecule immunologically similar to vertebrate SRIF may be a major transmitter/modulator in this invertebrate. These results provide a foundation for further studies to evaluate the role of this molecule.

Somatostatin (SRIF)-like immunoreactivity in subcortical and cortical visual centers of the rat.

The distribution of neuronal elements containing immunoreactive somatostatin (I-SRIF) in the rat central visual pathway was examined by light-microscopic immunocytochemistry. These studies were concerned with the location and morphology of neurons and innervated cells and the distribution of fiber and terminal plexuses in the primary visual cortex (area 17), visual association areas 18 and 18a, the superior colliculus, the lateral geniculate nucleus, and the pretectum. In the superior colliculus, I-SRIF-containing fibers and perikarya were distributed predominantly in the superficial, or visual, layers; these elements were moderately dense and occupied the entire mediolateral extent of these layers. In the intermediate and deep layers, immunoreactive neurons were widely scattered, and fibers were located mainly in the medial third. Immunoreactive cell populations in the superior colliculus included small bipolar neurons with fusiform perikarya and multipolar neurons with round to ovoid perikarya. In the pretectum, the peptide was demonstrable in large and small multipolar neurons of the nucleus of the optic tract and in the posterior and olivary pretectal nuclei. I-SRIF-containing neurons were also present in the nucleus of the posterior commissure, the nucleus of Edinger-Westphal, and the ventral division of the lateral geniculate nucleus. In the visual cortex, the peptide was present in all layers and in a variety of morphologically defined cell populations, including some which are presumed excitatory (pyramidal and bipolar cells) and others which are presumed inhibitory (bitufted and stellate cells). Our data suggest that somatostatin is involved in visual and visuomotor reflex pathways and in the horizontal optokinetic nystagmus reflex pathway. These results provide a foundation for further studies to evaluate the role of this peptide in visual processes.

Localization of neurons containing immunoreactive delta sleep-inducing peptide in the rat brain: an immunocytochemical study.

Delta sleep-inducing peptide has been found in the peripheral circulation of animals entering slow-wave, or delta, sleep. An antiserum to this peptide was used to localize immunoreactive-like delta sleep-inducing peptide in the rat brain. The peptide was shown to have a rather widespread distribution. In the forebrain, the majority of these neurons were found to extend in a continuous rostral-caudal band in the ventral one-third of the brain from the primary olfactory cortex to the lateral hypothalamus. Neurons were also present in the basal ganglia, amygdala, septum, and thalamus. In the brainstem, the neurons were widespread and associated with the reticular formation, raphe nuclei, nuclei of the trigeminal complex, several auditory nuclei--nuclei of the lateral lemniscus, cochlear nuclei, and inferior colliculus--, cerebellum, locus ceruleus, periventricular gray, and vagal and hypoglossal nuclei. Immunoreactive fibers were, in general, difficult to demonstrate; they were seen mainly in the vicinity of the third ventricle and near blood vessels. The function of delta sleep-inducing peptide is unknown and its role in sleep is still under investigation. The distribution of delta sleep-inducing peptide in the present study suggests that the peptide is a component of several systems--arousal, locomotion, auditory, visual and sensory--both somatic and vestibular. The widespread distribution of the peptide, the lack of demonstrable immunoreactive fiber tracts, and the presence of these neurons in areas known to contain aminergic and peptidergic neurons, raises the possibility that neurons containing delta sleep-inducing peptide may exert their effect by projecting directly into blood vessels and/or interacting with neurons in their immediate vicinity.

The somatostatin systems of the guinea-pig brainstem.

The tetradecapeptide somatostatin has been shown to have a widespread distribution in the rat brain. Except for its role in the inhibition of growth hormone secretion, the function of this molecule in the remainder of the central nervous system is unknown. To address this problem, the distribution of somatostatin-like immunoreactivity in the guinea-pig brainstem was examined systematically. Of 116 nuclei and/or areas, 34 nuclei had somatostatin neurons, 32 did not have any immunoreactivity and the remainder had immunoreactive fibers and/or terminals. Cranial nerve motor nuclei--somatic, branchiomeric and visceral--did not contain somatostatin neurons; somatostatin fibers were present in all nuclei with the exception of the somatic motor nuclei which innervate the ocular muscles. Of the cranial nerve sensory nuclei--both somatic and visceral--somatostatin neurons were present only in the somatic nuclei nervi spinal trigeminal caudalis, interpolaris and oralis; all of these nuclei, however, contained substantial numbers of immunoreactive fibers. Somatostatin neurons and fibers were also present in the spinal somatic sensory nuclei cuneatus medialis and gracilis. Of the cranial nerve special somatic sensory nuclei, somatostatin neurons were present in two vestibular nuclei--spinalis and medialis--and in the ventral cochlear nucleus. Not all of these nuclei contained somatostatin fibers. Of the nuclei related to the auditory system, somatostatin neurons were present only in the dorsal and ventral trapezoid nuclei and in the cortex of the inferior colliculus. In nuclei of the visual system in the brainstem, somatostatin neurons were present only in the superior colliculus. Of the raphe nuclei, four had somatostatin neurons--magnus, obscurus, pallidus and superior centralis; somatostatin fibers were present in all raphe nuclei. Of 24 nuclei in the reticular formation, 12 had somatostatin neurons--most notably nuclei gigantocellularis and paragigantocellularis--and only two nuclei, paranigralis and sagulum, did not contain any immunoreactive fibers. In the cerebellum, somatostatin fibers and terminals were restricted to the deep cerebellar nuclei. Of the 11 nuclei projecting to the cerebellum, five contained somatostatin neurons and the majority received somatostatin fibers. Of the limbic system nuclei, somatostatin neurons were confined to the central grey at both pontine and mesencephalic levels. Somatostatin neurons were present in the substantia nigra--compactus and lateralis, but not in reticularis--and absent from the nucleus ruber.(ABSTRACT TRUNCATED AT 400 WORDS)

The maturation of the somatostatin systems in the rat visual cortex.

The development of somatostatin-immunoreactive (SS) neurons and processes in the rat visual cortex (VC) was studied in animals from embryonic day 20 (E20) to postnatal day 21 (D21). Three distinct patterns of immunoreactivity were seen. From E20 to birth (D0), VC was characterized by a small number of mainly bipolar SS neurons throughout the cortical plate. In the perinatal period, from D1 to D6, there were large numbers of immature immunoreactive neurons which were confined to layer VI and the subplate zone, a few bipolar neurons in the cortical plate and an extremely dense plexus of SS processes throughout the neuropil. The third phase, from D8 to weaning, was characterized by the absence of immature SS neurons, an increase in the number of multipolar SS neurons and a decrease in the density of SS fibers. By D15, the time of eye-opening, the number and distribution of SS neurons and processes was close to that seen in the adult. These results indicate that the SS system of neurons and fibers is among the earliest of the transmitter systems to be established in VC and suggests a role for the peptide in cortical organization as well as visual processing.

Somatostatin-like immunoreactivity in the central visual pathway of the prenatal rat.

Somatostatin (SRIF)-like immunoreactivity was localized in the central visual pathway of near-term prenatal rats using light-microscopic immunocytochemistry and a highly specific antibody to the peptide. SRIF was demonstrable in neuronal perikarya and fibers of the lateral geniculate nucleus, superior colliculus and visual cortex. At this stage the distribution of these elements had not attained the pattern seen in the adult. The presence of SRIF in the central visual pathway prior to maturation suggests a role for this peptide in the development of visual function.

Serotonin metabolism and the nature of monoamine oxidase in squid central nervous system.

Monoamine oxidase activity, using type A and type B substrates and inhibitors, was investigated in the central brain and synaptosomes prepared from the optic lobe of squid. Although substantial MAO activity towards serotonin (5-HT), phenylethylamine and tyramine was present, the enzyme could not be differentiated into the two subtypes previously described in the vertebrate central nervous system. However, this enzyme is functional since 5-HT levels, as identified by immunocytochemical procedures, are low in the squid nervous system and show significant increases in pargyline treated squids.

The distribution of neurons containing delta sleep-inducing peptide in the hippocampal formation.

The distribution of neurons containing immunoreactive delta sleep-inducing peptide (IDSIP) in the hippocampal formation was investigated by immunocytochemistry. For this study, thirteen antisera to the peptide were used. Three antisera were found suitable for immunocytochemistry; the remainder gave only non-specific background staining. Neurons containing IDSIP were demonstrable in the subicular cortex immediately adjacent to CA1. No specific staining was found in other parts of the hippocampal formation including the pyramidal layer of Ammon's Horn and the dentate gyrus. These three antisera also stained cells in the cerebral cortex-primarily temporal, parietal and frontal regions--as well as in the ventral forebrain, although the number of cells in each area varied somewhat with the different antisera. The presence of IDSIP in neurons which constitute the major efferent pathway of the hippocampus, as well as in areas known to be functionally related to the hippocampus, i.e., the adjacent isocortices and ventral forebrain, suggests a possible role for the peptide in the regulation of behavior.

The blood oxygen level-dependent functional MR imaging signal can be used to identify brain tumors and distinguish them from normal tissue.

BACKGROUND AND PURPOSE: In neuro-oncology, a major problem is clear identification of tumor from the surrounding normal tissue. We hypothesized that we could use the blood oxygen level-dependent functional MR imaging (BOLD fMRI) signals from tumors and normal brain to identify the tumors and distinguish them from the surrounding brain. MATERIALS AND METHODS: Fourteen patients with meningiomas, gliomas, and metastatic tumors were scanned before surgery. All subjects performed a motor task; 2 subjects were also scanned while in a resting state. The BOLD signals were taken from selected points within the tumor and from the surrounding normal brain and were analyzed by using correlation analysis to determine how closely they were related. RESULTS: The BOLD signals from all of the tumors were significantly different from those in the surrounding normal tissue. In meningiomas and gliomas, selection of a voxel in the tumor for signal-intensity analysis highlighted the entire tumor mass while excluding the normal tissue. The BOLD signal intensity was the same whether the subjects were motionless or finger tapping. CONCLUSIONS: Analysis of the BOLD signal intensity provides a relatively simple and straightforward method for identifying brain tumors and distinguishing them from normal tissue. This approach may be of use in neurosurgery.

Catecholamine-containing neurons in cultures of fetal rat hypothalamus: distribution, morphology, and maturation.

The distribution, morphology, and maturation of catecholamine (CA) neurons have been studied in hypothalamic explants from late-gestation rats. CA-containing neurons were identified using the glyoxylic acid technique. CA-containing processes were present from all hypothalamic areas except the preoptic region. Several fiber types were identified. CA neurons in vitro resemble CA neurons in adult hypothalamus. This tissue culture system may be useful in the study of a number of properties of hypothalamus CA neurons.

The therapeutic use of ritual and ceremony in the treatment of post-traumatic stress disorder.

The therapeutic purposes and effects of specially designed ceremonies in the treatment of persons with post-traumatic stress disorder are described. Ceremonies compartmentalize the review of the trauma, provide symbolic enactments of transformation of previously shattered relationships, and reestablish connections among family and with society in general. Four ceremonies used with Vietnam combat veterans are described which focus on the themes of separation from and return to the family, forgiveness of the living, and releasing the dead. Ritual and ceremony are highly efficient vehicles for accessing and containing intense emotions evoked by traumatic experience. Evaluation by family and veterans judge these ceremonies to be the most effective components of treatment.

The concept of the Second Generation program in the treatment of post-traumatic stress disorder among Vietnam veterans.

The concepts of First and Second Generation treatment programs for Vietnam veterans with post-traumatic stress disorder are presented, based on a developmental theoretical model of adaptation. First Generation programs focus on accessing and then working through the effects of the war trauma and aim to diminish the intensity of core PTSD symptoms. Second Generation programs focus on reintegrating veterans into the social context of family and work, and aim to improve their ability to function in society. Both types of treatment may be required in order to help veterans resume their psychological and social development. The need to develop sophisticated models of comprehensive inpatient treatment in order to support scholarly discourse and outcome research is emphasized.

Antiviral properties of fucoidan fractions from Leathesia difformis.

Three fractions of fucoidans isolated from the brown seaweed Leathesia difformis (Ee, Ec and Ea) were found to be selective antiviral agents against herpes simplex virus (HSV) types 1 and 2 and human cytomegalovirus. Fraction Ea was the most active, with IC50 values in the range 0.5-1.9 microg/ml without affecting cell viability at concentrations up to 400 microg/ml. The antiherpetic activity of Ea was assessed by three different methods, plaque reduction, inhibition of virus yield and prevention of HSV-2 induced shut-off of cell protein synthesis, demonstrating that the inhibitory effect was independent of the antiviral assay and the multiplicity of infection. The mode of action of Ea could be ascribed to an inhibitory action on virus adsorption. The fucoidans did not inhibit the blood coagulation process even at concentrations exceeding more than 100 times the IC50 value.

Luteinizing hormone-releasing hormone (LH-RH) neurons in cultures of fetal rat hypothalamus.

Hypothalamic fragments from 21-day-old fetal rats were cultured in Maximow double-coverslip assemblies for 1 to 2 months. Neurons containing LH-RH were demonstrated immunohistochemically using an antiserum to LH-RH (Dermody; 1:500--1:4,000). LH-RH was demonstrable only in neuronal perikarya (8--13 micrometer) and in small (less than 1 micrometer) round structures nearby, primarily in explants of the median eminence-arcuate nucleus region. Reactive neurons were not found in explants of the preoptic area and could not be demonstrated in fetal hypothalami at the time of explantation. The presence of mature-looking LH-RH containing neurons in these cultures suggests that this tissue culture system can be used for the study of hypothalamic development.