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9452190 | Three-dimensional localization of dipoles for potentials evoked by posterior tibial nerve stimulation in the monkey. | Somatosensory evoked potentials (SEPs) elicited by right posterior tibial nerve stimulation were simultaneously recorded from 21-27 epidural electrodes in three monkeys. N23-P40 was recorded anterior to the left central sulcus, and P23-N40 was recorded on the parietal midline and the middle portion of the right hemisphere. These potentials were thought to be the primary cortical responses elicited by posterior tibial nerve stimulation in the monkey, since a topographical map made of them corresponded to the paradoxical lateralization of the primary ponents in human posterior tibial nerve SEPs. Current source generators (dipoles) of these potentials were 3-dimensionally identified dipoles located in the left side of the mesial wall of the anterior parietal cortex, and oriented obliquely toward the right hemisphere by a dipole tracing (DT) method in which the 3-dimensional localization of dipoles in the brain were estimated and superimposed on magnetic resonance imaging (MRI) images. |
9452191 | SCH 23390-induced behavioral supersensitivity is not related to striatal c-fos levels. | Stereotyped behavior and striatal c-fos levels induced by chronic treatment with the D1 dopamine antagonist SCH 23390 have been investigated in rats which received subsequent subacute dopamine agonist treatment. SCH 23390 treatment (0.5 mg/kg/day) for 21 days increased both apomorphine-induced orofacial stereotypies and striatal c-fos levels. Treatment with the D1 dopamine agonist SKF 38393 (10 mg/kg/day) and bination of SKF 38393 with the D2 dopamine agonist quinpirole (1 mg/kg/day), for 5 consecutive days, attenuated apomorphine-induced stereotypies without changing c-fos levels in rats previously treated with SCH 23390. These findings suggest that SCH 23390-induced behavioral supersensitivity and the increased striatal c-fos levels are itant but unrelated phenomena. |
9452192 | Changes in Ib heteronymous inhibition to soleus motoneurones during cutaneous and muscle nociceptive stimulation in humans. | The effects of selective tonic cutaneous and muscle pain stimulation on heteronymous Ib pathways from the gastrocnemius medialis to the soleus motoneurones were studied in five healthy human subjects. Tonic pain stimulation, monitored by a psychophysical method, was obtained by local injection of 60 mg levo-ascorbic acid (L-AS) in a volume of 0.3 ml. Nociceptive cutaneous and muscle stimulation of the dorsal foot produced opposite, long-lasting changes in heteronymous Ib pathways to soleus motoneurones: Ib facilitation during cutaneous stimulation was reversed by disinhibition during muscle stimulation. The time-course of these Ib changes strictly paralleled that of subjective pain sensation. On the contrary, when the same nociceptive stimuli were applied to the leg (at pretibial level), the differences between cutaneous and muscle pain disappeared and similar short-lasting phases of facilitation and inhibition of Ib activity were observed. It is concluded that tonic discharge of cutaneous and muscle nociceptive afferents arising from the foot have specific and opposite effects on Ib inhibitory pathways to ankle extensor motoneurones. These interactions between muscle and cutaneous nociceptive and Ib pathways may be used to change muscle synergies, thus contributing to the establishment of appropriate adaptive otor strategies during pain. |
9452193 | Intrinsic and extrinsic factors affecting phrenic motoneuronal excitability in neonatal rats. | We examined intrinsic and extrinsic factors affecting phrenic motoneuron (PMN) excitability in neonatal rats. Using an in vitro brainstem-spinal cord en bloc, 127 PMNs were recorded under whole-cell patch-clamp conditions. Inspiratory synaptic drives and passive membrane properties, including whole-cell membrane capacitance (Cm), input resistance (Rn), and time constant (tau), were measured with either voltage- or current-clamp techniques. On the basis of firing behavior during inspiration, two types of PMNs could be distinguished: active (107/127 = 84%) and silent PMNs (20/127 = 16%). Active PMNs always produced multiple spikes during inspiration, while silent PMNs remained silent for most inspiratory cycles. Compared to silent PMNs, active PMNs had significantly higher Rn, inspiratory drive potential, and more depolarized resting membrane potential (RMP). With respect to inspiratory drive current, no significant difference was observed between the two types of PMN. Analysis of action potential waveforms did not show a significant difference between their threshold levels. Our results suggest that in addition to size-related properties, RMP determines the recruitment of PMNs and consequently, of motor units in the diaphragm. |
9452194 | Alteration of protein kinase C activity after transient focal cerebral ischemia in mice using in vitro [3H]phorbol-12,13-dibutyrate binding autoradiography. | Changes in the regional distribution of protein kinase C (PKC) after transient focal cerebral ischemia in SV-129 mice were assessed by quantitative autoradiography using [3H]phorbol-12,13-dibutyrate ([3H]PDBu) binding. [3H]PDBu binding did not change up to 10 min after reperfusion of 3 h ischemia, but at 1 h after reperfusion markedly decreased to 40-50% of control (pre-ischemia) in the ipsilateral striatum and the middle cerebral artery (MCA) region of cortex in SV-129 mice. The binding decreased to 20% of control at 3-7 days after reperfusion, but did not change in the ipsilateral anterior cerebral artery (ACA) territory or the contralateral brain. In the ipsilateral substantia nigra, which lies outside the ischemic zone, [3H]PDBu binding was not significantly pared to the control values (pre-ischemia) at early phase (up to 3 h after reperfusion), but marked reduction of the binding was observed 1 day after reperfusion. After 3 h ischemia followed by 3 h reperfusion, the morphological damage and the decrease in [3H]PDBu binding in the ipsilateral striatum and the MCA region of cortex was smaller in mice lacking the expression of neuronal nitric oxide synthase (type I NOS) gene mutant pared to wild-type (SV-129 and C57black/6) mice. Our data suggest that postischemic alterations of PKC binding activity were observed in the ischemic and non-ischemic lesions in the mouse brain. |
9452195 | Sensory nociceptive axons invade the cerebellum of transgenic mice overexpressing nerve growth factor. | Transgenic mice possessing elevated levels of mRNA expression and synthesis for the neurotrophin nerve growth factor among astrocytes display a robust ingrowth of new sympathetic fibers to the cerebellum. In this investigation, we report that the cerebellum of these mice also possesses a dense plexus of aberrant axons of sensory origin. Axons stained immunohistochemically for calcitonin gene-related peptide were seen in the transgenic cerebellum as early as one week after birth. The density of these axons dramatically increased with age. Immunopositive axons were confined predominantly to the deep white matter of the cerebellum in the adult transgenic mice, with a smaller number of axons seen coursing along blood vessels in the gray matter. Axons stained immunohistochemically for the neurotrophin receptor, p75NTR, displayed a similar pattern of distribution and density as those immunostained for calcitonin gene-related peptide. Wild-type post-natal and adult animals lacked such calcitonin gene-related peptide- and p75NTR-immunoreactive axons in the cerebellum. Retrograde labelling revealed that these axons within the transgenic cerebellum originated from neurons in the sensory trigeminal and dorsal root ganglia (upper cervical levels). This investigation demonstrates that overexpression of nerve growth factor is capable of inducing the directional growth of collateral axons of sensory neurons into the undamaged mammalian central nervous system. |
9452196 | The novel compound TDN-345 induces synthesis/secretion of nerve growth factor in C6-10A glioma cells. | A pound, TDN-345, not bearing catechol moiety, induced NGF synthesis/secretion in C6-10A glioma cells. Both intracellular and extracellular nerve growth factor (NGF) protein levels increased within 3 h and reached a maximum around 12 h after the addition of TDN-345. The induction of NGF synthesis/secretion by TDN-345 occurred in a concentration-dependent manner, beginning with about 0.1 microM and reaching a maximum at 10 microM. The ED50 was 0.88 microM. The induction was panied by an increase in NGF mRNA but not beta-actin mRNA. In a time-course study, the NGF mRNA level was found to reach a maximum 2-3 h after the addition of TDN-345 and then to return to control levels. The induction occurred dose-dependently. The pound epinephrine, which induces NGF synthesis/secretion, increased the intracellular cyclic AMP content by more than 1000-times at 10 microM. In contrast, TDN-345 did not cause such a prominent increase in cAMP even at 100 microM. These results indicate that TDN-345 induces NGF synthesis/secretion by increasing NGF mRNA expression, and the action of TDN-345 clearly differs from that of epinephrine, as it does not seem to involve cAMP as a second messenger. The results of the present study suggest the existence of a signal transduction pathway for NGF synthesis/secretion which is not mediated by cAMP. |
9452197 | p-Chlorophenylalanine and fluoxetine inhibit D-fenfluramine-induced Fos expression in the paraventricular nucleus, cingulate cortex and frontal cortex but not in other forebrain and brainstem regions. | D-Fenfluramine, a putative serotonin releaser and reuptake inhibitor, monly prescribed for the treatment of obesity. Brain sites activated by D-fenfluramine have been mapped via the expression of the immediate early gene Fos. However, it is not clear that serotonin release in the brain mediates the effects of D-fenfluramine on Fos expression. The present study determined whether D-fenfluramine induces the expression of Fos in the brain through the release of serotonin. Rats were pretreated either with the serotonin depleting drug p-chlorophenylalanine (PCPA) or with the serotonin reuptake inhibitor fluoxetine. Both drugs inhibited D-fenfluramine-induced Fos expression in the cingulate cortex, frontal cortex, and the parvocellular subdivision of the paraventricular nucleus of the hypothalamus. Neither drug reduced D-fenfluramine-induced Fos responses in several other brain areas, including the caudate-putamen, amygdala, and brainstem regions such as the lateral parabrachial nucleus and nucleus of the solitary tract. These results indicate regional specificity of mechanisms mediating D-fenfluramine-induced Fos expression. It is likely that D-fenfluramine-induced Fos expression at various sites in the brain is mediated via bination of serotonin release and other, as yet unidentified, neurotransmitters. |
9452198 | Neurons of the posterior subdivision of the nucleus preopticus periventricularis project to the preglomerular nucleus in the weakly electric fish, Apteronotus leptorhynchus. | By using an in vitro tract-tracing technique, the neural connections between two diencephalic cell groups, the posterior subdivision of the nucleus preopticus periventricularis (PPp) and the preglomerular nucleus (PG), was examined in the weakly electric gymnotiform fish Apteronotus leptorhynchus. Neurons of the PPp project to one area within PG, the ventromedial cell group of the medial subdivision of the preglomerular nucleus (PGm-vmc). Axons of these cells reach the ipsilateral PGm-vmc via the basic hypothalamic tract, while collaterals decussate via the missure to innervate the contralateral PGm-vmc. We hypothesize that those neurons within PPp that project to the PGm-vmc are homologous to neurons of the medial preoptic area of mammals. As part of an elaborate circuit, PPp and PG may participate, as in mammals, in the control plex social behavior patterns. |
9452199 | Cyclic guanosine 3',5'-monophosphate-mediated neuroprotection by nitric oxide in dissociated cultures of rat dorsal root ganglion neurones. | In dissociated cultures of dorsal root ganglia (DRG) derived from 15-day-old rats, many neurones expressed nitric oxide synthase (NOS) and this expression was found to be reduced by nerve growth factor. The application of blockers of NOS caused selective death of those neurones expressing NOS. The soluble guanylate cyclase (sGC) blocker ODQ also caused neuronal death. The appearance of the neurones undergoing cell death was typical of apoptosis. This suggests that NO has a neuroprotective action in DRG neurones which is probably mediated by its activation of cyclic guanosine 3',5'-monophosphate. These observations are discussed in relation to the developmental and neuropathic changes in NOS expression by DRG neurones. |
9452200 | Changes in ouabain affinity of Na+, K+-ATPase during focal cerebral ischaemia in the mouse. | We investigated the effect of focal cerebral ischaemia on the activity and the affinity of the ouabain sites of Na+,K+-ATPase in the mouse. The Na+,K+-ATPase activity was decreased by 38% as early as 30 min following ischaemia. In the sham group, the dose-response curves for ouabain disclosed three inhibitory states which contribute, respectively, 24.9 +/- 6.7%, 39.1 +/- 7.5% and 36.0% of the total activity (low affinity, LA; high affinity, HA and very high affinity, VHA, respectively). puted IC50 values are, respectively: 1.3 X 10(-3) M, 4.5 X 10(-6) M and 2.9 X 10(-9) M. Surprisingly, in ischaemic cortices, only two sites for ouabain were detected. The first site exhibits a LA (IC50 = 2.0 X 10[-4] M) but its relative contribution to the total activity (46.1 +/- 5.2%) is twice that noted for the LA site in non-ischaemic tissues. The second site presents an affinity intermediate between those of HA and VHA sites of the sham group (IC50 = 1.7 X 10[-7] M) and contributes 53.9% to the total activity. Loss in the specific activity of the second site explains that of the total activity. The most likely explanation in the presence of only two ouabain sites of Na+,K+-ATPase following ischaemia may be a change in ouabain affinity of alpha2 and/or alpha3 isoforms, as the presence of all three alpha isoforms has been observed by Western blotting. These results suggest that ischaemia induces intrinsic modifications in Na+,K+-ATPase which result from perturbations in membrane integrity and/or association of the alpha isoforms of this enzyme. |
9452201 | Dexmedetomidine and halothane produce similar alterations in electroencephalographic and electromyographic activity in cats. | Dexmedetomidine, an alpha2-adrenergic agonist, produces sedation and reduces volatile anesthetic requirements. This pared the actions of dexmedetomidine and halothane on the processed EEG and on the electromyogram (EMG) which has not been previously described. Chronically instrumented cats were prepared with arterial and venous cannulae, quadriceps EMG electrodes and EEG electrodes in the lateral geniculate nucleus and over the frontal and occipital cortices. Hemodynamics, EEG and EMG were recorded in the conscious state and after randomly administered halothane or intravenous dexmedetomidine (on separate days). Blink and tail-clamp responses also assessed level of consciousness. Halothane resulted in unconsciousness and a lack of response to tail clamping, while dexmedetomidine produced profound sedation, with preservation of tail-clamp responses. Both agents similarly decreased (P < 0.05) the median power frequency from 9.5 +/- 0.9 to 5.7 +/- 0.4 Hz (2% halothane) and from 9.6 +/- 0.7 to 5.9 +/- 0.8 Hz (20 microg/kg dexmedetomidine), and 95% power frequency from 23.0 +/- 0.2 to 18.2 +/- 0.6 Hz (2% halothane) and from 23.0 +/- 0.2 to 19.1 +/- 0.8 Hz (20 microg/kg dexmedetomidine). Both agents increased the total spectral power and delta band power of the EEG and reduced integrated EMG activity. Halothane and dexmedetomidine produced differing effects on level of consciousness as assessed by response to tail clamping. The results suggest that conventional processing of EEG and EMG parameters are inadequate to assess anesthetic depth in the presence of alpha2-adrenergic agonists. |
9452202 | Odor exposure reveals non-uniform expression profiles of c-Jun protein in rat olfactory bulb neurons. | In the main olfactory bulb, neurons are arranged strategically in distinct layers among which translaminar synaptic transmission can be made from the superficial, sensory to the deep, output layers that account for the processing of olfactory information. To search for stimulus-transcription coupling thought to be operated differentially in several cell types, c-Jun expression was examined immunohistochemically in rat olfactory bulb following 30-min odor stimulation with acetic acid and 1-butanol. c-Jun was rapidly induced in neuronal cell nuclei belonging to periglomerular, tufted, mitral and granule cells. The disappearance of c-Jun, however, differed between each cell type. In the glomerular layer, the posed of c-Jun-expressing periglomerular cells were seen. Different odors led to labeling of different sets of glomeruli. The labeled periglomerular cells disappeared within 2 h. In all the deeper layers, however, a rather homogeneous label was noted for the tufted, mitral and granule cells present throughout the olfactory bulb, regardless of the difference in odor. In tufted and mitral cells, the c-Jun expression persisted for 4 days after odor stimulation. In the granule cell layer, numerous granule cells increased c-Jun immunoreactivity which lasted for 1 day following odor application. In control rats which were given clean air, the basal amount of c-Jun expression was seen confined to scattered granule cells. The results suggest that c-Jun is expressed in a variety of odorant-stimulated bulb neurons with a time course being dependent on cell type. |
9452203 | Opioid-induced release of neurotensin in the periaqueductal gray matter of freely moving rats. | The midbrain periaqueductal gray matter (PAG) is an important region for endogenous pain suppression. Nerve terminals containing opioid peptides and neurotensin (NT), as well as high densities of opioid- and NT-receptors, have been demonstrated in the ventromedial PAG. Local administration of opioids or NT in this region induces antinociception in experimental animals. In the present microdialysis study, the effect of opioids on the release of NT in the ventromedial PAG was investigated. Perfusion of the microdialysis probe with 10 microM morphine induced a significant increase (P < 0.05; n = 5) of the extracellular level of NT-like immunoreactivity (NT-LI), while perfusion with a 10-fold higher concentration of morphine had no significant effect on the NT-LI release in the PAG. Also perfusion of the dialysis probe with the mu-opioid receptor-specific agonist [D-Ala2-N-Me-Phe4-Gly5-ol]-enkephaline (DAGO) (1 or 100 microM) induced a significant (P < 0.05; n = 7-9) increase of the NT-LI level. The increase in NT-LI release in response to 1 microM DAGO was both calcium-dependent and naloxone-reversible. Since opioid agonists generally inhibit neuronal activity, an indirect mechanism, involving inhibition of tonically active inhibitory neurons, e.g. gamma-aminobutyric acid (GABA) neurons, could be of importance for the opioid induced release of NT. However, local administration in the PAG of the GABA(A) antagonist bicuculline (0.1-10 microM) or the GABA(A) agonist muscimol (1-100 microM) had no significant effect on the extracellular NT-LI level in the PAG, suggesting that GABAergic mechanisms are not involved in the opioid-induced release of NT-LI. In conclusion, the present data provide in vivo evidence that mu-opioid receptors mediate stimulation of neurotensin release in the PAG. |
9452204 | Short-latency synaptic patterns among cat peroneal motoneurons. | Motoneurons innervating peroneal muscles in the cat leg (PB, PT and PL, respectively, for peroneus brevis, tertius and longus) were examined for their connections with afferents from these and other leg muscles and with cutaneous afferents. The aim was to investigate (1) whether inputs from nearby muscles and cutaneous areas are likely to assist or oppose the excitation elicited in peroneal motoneurons by PB contractions, and (2) whether reflex connectivity might allow distinction of alpha (i.e. motoneurons innervating skeletal muscle fibres) and beta (i.e. motoneurons innervating both skeletal and intrafusal muscle fibres) subgroups among PB and PT motoneurons. In the three peroneal pools, every motoneuron had excitatory monosynaptic connections with Ia afferents from each of the three peroneal muscles, and nearly every motoneuron received di- or trisynaptic excitation from low-threshold cutaneous afferents in sural or superficial peroneal nerves. Inputs from these sources might facilitate the contraction-induced positive feedback. In contrast, the patterns of short-latency synaptic connections with group I afferents from pretibial flexor and post-tibial extensor muscles were heterogeneous among peroneal motoneurons but did not point to any specific beta pattern. |
9452206 | Immunocytochemical localization of AMPA receptors in the rat inferior colliculus. | Immunocytochemistry was used to study the distribution of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subtypes in the inferior colliculus (IC) of genetically epilepsy-prone rats (GEPR-9s) and normal Sprague-Dawley (SD) rats. The analysis was conducted using 3 antibodies specific for glutamate receptor subtypes, GluR 1, GluR 2/3, and GluR 4. Light microscopy showed that immunostaining of the IC was most dense with the GluR 2/3 antibody for both strains of animals. The amount of GluR 2/3 immunolabeling was similar for sound-stimulated GEPR-9s, seizure-naive GEPR-9s, and SD rats. The electron microscopy of GluR 2/3 in the IC revealed immunoreaction products associated with the postsynaptic densities of asymmetric synapses. The thin sections parable amounts of reaction product in dendrites or dendritic spines for both strains. Since the distribution and quantity of AMPA receptors in the IC of GEPR-9s and SD rats are similar, our results indicate that altered AMPA receptors are probably not the primary cause of seizure initiation in GEPR-9s. |
9452205 | WAY 100635, a 5-HT1A receptor antagonist, prevents the impairment of spatial learning caused by intrahippocampal administration of scopolamine or 7-chloro-kynurenic acid. | The effect of WAY 100635, a 5-HT1A receptor antagonist, on the impairment of spatial learning caused by intrahippocampal administration of scopolamine, a cholinergic muscarinic receptor antagonist, or 7-chloro-kynurenic acid, an antagonist at the glycine site associated with the NMDA plex, was studied in a two-platform spatial discrimination task. Scopolamine (4 microg/microl) or 7-chloro-kynurenic acid (3 microg/microl), administered bilaterally into the CA1 region of the dorsal hippocampus 10 min before each training session, impaired choice accuracy with no effect on choice latency and errors of omission. Administered subcutaneously at 1 (but not at 0.3) mg/kg 30 min before each training session, WAY 100635 did not modify the acquisition of spatial learning, but prevented the impairment of choice accuracy caused by intrahippocampal scopolamine or 7-chloro-kynurenic acid. These findings suggest that blockade of 5-HT1A receptors pensate the loss of cholinergic or NMDA-mediated excitatory input to pyramidal cells in the hippocampus. The mechanisms involved and the importance of these findings for the symptomatic treatment of memory disorders in man are discussed. |
9452207 | Tissue-specific mRNA expression of a calcitonin receptor-like receptor during fetal and postnatal development. | The distribution of calcitonin receptor-like receptor (CRLR) mRNA in developing rats was investigated by in situ hybridization. Signals were found in the piriform cortex, the central and basolateral amygdala and the amygdalostriatal transition area. Among peripheral organs, the CRLR was predominantly expressed in the lung. mRNA expression in blood vessels, liver, midgut, rectum and urethra was restricted to gestational days 16 and/or 20. The CRLR was thought to be a calcitonin gene-related peptide (CGRP) type 1 receptor (Aiyar et al., J. Biol. Chem., 271 (1996) 11325-11329). This contrasts with previously reported evidence that the CRLR is an orphan receptor with no identifiable interactions with CGRP and other related ligands (Flühmann et al., Biochem. Biophys. Res. Commun., 206 (1995) 341-347). In situ hybridization signals have not been detected in the cerebellum and the spleen known to present a high density of CGRP binding sites. The different regional distribution of CGRP receptor binding sites and CRLR mRNA implies the latter encoding a different CGRP receptor subtype. |
9452208 | Neuronal DNA damage precedes tangle formation and is associated with up-regulation of nitrotyrosine in Alzheimer's disease brain. | The relationship of neuronal DNA damage to tangle-bearing neurons and nitrotyrosine (NT) expression, a neurochemical marker of oxidative damage mediated by peroxynitrite, was examined in visual cortex of AD patients. Many terminal deoxynucleotidyl transferase (TdT)-positive neurons were detected and the majority (93%) of these TdT-labeled neurons lacked evidence of tangle formation. NT expression was elevated in AD cases and most TdT-labeled nuclei also showed strong NT immunoreactivity. These data suggest the hypothesis that the neurons with DNA damage in the absence of tangle formation may degenerate by tangle-independent mechanisms and that oxidative damage may contribute to such mechanisms in AD. |
9452209 | Direct projections from nucleus X to the external cortex of the inferior colliculus in the rat. | Direct projections from nucleus X to the external cortex of the inferior colliculus (ICe) were found in the rat by the retrograde single- and double-labeling methods. The projections are bilateral with a clear contralateral dominance. Some of these projections are made by axon collaterals of projection fibers from nucleus X to the ventrobasal thalamus. On the other hand, projection fibers from nucleus X to the cerebellum send no axon collaterals to ICe. |
9452210 | Voluntary alcohol drinking selectively accelerates dopamine release in the ventral striatum as reflected by 3-methoxytyramine levels. | Alcohol-preferring Alko, Alcohol (AA) rats with free access to food and water were taught to voluntarily consume 10% alcohol solution during 20-min sessions. After the drinking session, rats had elevated dopamine release (as reflected by 3-methoxytyramine concentrations) in the nucleus accumbens, olfactory tubercle, and caudate-putamen. When alcohol solution was replaced by plain water, dopamine release was increased only in the caudate-putamen, indicating selective activation of the mesolimbic dopaminergic pathway by alcohol. |
9452211 | Rapid changes in brainstem maps of adult primates after peripheral injury. | Cerebral cortical maps in adult primates reorganize within minutes-hours after peripheral injuries, but subcortical versus intracortical contributions to this rapid reorganization remain controversial. The present results show that injury of nerves to the hands of adult monkeys triggers rapid (minutes-hours) changes in maps of the hand in the brainstem main cuneate nucleus. These findings suggest that peripheral injury causes an initial concurrent reorganization of brainstem and cortical substrates and that early sensory changes emerge from reorganization involving multiple central levels. |
9452212 | PTH-related peptide-like immunoreactivity in the median emminence, paraventricular and supraoptic nuclei in colchicine-treated rats. | The existence of PTH-related peptide (PTHrP) in the hypothalamus was examined by immunohistochemistry in colchicine-treated rats. Two days after intracerebroventricular administration of colchicine dense PTHrP-like immunoreactivity (LI) was observed in the external zone of the median emminence (ME). PTHrP-LI cells were found in the paraventricular nucleus, the supraoptic nucleus and the periventricular region of the third ventricule. The effects of PTHrP on intracellular Ca2+ concentrations ([Ca2+]i) were examined by a Ca2+ imaging method using fura-2 in perifused preparations of isolated rat anterior pituitary cells. The rise in [Ca2+]i induced by PTHrP was found in approximately 17% of the cells examined. These results suggest that PTHrP-LI cells in the hypothalamus may project to the ME and contribute to the anterior pituitary function. |
9452213 | Glia are the main source of lactate utilized by neurons for recovery of function posthypoxia. | Experiments are described in which a rat hippocampal slice preparation was used along with the metabolic glial inhibitor, fluorocitrate (FC), to investigate the role of glial-made lactate and its shuttling to neurons in posthypoxia recovery of synaptic function. After testing two less effective concentrations of FC, only 10.1 +/- 6.5% of slices treated with 100 microM of the metabolic toxin recovered synaptic function at the end of 10-min hypoxia and 30-min reoxygenation. In contrast, 79.6 +/- 7.4% of control, untreated slices recovered synaptic function after 10-min hypoxia and 30-min reoxygenation. The low rate of recovery of synaptic function posthypoxia in FC-treated slices occurred despite the abundance of glucose present in the medium before, during, and after hypoxia. The amount of lactate produced by FC-treated slices during the hypoxic period was only 62% of that produced by control, untreated slices. Supplementing FC-treated slices with exogenous lactate significantly increased the posthypoxia recovery rate of synaptic function. These results strongly support our previous findings concerning the mandatory role of lactate as an aerobic energy substrate for the recovery of synaptic function posthypoxia and clearly show that the bulk of the lactate needed for this recovery originates in glial cells. |
9452214 | Mature sensory neuron-derived hybrid cell line expressing NGF-dependent neurite extension. | We established a hybrid cell line which extended neurites in the presence of nerve growth factor by fusion between adult mouse sensory neurons and neuroblastoma C1300 cells using emetine and actinomycin D. The serine-phosphorylated 200 and 160 kDa neurofilament proteins were detected in the hybrid cells. parison, C1300 cells expressed both subunit of non-phosphorylated neurofilaments at serine residues. |
9452215 | Protective effect of a low dose of colchicine on the delayed cell death of hippocampal CA1 neurons following transient forebrain ischemia. | Transient forebrain ischemia in rats preferentially causes neuron death in the striatum and hippocampal CA1 area. Prior injection of a low dose (1 microl) of colchicine (1 microM) into the unilateral hippocampus prevented ischemic damage of CA1 neurons in both hippocampal hemispheres, whereas no protection against ischemic damage was seen in the striatum. These results suggest that disconnection of hippocampal neurons by blockade of axoplasmic transport with colchicine specifically protects ischemic damage of CA1 neurons. |
9452216 | Changes in visceral pain reactivity as a function of estrous cycle in female rats with artificial ureteral calculosis. | This study examined estrous differences in the characteristics of behavioral crises of visceral pain in female rats video-taped throughout a 4-day period after implantation of an artificial stone in one ureter. All animals continued to have a regular cycle after ureteral surgery. In the recording period, the percentage of time spent in crises was significantly higher during metestrus/diestrus (M/D) than during proestrus/estrus (P/E) (P < 0.001, chi2-test). Mean duration plexity of crises were slightly higher in M/D than in P/E, but the difference was not significant. The results in this animal model show an enhancement of ureteral pain sensitivity in M/D, a finding in line with the clinical observation, in fertile women with urinary calculosis, of a greater incidence of colics in the perimenstrual period (equivalent to M/D in rats). |
9452217 | Dopamine release in striatal slices of rats previously submitted to electroconvulsive shock. | The effects of single and repeated electroconvulsive shock (ECS) on the release of dopamine from rat striatal slices were investigated using the fractional release technique. Experiments were performed 24 h after the single or the last of seven ECS sessions. Repeated, but not single, ECS was associated with reduced dopamine release in response to chemical stimulation. These results suggest that repeated ECS affects the regulation of striatal dopamine presynaptic receptors. |
9452218 | Individual pineal cells in chick possess photoreceptive, circadian clock and melatonin-synthesizing capacities in vitro. | Chick pineal cells express a circadian rhythm of melatonin release under light-dark (LD) cycles, with an increase during the dark period and a decrease during the light period, and this rhythm persists under constant darkness (DD). We cultured individual single pineal cells with 15 microl of medium per well in a Terasaki plate and measured melatonin secretion every 12 h under LD, DL and DD. Individual cells secreted more melatonin during the dark period than during the light period under both LD and DL conditions, and those rhythmic secretions persisted under DD. These results suggest that individual pineal cells in chick have photoreceptive, circadian clock and melatonin-synthesizing capacities. |
9452219 | Hypoxic ventilatory roll-off is associated with decreases in protein kinase C activation within the nucleus tractus solitarius of the rat. | Protein kinase C (PKC) inhibition attenuates ventilatory responses to acute hypoxia. Hypoxic ventilatory roll-off (VRO) could reflect underlying changes in PKC activity. Immunoblots of NTS lysates harvested at peak ventilation revealed subcellular translocations of particular PKC isoforms which coincided with PKC activity elevations. In contrast, reductions in PKC activity occurred during VRO, itant with selective decreases in PKCbeta and -delta translocation. Thus, alterations in PKC activity within the NTS which occur over time during hypoxia are isoform-selective and coincide with changes in ventilation. |
9452220 | Differential co-localization of nicotinic acetylcholine receptor subunits with calcium-binding proteins in retinal ganglion cells. | Immunohistochemistry was used to examine the co-occurrence of nicotinic acetylcholine receptor subunits with calcium-binding proteins in ganglion cells of the chick retina. The alpha3 subunit was rarely observed in ganglion cells containing calbindin, calretinin, or parvalbumin. On the other hand, the alpha8 subunit was more often co-localized with all calcium-binding proteins studied. These results may be related to the high calcium permeability of nicotinic receptors that contain the alpha8 subunit. |
9452221 | Increased astrocytic expression of metallothioneins I + II in brainstem of adult rats treated with 6-aminonicotinamide. | The cerebral distribution of metallothioneins I and II (MT-I + II) was studied in adult rats subjected to i.p. injection with the gliotoxin 6-aminonicotinamide (6-AN). Grey matter regions of the brainstem heralded numerous OX-42-positive macrophages and microglia, indicating that 6-AN primarily caused damage to this part of the brain. In the grey matter regions infiltrated with OX-42-positive cells, astrocytes identified by anti-GFAP and MT-I + II antibodies were almost absent. By contrast, in the peripheral zone of the lesioned regions numerous reactive GFAP- and MT-I + II-positive astrocytes were observed. The blood-brain barrier (BBB) to serum albumin promised in the entire brainstem. The astrocytic expression of MT-I + II could reflect the brains needs to scavenge metal ions released from either damaged cells or plasma proteins entering the brain due to the injured BBB, as well as it could reflect the potential antioxidant function of MT-I + II. |
9452222 | Selective dopamine neurotoxicity by an industrial chemical: an environmental cause of Parkinson's disease? | While unproved, environmental toxins of industrial and or agricultural origin represent an attractive theory to explain the increasing incidence of degenerative diseases of the nervous system such as Parkinson's disease (PD). We have examined several chemicals utilized in an area of Israel previously demonstrated to contain a statistically greater than average number of people with Parkinson's disease. One of these agents, a light stabilizer employed universally in the production of polyolifins used in plastics, depleted primary mesencephalic cultures of dopamine neurons, and produced a dopamine-specific lesion of the substantia nigra pacta when injected stereotactically into the ventral midbrain of adult rats. The observed effects were dose-dependent. These findings represent a potentially significant development in the search for industrial/environmental causes of neurodegenerative disease. |
9452223 | Tryptophan ingestion by gestant mothers alters prolactin and luteinizing hormone release in the adult male offspring. | The effect of tryptophan administration to pregnant rats on the development of serotonergic systems and serotonin-related hormones in the offspring was studied. The male offspring of rats treated with tryptophan (200 mg/kg/day) during the second half of gestation showed a 4- to 7-fold increase in serum prolactin 40 and 70 days after birth and a 2-fold increase in serum luteinizing hormone 70 days after birth. The forebrain of adult offspring of tryptophan-treated rats showed an increase in serotonin and 5-hydroxyindoleacetic acid levels. Present data suggest that tryptophan regulates serotonergic differentiation during early development. |
9452224 | Central application of a nitric oxide donor activates heat defense in the rabbit. | In chronically instrumented, conscious rabbits at moderately warm ambient thermal conditions, infusion of the NO-donor SIN-1 into the anterio-ventral 3rd cerebral ventricle (1-2 microg/min per kg BW, 2-4 microl/min, 30 min) initiated a co-ordinated activation of autonomic heat loss mechanisms, as indicated by the rise in ear skin temperature and by increases in panting frequency and respiratory evaporative water loss, while oxygen consumption decreased slightly. The heat loss responses were similar to those attributed to NO in studies employing systemic application of NO-donors. Different from NO acting peripherally, which causes arterial hypotension and tachycardia, centrally acting NO induced arterial hypertension and bradycardia. The observation of the same heat loss responses despite opposing circulatory actions suggests that NO is specifically involved in thermoregulation as a central activator of heat defense mechanisms. |
9452225 | Hydrocephalus and craniosynostosis. | A retrospective study of 1727 cases of craniosynostosis was undertaken to determine the interrelationship between abnormal cerebrospinal fluid (CSF) hydrodynamics and craniosynostosis. |
9452226 | Treatment of high-grade spinal cord astrocytoma of childhood with "8-in-1" chemotherapy and radiotherapy: a pilot study of CCG-945. Children's Cancer Group. | The purpose of this study was to devise an improved method of treating high-grade gliomas of the spinal cord in children who have a dismal prognosis following conventional treatment. |
9452227 | Follow-up results of using microvascular decompression for treatment of glossopharyngeal neuralgia. | Glossopharyngeal neuralgia (GPN) is an mon disorder that is characterized by a severe lancinating monly induced by swallowing. There has been some debate among various authors as to which surgical procedure should be adopted to treat cases of GPN: microvascular pression (MVD) or partial rhizotomy. The latter necessitates the partial destruction of normal neural structures. |
9452228 | Magnetic resonance evaluation of ventrolateral medullary compression in essential hypertension. | The authors designed a blinded prospective paring patients with essential hypertension to patients without hypertension in which magnetic resonance (MR) imaging was used to evaluate the role of lateral pression by adjacent vascular structures as a cause of neurogenic hypertension. |
9452229 | Neurovascular decompression of the eighth cranial nerve in patients with hemifacial spasm and incidental tinnitus: an alternative way to study tinnitus. | The authors sought to clarify the clinical characteristics of tinnitus resulting from pression (NVC) of the eighth cranial nerve. |
9452230 | Acquired Chiari I malformation secondary to spontaneous spinal cerebrospinal fluid leakage and chronic intracranial hypotension syndrome in seven cases. | Spontaneous spinal cerebrospinal fluid (CSF) leakage with development of the intracranial hypotension syndrome and acquired Chiari I malformation due to lumbar spinal CSF diversion procedures have both been well described. However, itant presentation of both syndromes has rarely been reported. The object of this paper is to present data in seven cases in which both syndromes were present. Three illustrative cases are reported in detail. |
9452231 | Surgical treatment of spontaneous spinal cerebrospinal fluid leaks. | Spontaneous spinal cerebrospinal fluid (CSF) leaks are an increasingly recognized cause of intracranial hypotension and may require neurosurgical intervention. In the present report the authors review their experience with the surgical management of spontaneous spinal CSF leaks. |
9452232 | Magnetic resonance imaging findings in ossification of the posterior longitudinal ligament of the cervical spine. | Because of the lack of magnetic resonance (MR) signal from cortical bones, MR imaging is inadequate for diagnosing ossified lesions in the spinal canal. However, MR imaging provides important information on spinal cord morphology and associated soft-tissue abnormality. The purpose of this study is to determine the role of MR imaging in the diagnosis and treatment of patients with ossification of the posterior longitudinal ligament (OPLL) of the cervical spine. |
9452233 | A comparative analysis of fusion rates and donor-site morbidity for autogeneic rib and iliac crest bone grafts in posterior cervical fusions. | Autogeneic bone graft is often incorporated into posterior cervical stabilization constructs as a fusion substrate. Iliac crest is used frequently, although donor-site morbidity can be substantial. Rib is used rarely, despite its accessibility, expandability, unique curvature, and high bone morphogenetic protein content. The authors present parative analysis of autogeneic rib and iliac crest bone grafts, with emphasis on fusion rate and donor-site morbidity. |
9452234 | Evaluation of intercostal to musculocutaneous nerve transfer in reconstructive brachial plexus surgery. | Direct coaptation of intercostal nerves (ICNs) to the musculocutaneous (MC) nerve was performed to restore elbow flexion in 25 patients with brachial plexus root avulsions. |
9452235 | Is routine transcranial Doppler ultrasound monitoring useful in the management of subarachnoid hemorrhage? | In this prospective observational study, the authors assess the impact of routine transcranial Doppler (TCD) ultrasound monitoring on the diagnosis, management, and e of delayed ischemic neurological plicating subarachnoid hemorrhage (SAH). |
9452236 | Comparison of balloon angioplasty and papaverine infusion for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage. | The purpose of this study was to test the hypothesis that balloon angioplasty is superior to papaverine infusion for the treatment of proximal anterior circulation arterial vasospasm following subarachnoid hemorrhage (SAH). Between 1989 and 1995, 125 vasospastic distal internal carotid artery or proximal middle cerebral artery vessel segments were treated in 52 patients. |
9452237 | Arteriovenous malformations in the basal ganglia and thalamus: management and results in 101 cases. | Because arteriovenous malformations (AVMs) in the basal ganglia and thalamus are difficult to treat, the authors conducted a retrospective study to determine the best management strategy for these lesions. |
9452238 | Radiosurgery for cavernous malformations. | The authors examined 22 patients with cavernous malformations (CMs) who had undergone gamma knife radiosurgery (GKRS) to assess the value of this procedure in treating these lesions. |
9452239 | Role of ferrous iron chelator 2,2'-dipyridyl in preventing delayed vasospasm in a primate model of subarachnoid hemorrhage. | Oxyhemoglobin (HbO2) causes vasospasm after subarachnoid hemorrhage (SAH). The most likely ponent of HbO2 is iron. Various iron chelators, such as deferoxamine, have prevented vasospasm in vivo with limited success. However, only chelators of iron in the ferric state have been studied in animal models of vasospasm after SAH. Because free radical formation requires the ferrous (Fe++) moiety and Fe++ is a potent binder of the vasodilator nitric oxide, the authors hypothesized that iron in the ferrous state causes vasospasm and that chelators of Fe++, such as 2,2'-dipyridyl, may prevent vasospasm. This study was undertaken to investigate the influence of 2,2'-dipyridyl on vasospasm after induction of SAH in a primate model. |
9452240 | Platelet-activating factor and edema surrounding meningiomas. | The purpose of this study was to evaluate the involvement of platelet-activating factor (PAF) in the formation of edema surrounding meningiomas. |
9452241 | Efficacy and biocompatibility of a photopolymerized, synthetic, absorbable hydrogel as a dural sealant in a canine craniotomy model. | A canine craniotomy model was used to evaluate the dural sealing efficacy and patibility of a novel, synthetic, bioresorbable hydrogel. |
9452242 | Adult neuronal ceroid lipofuscinosis with clinical findings consistent with a butterfly glioma. Case report. | The authors report a case of neuronal ceroid lipofuscinosis (Kufs' disease) confirmed by stereotactically obtained brain biopsy findings and initially diagnosed as a butterfly glioma. The presenting symptoms in the 64-year-old patient were mental alterations with progressive dementia, followed by muscular atrophy and myoclonia with distal preponderance. The mild initial disturbances of coordination increased, and the patient developed a markedly ataxic gait. Computerized tomography (CT) scanning and magnetic resonance imaging revealed generalized cerebral atrophy and a bifrontal space-occupying lesion involving the callosum. The original "clearcut" diagnosis of glioblastoma multiforme, based on CT scans, was unexpectedly disproved by examination of stereotactically obtained brain biopsy specimens, which revealed a neuronal ceroid lipofuscinosis (Kufs' disease). To the authors' knowledge, this is the first report of a case presenting with both diffuse brain atrophy and localized accumulation of neuronal lipofuscin, mimicking a mass lesion on radiological studies. |
9452244 | Malignant transformation of ganglioneuroma into spinal neuroblastoma in an adult. Case report. | Ganglioneuroma is generally considered to be a benign tumor and potentially surgically curable. The authors present a case of a 21-year-old woman who underwent resection of a retroperitoneal ganglioneuroma and developed spinal neuroblastoma 11 years later. She has survived 10 more years with only recent development of metastases. To the authors' knowledge, this is the first report of malignant transformation of a ganglioneuroma into a neuroblastoma. Also, such long-term survival in an adult with spinal neuroblastoma has not been reported previously. This case raises the possibility of a dedifferentiating potential for ganglion cells in a ganglioneuroma or the presence of a long-term, quiescent form of neuroblastoma. |
9452243 | Chordoid meningioma in a child. Case report. | A case of chordoid meningioma occurring in a 15-year-old girl is presented. The patient manifested seizures as the initial symptom and subsequently exhibited subclinical microcytic hypochromic anemia. The tumor, located in the falcotentorial region and associated with diffuse edema, was totally resected. On histological examination of the surgical specimen, the clustering pattern of partly vacuolated cells in the mucoid stroma mimicked chordoma; however, positive staining of individual cells for vimentin and epithelial membrane antigen led to a diagnosis of meningioma. Interestingly, the tumor cells were surrounded by a periodic acid-Schiff- and type IV collagen-positive substance. Electron microscopy demonstrated a strikingly dense and thick basal lamina. The patient's microcytic hypochromic anemia disappeared after the tumor was removed. Both the clinical and pathological features of this case resemble those of chordoid meningioma, a rare meningioma variant. |
9452245 | Preoperative treatment with botulinum toxin to facilitate cervical fusion in dystonic cerebral palsy. Report of two cases. | The authors report the use of high-dose botulinum toxin A for muscle relaxation prior to surgery for cervical spine fixation in two patients with dystonic cerebral palsy that included severe cervical dystonia. Both patients had recently developed progressive cervical myelopathy and surgery was planned to halt the insidious progressive weakness. However, marked dystonic posturing of the neck would promised their tolerance of halo fixation and subsequently impeded postoperative fusion. Preoperative chemodenervation of selected cervical muscles with injections of high-dose botulinum toxin A eliminated all involuntary neck movements, permitting the patients to tolerate halo fixation and facilitating postoperative spinal fusion. It is concluded that botulinum toxin A can be used safely and effectively in the preoperative management of patients with cervical dystonia and cervical spondylitic myelopathy. |
9452246 | Idiopathic spinal cord herniation. Report of two cases and review of the literature. | The authors describe two occurrences of idiopathic spinal cord herniation, an entity that has been reported previously in only 11 cases. The patients described in this report presented in midlife with Brown-Séquard syndrome. Computerized tomography myelography and magnetic resonance (MR) imaging showed ventral displacement of the spinal cord with no apparent dorsal mass. Intraspinal cerebrospinal fluid (CSF) flow studies in which phase-contrast pulse sequence cine MR imaging was used displayed a normal pattern dorsal to the spinal cord. Percutaneous intrathecal endoscopic observation did not disclose dorsal intradural cysts, but ventral adhesions were seen between the spinal cord and the dura. Microsurgical intradural exploration revealed ventrolateral herniation of the cord and a ventral root through a dural defect into an epidural arachnoid cyst. The adhesions were released, the cord was repositioned intradurally, and the dural defect was patched. The patients showed gradual improvement postsurgery, as did most of the patients in the previously reported cases. The CSF flow and endoscopic studies were found to be particularly informative, and dural patching with surgical membrane is mended. |
9452247 | Intracranial repair of a divided trochlear nerve. Case report. | The authors report the case of a 37-year-old woman in whom the trochlear nerve was transected during removal of a meningioma in the cavernous sinus and subsequently repaired by using microsurgical techniques. This patient presented with a tumor in the posterior part of the right cavernous sinus with expansion over the tentorium. Preoperatively, she suffered from partial deficit of the right trochlear nerve. Intraoperatively, the trochlear nerve was noted to pletely encased by the tumor and was totally divided during removal of the lesion. After tumor resection, the trochlear nerve was repaired by using a sural nerve fascicle secured with sutures and fibrin glue. Six months after the operation, trochlear nerve regeneration became evident as the patient's binocular vision gradually improved. The patient regained normal functioning of the superior oblique muscle 3.5 years after surgery. It is concluded that repair of a divided trochlear nerve is worthwhile and can be followed by successful regeneration and an excellent functional recovery of the superior oblique muscle. |
9452248 | Role of surgical resection in the treatment of hypothalamic hamartomas causing precocious puberty. Report of six cases. | Hypothalamic hamartomas (HHs) are benign tumors that are often associated with central precocious puberty. Resection of HHs has been mended as a treatment option for selected cases of pedunculated lesions, especially in young children. The role of surgery has to be evaluated in the light of the availability of effective medical treatment with gonadotropin-releasing hormone analogs (GnRHas). The authors report the long-term results of total resection of HHs in two children with central precocious puberty pare it with medical management in four children. The two surgically treated patients underwent total resection of pedunculated HHs at 1.75 (Case 1) and 3.25 years (Case 2) and have received follow-up care for 9 and 8 years, respectively. There were no plications puterized tomography scanning plete tumor removal in both patients. Both patients subsequently experienced some regression of secondary sexual characteristics. The response of luteinizing hormone to GnRH became prepubertal in one patient and was diminished in the other. However, the growth velocity remained elevated (> 7 cm/year), bone age remained advanced (> +2 standard deviations) 5 years after surgery, decreasing adult height prediction. In one child, GnRHa therapy was initiated 7 years postsurgery. Four children were treated solely with GnRH agonists and have received follow-up care for 2.3, 6, 9, and 9 years, respectively. These patients have had plete regression of endocrinological abnormalities, including a normalization of growth velocity and reduction in the rate of skeletal maturation. No side effects were noted with decapeptyl treatment, and one child developed sterile abscesses while receiving Lupron-Depot. The proven efficacy of GnRHa in suppressing puberty and reducing bone age advancement leads the authors to advise against surgery as the initial management of central precocious puberty caused by HHs. |
9452249 | Sequential outer table craniotomy a in hyperossified meningioma. Technical note. | A hyperossified meningioma with significant calvarial thickening is mon. Craniectomy of the involved region followed by cranioplasty is usually required to resect the bone overgrowth. However, in some cases, the hyperossified calvaria is too thick to allow safe penetration with a craniotome or trephine. In this report, the authors present a technique for preserving the outer calvaria while still resecting the majority of the underlying tumor mass. The key is to perform a craniotomy in a region adjacent to the hyperossified bone and to remove the tumorous, ossified inner table through this "window" by means of a high-speed drill. A second craniotomy can then be performed over the undermined area; this maneuver can be advanced and repeated until the tumor is resected. Frameless stereotactic guidance and microplates are useful in performing this procedure. |
9452250 | Rapid termination of intraoperative stimulation-evoked seizures with application of cold Ringer's lactate to the cortex. Technical note. | One major risk of intraoperative stimulation mapping is the production of stimulation-evoked seizures. Cold Ringer's lactate solution was applied directly to the irritated cortex in 22 patients with stimulation-induced seizures that occurred during intraoperative brain mapping procedures. The irrigation rapidly and reliably terminated these simple partial seizures and eliminated the need for intravenously administered short-acting barbiturates with antiepileptic properties. The authors describe a practical and simple method for controlling stimulation-induced seizure activity during brain mapping procedures. |
9452258 | Radiotherapy for patients with medically inoperable Stage I nonsmall cell lung carcinoma: smaller volumes and higher doses--a review. | Surgical resection remains the treatment of choice for patients with stage I nonsmall cell lung carcinoma. However, there is a group of patients who are medically inoperable and are treated with radiotherapy alone. This review summarizes findings from published series of radiotherapy for patients with medically inoperable Stage I lung carcinoma. |
9452259 | Basal cell adenocarcinoma of the salivary glands: comparison with basal cell adenoma through assessment of cell proliferation, apoptosis, and expression of p53 and bcl-2. | Basal cell adenocarcinoma (BCAC) of the salivary gland is a rare tumor and recently described entity. Eleven cases of BCAC are presented here pared with basal cell adenoma (BCA) through assessment of cell proliferative activity, apoptosis, and expression of p53, bcl-2, and epidermal growth factor receptor (EGFR) because these two tumors show close similarity in some cytologic and architectural characteristics. |
9452260 | Olive oil, other seasoning fats, and the risk of colorectal carcinoma. | An association between fats and colorectal carcinoma has been suggested, but the epidemiologic evidence by type of dietary fat is far less clear. Colorectal carcinoma rates have been relatively low in Mediterranean pared with most other Western countries, but ponents of the Mediterranean diet responsible for this favorable pattern are unclear. |
9452261 | Genomic aberrations in early stage human hepatocellular carcinomas. | Primary liver cancer, which most often takes the form of hepatocellular carcinoma (HCC), is among the 10 mon cancers in humans worldwide. In hepatocarcinogenesis, evidence of a multistep process is supported by the marked increase of HCC incidence with age; most HCCs are diagnosed in the second half of life, generally after a long period of chronic liver disease and in frequent association with cirrhosis. This long process may be correlated with the development of multiple genetic lesions, the origin of which currently remain largely unknown. In a previous study, the authors collected data on genomic DNA aberrations in primary HCC by restriction landmark genomic scanning (RLGS), a powerful screening method for the human genome. |
9452262 | Pulmonary blastoma: case report of a patient with a 7-year remission and review of chemotherapy experience in the world literature. | Pulmonary blastoma is a rare malignant neoplasm for which there currently are no treatment guidelines. |
9452263 | Detection of chromogranin A mRNA in small cell lung carcinoma using a new, highly sensitive in situ hybridization method with a non-radioisotope oligonucleotide probe. | Immunoreactivity for chromogranin A (Cg A) is associated with the presence of neurosecretory granules in tumor cells, but immunohistochemical staining for Cg A may be absent in small cell lung carcinoma (SCLC), which has only a few secretory granules. Localization of Cg A mRNA is a useful indicator of the site of synthesis of a particular protein and possibly the rate of synthesis, and it is not dependent on posttranslation events within the cells. However, it is difficult to detect the low levels of mRNA copies using the standard non-radioisotope (RI) oligonucleotide probe. |
9452264 | Evidence of an association between 6q13-21 chromosome aberrations and locally aggressive behavior in patients with cartilage tumors. | The finding of a cytogenetic-pathologic correlation plex karyotypes and high grade cartilaginous tumors has been reported. However, few cytogenetic reports exist regarding benign or low grade lesions. A subset of low grade malignant cartilaginous tumors is characterized by locally aggressive behavior but no metastatic potential. Because the histopathologic distinction between benign, borderline, or low grade malignant cartilaginous lesions can be difficult, the finding of additional tumor markers associated with the clinical behavior of borderline cartilaginous lesions could be clinically significant. |
9452265 | Invasive infection due to Trichosporon cutaneum in patients with hematologic malignancies. | Invasive infection due to Trichosporon is a rare but often fatal disease in promised patients. In this study, data on patients with hematologic malignancies who had an invasive infection due to Trichosporon diagnosed at the Tokyo Metropolitan Komagome Hospital in Tokyo, Japan, were analyzed. |
9452266 | Possible association between adult T-cell leukemia/lymphoma and acute myeloid leukemia. | To the authors' knowledge, an association between adult T-cell leukemia/lymphoma (ATL) and acute myeloid leukemia (AML) has been reported only in four patients. The authors identified five additional patients with both neoplasms. |
9452267 | The effects of different antineoplastic agents and of pretreatment by modulators on three melanoma lines. | The chemotherapy of melanoma patients must be improved because of the naturally poor response and acquired resistance of this disease. |
9452268 | A Phase II trial of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin in the treatment of patients with locally advanced breast carcinoma. | Traditionally, primary surgical therapy is considered unsuitable for the treatment of patients with locally advanced breast carcinoma (LABC). Multiple reports have documented the efficacy of primary chemotherapy in this group of patients. The purpose of this study was to investigate the efficacy of a multimodality treatment program in reducing distant and local disease relapses in patients with LABC. |
9452269 | Prognostic factors in uterine carcinosarcoma: a clinicopathologic study of 25 patients. | a (malignant mixed mullerian tumor) of the female genital tract is a highly malignant neoplasm. The tumor stage and histologic grade of the ponent are among the important prognostic indicators cited in the literature for this tumor. |
9452270 | Tumor angiogenesis, hepatocyte growth factor, and c-Met expression in endometrial carcinoma. | This study was designed to evaluate the significance of tumor angiogenesis and angiogenic factors such as hepatocyte growth factor (HGF) and c-Met in determining the prognoses of 93 patients with endometrial carcinoma. |
9452271 | A five-alpha reductase inhibitor or an antiandrogen prevents the progression of microscopic prostate carcinoma to macroscopic carcinoma in rats. | The objective of this study was to elucidate the prophylactic effects of 5-alpha reductase inhibitor (e.g., finasteride) and a pure antiandrogen (e.g., casodex) on rat prostate carcinogenesis and to determine whether latent prostate carcinoma can be prevented to develop to clinically significant cancer by use of these drugs. |
9452272 | A French national epidemiologic survey on renal cell carcinoma. Oncology Committee of the Association Française d'Urologie. | In this multicenter study, the yearly national evaluation of tumors of the kidney was out by the Oncology Committee of the French Association of Urology. |
9452273 | Malignant intracerebral nerve sheath tumor: a case report and review of the literature. | Intraparenchymal nerve sheath tumors of the central nervous system are rare, usually benign tumors. Three cases with tumor recurrences have previously been reported in the literature. The authors report a case of a malignant intracerebral nerve sheath tumor in a girl age 8 years and analyze the biologic characteristics of this tumor. |
9452274 | Effects of medroxyprogesterone acetate on food intake, body composition, and resting energy expenditure in patients with advanced, nonhormone-sensitive cancer: a randomized, placebo-controlled trial. | Anorexia and cachexia are well-known sequelae of cancer that contribute to morbidity and mortality. In several studies in patients with non-hormone-sensitive tumors, synthetic progestogens were shown to exert beneficial effects on appetite and weight loss. The current study was undertaken to investigate the effects of medroxyprogesterone acetate (MPA) on food intake, position, and resting energy expenditure (REE). |
9452275 | A Phase I trial of ifosfamide and paclitaxel with granulocyte-colony stimulating factor in the treatment of patients with refractory solid tumors. | Ifosfamide and paclitaxel are antineoplastic agents with broad activity and with different mechanisms of action. A Phase I trial was conducted to determine the maximum tolerated dose and associated toxicities of these agents when used bination. |
9452276 | Mantle cell lymphoma: presenting features, response to therapy, and prognostic factors. | The goal of this study was to analyze the presenting features, natural history, and prognostic factors in 59 patients with well characterized mantle cell lymphoma (MCL). |
9452277 | Serum CA 125 is of clinical value in the staging and follow-up of patients with non-Hodgkin's lymphoma: correlation with tumor parameters and disease activity. | CA 125 is a glycoprotein produced by epithelial ovarian tumors and by mesothelial cells; its levels also have been shown to be elevated in patients with non-Hodgkin's lymphoma (NHL). |
9452278 | The use of epithelial membrane antigen and silver-stained nucleolar organizer regions testing in the differential diagnosis of mesothelioma from benign reactive mesothelioses. | The accurate diagnosis of pleural lesions obtained from small closed biopsy is difficult. As yet there is no single reliable test to distinguish between malignant and benign mesothelial tissue. |
9452279 | Flow cytometric analysis of peripheral blood and bone marrow for tumor cells in patients with neuroblastoma. | Several sensitive surveillance tests reportedly have been used to detect occult neuroblastoma (NB) cells in peripheral blood (PB) and bone marrow (BM). They may be useful in monitoring minimal residual tumor cells. The authors report the feasibility and clinical usefulness of a sensitive flow cytometric assay that has been newly developed and evaluated to detect NB cells. |
9452280 | Treatment of patients with acute lymphoblastic leukemia with bulky extramedullary disease and T-cell phenotype or other poor prognostic features: randomized controlled trial from the Children's Cancer Group. | Children with acute lymphoblastic leukemia with multiple poor prognostic factors and who have a lymphomatous mass at diagnosis, whether of T- or non-T-immunophenotype, are at increased risk of short term remission and extramedullary recurrence, and are in need of better therapies. |
9452282 | A controlled trial of lambda-cyhalothrin-impregnated bed nets and/or dapsone/pyrimethamine for malaria control in Sierra Leone. | A randomized controlled trial investigated the impact munity-wide use of mosquito nets impregnated with lambda-cyhalothrin alone or with dapsone/pyrimethamine (d/p) prophylaxis on clinical malaria due to perennially transmitted Plasmodium falciparum in children in the Bo district of Sierra Leone. The 17 munities were pair-matched and randomly allocated to receive treated mosquito nets or no nets and the children (age range = 3 months-6 years) in munity were randomly allocated to receive d/p or placebo individually every two weeks. This resulted in each of the approximately 2,000 children recruited being in one of four study groups (impregnated mosquito nets and d/p prophylaxis, impregnated mosquito nets, d/p prophylaxis, and controls). The intervention phase of the study lasted 12 months. A total of 1,800 children attended more than 25% of the 48 total weekly morbidity surveillance surveys and were included in the analysis. The effects of the exclusive use of either treated mosquito nets or d/p prophylaxis on protection against clinical malaria due to P. falciparum was significantly similar (49% and 42%, respectively), while bination this protective efficacy was significantly increased to 72% (95% confidence interval = 67-76%). Children in the control group had an average of 1.3 clinical malaria episodes per child pared with 0.65 episodes or 0.78 episodes for those using treated mosquito nets and d/p, respectively. Children using both treated mosquito nets and d/p prophylaxis had an average of 0.37 episodes per child. The interventions significantly reduced spleen rates and increased hematocrit values, and reduced the duration of episodes of clinical malaria. |
9452283 | The molluscicidal activity of Crown of Christ (Euphorbia splendens var. hislopii) latex on snails acting as intermediate hosts of Schistosoma mansoni and Schistosoma haematobium. | The present study describes the action of the latex of Euphorbia splendens var. hislopii (E. milli) on species of the genus Bulinus and on Biomphalaria pfeifferi, intermediate hosts of schistosomiasis in Africa, and the Brazilian snails B. glabrata, B. tenagophila, and B. straminea, intermediate hosts of schistosomiasis in Brazil. The impact of the latex on the egg masses and embryos of B. glabrata was also evaluated. Using the standardized methodology of the World Health Organization for testing plant-derived molluscicides, we obtained a 90% lethal dose (LD90) ranging from 0.13 ppm for B. glabrata subjected to lyophilized latex to 4.0 ppm for B. pfeifferi tested with the natural latex. This material has proved to be one of the most potent and specific plant molluscicides discovered thus far, presenting advantages in terms of application so that it could be used in programs munity participation in endemic areas in both Brazil and Africa. |
9452284 | Comparative clinical trial of artesunate suppositories and oral artesunate in combination with mefloquine in the treatment of children with acute falciparum malaria. | A randomized pilot study pare the safety and efficacy of artesunate suppositories (15 mg/kg/day for three days) versus oral artesunate (6 mg/kg/day for three days), both bination with mefloquine (25 mg/kg), was conducted in 52 Thai children with plicated multidrug-resistant falciparum malaria. Forty-five patients (87%) had a full 28-day follow-up in the hospital to assess efficacy and exclude reinfection. Mean [range] times to fever clearance of the two groups were similar (42 hr [15-104] versus 42 hr [6-119]). Artesunate suppositories resulted in significantly longer times to achieve 50% and 90% reductions of the initial parasite counts (17 and 26 hr versus 9 and 15 hr; P < 0.05 and P < 0.001). Time [range] to parasite clearance was longer in the artesunate suppositories group (42 hr [14-93] versus 35 hr [16-69]), but the difference was not significant. The cure rates by days 28 were not significantly different, 92% for artesunate suppository-treated patients and 100% for oral artesunate-treated patients. Both drug regimens are safe and effective. Further studies are needed to characterize the pharmacokinetic properties and the optimum regimen of artesunate suppositories for the treatment of severe malaria. |
9452285 | Post-marketing surveillance of prophylactic mefloquine (Lariam) use in pregnancy. | The purpose of this study was to evaluate the teratogenic potential of mefloquine (Lariam) in pregnancy, based on the Roche International Spontaneous Reporting System. Lariam is an anti-malarial drug used both in prophylaxis and treatment of malaria. Teratogenic effects were observed in animals but data from humans are lacking. Women of childbearing potential are currently advised to take contraceptive precautions up to three months after the last dose. The study included 1,627 spontaneous reports of women exposed to Lariam before or during pregnancy, which were received by Roche worldwide since introduction on the market. The data were analyzed considering pregnancy and fetal e and type of congenital malformations. The birth prevalence of congenital malformations in women exposed to Lariam is estimated to be 4% and is not different from the prevalence observed in the general population. In addition, the congenital malformations observed with Lariam exposure do not show any specific pattern. The data from our study suggest that the teratogenicity, which was observed in animals at high doses, cannot be applied to humans. |
9452286 | Prognostic factors of green pit viper bites. | Clinical features of green pit viper bites vary from asymptomatic to fatal bleeding. Antivenin promptly reverses the coagulopathy but has considerable adverse side effects. In this study, potential clinical predictors of severe es (wound necrosis, wound infection, and systemic bleeding) and antivenin allergy were determined in 271 moderate to severe cases of green pit viper bites by multivariate analysis. The incidences of systemic bleeding, wound necrosis, secondary infection, and antivenin allergy were 17.3%, 6.6%, 5.5%, and 20.8% respectively. The predictors of systemic bleeding were bination of thrombocytopenia and prolonged venous clotting time and bite sites away from digits. A bite on the fingers or toes was a risk factor for skin necrosis (P = 0.03). Systemic absorption of the venom from digits may be poor, resulting in severe local but mild systemic effects. The presence of blisters often led to necrosis and secondary infections (P = 0.0037 and P = 0.0006, respectively). Although negative skin test results do not exclude the possibility of antivenin allergy, positive results indicate a high risk (P = 0.016) requiring special precautions. |
9452287 | Short report: endomyocardial fibrosis and cardiomyopathy in an area endemic for schistosomiasis. | An association of schistosomiasis and endomyocardial fibrosis or cardiomyopathy has been suggested. Clinical, stool, abdominal ultrasound, electrocardiogram, and Doppler echocardiogram examinations were performed on 226 patients from an area endemic for schistosomiasis. The diagnosis of schistosomiasis was made in 152 patients (69%) but clinical, electrocardiographic, or Doppler echocardiographic evidence of a schistosome cardiomyopathy or endomyocardial fibrosis could not be detected in any patient. |
9452288 | Tuberculosis meningitis, Abbassia Fever Hospital-Naval Medical Research Unit No. 3-Cairo, Egypt, from 1976 to 1996. | A total of 1,430 patients with the presumptive diagnosis of tuberculous meningitis were admitted to the U.S. Naval Medical Research Unit No. 3/Abbassia Fever Hospital in Cairo, Egypt from January 1976 to January 1996. Diagnosis was confirmed by culture of the mycobacteria from the cerebrospinal fluid CSF of 857 patients and these patients are included in the final analysis. There were 497 males and 360 females. The patients ranged in age from five months to 55 years. The number of patients admitted during the months of March, April, and May were more than double those admitted during October, November, and December. The duration of symptoms prior to admission ranged from seven to 90 days (mean = 29.5 days). Upon admission, 4% of the patients were alert, 34% were drowsy, and 62% were in a. Of the 857 patients studied, 490 (57%) died, 256 (30%) pletely, and 11 (13%) recovered with sequelae. The mortality and neurologic sequelae were directly related to the stage of disease and duration of symptoms prior to admission. Mortality was significantly lower in patients admitted in stage II and or with short duration of pared with those in stage III and or with prolonged duration of symptoms prior to admission. The use of dexamethasone in patients with tuberculous meningitis significantly reduced the plications that occur in these patients and also significantly reduced the fatality rate. |
9452289 | Venezuelan equine encephalitis febrile cases among humans in the Peruvian Amazon River region. | A survey was conducted from October 1, 1993 to June 30, 1995 to determine the arboviral etiologies of febrile illnesses in the city of Iquitos in the Amazon River Basin of Peru. The study subjects were patients who were enrolled at medical care clinics or in their homes by Peruvian Ministry of Health (MOH) workers as part of the passive and active disease surveillance program of the MOH. The clinical criterion for enrollment was the diagnosis of a suspected viral-associated, acute, undifferentiated febrile illness of < or = 5 days duration. A total of 598 patients were enrolled in the study. Demographic information, medical history, clinical data, and blood samples were obtained from each patient. The mon clinical features were fever, headache, myalgia, arthralgia, retro-ocular pain, and chills. Sera were tested for virus by the newborn mouse and cell culture assays. Viral isolates were identified initially by immunofluorescence using polyclonal antibody. An ELISA using viral-specific monoclonal antibodies and nucleotide sequence analysis were used to determine the specific variety of the viruses. In addition, thin and thick blood smears were observed for malaria parasites. Venezuelan equine encephalitis (VEE) virus subtype I, variety ID virus was isolated from 10 cases, including three cases in October, November, and December 1993, five cases in January and February 1994, and two cases in June 1995. The ELISA for IgM and IgG antibody indicated that VEE virus was the cause of an additional four confirmed and four presumptive cases, including five from January through March 1994 and three in August 1994. Sixteen cases were positive for malaria. The 18 cases of VEE occurred among military recruits (n = 7), agriculture workers (n = 3), students (n = 3), and general laborers (n = 5). These data indicated that an enzootic strain of VEE virus was the cause of at least 3% (18 of 598) of the cases of febrile illnesses studied in the city of Iquitos in the Amazon Basin region of Peru. |
9452290 | Identification and genetic analysis of Panama-genotype Venezuelan equine encephalitis virus subtype ID in Peru. | Venezuelan equine encephalitis (VEE) virus was isolated in 1993, 1994, and 1995 from human cases of acute, undifferentiated, febrile illness in the Peruvian Amazon Basin. Two virus isolates were recovered in 1994 from Peruvian soldiers at a jungle outpost near Pantoja in northern Peru, and 10 isolates were obtained from military personnel and civilians in 1993-1995 in Iquitos, an urban center in northeastern Peru. The genetic relationship of these isolates to other VEE virus strains was determined by sequencing 856-867 nucleotide reverse transcription-polymerase chain reaction fragments derived from the PE2 glycoprotein gene. The sequences pared with those of other VEE virus strains, including representatives of the IAB, IC, ID, IE, II, and IIIC subtypes. The two Pantoja isolates were most closely related to subtype IC and ID viruses previously isolated in Colombia and Venezuela, and to the ID viruses isolated during the 1970s in Iquitos. All of the recent Iquitos isolates were similar to one another, but they were more closely related to Panamanian ID strains than to isolates previously obtained in Iquitos, Peru, or in Colombia and Venezuela. The recent Iquitos VEE viral isolates were the first Panama-genotype VEE ID virus strains identified outside of the Republic of Panama. |
9452291 | Seroprevalence of lymphocytic choriomeningitis virus in Nova Scotia. | An ELISA system was used to determine the rate of seropositivity to lymphocytic choriomeningitis virus (LCMV) among a random sample of 505 Nova Scotians. Twenty (4%) were positive. Complete questionnaire data were available on all 20 seropositive subjects and on 449 seronegative subjects. Seventeen (85%) of the seropositive subjects were females (P = 0.03). It is concluded that infection with LCMV is present in Nova Scotia and females are more likely to be infected than males. |
9452292 | High Cryptosporidium prevalences in healthy Aymara children from the northern Bolivian Altiplano. | The prevalence of Cryptosporidium infection was determined in four munities in the Bolivian Altiplano, between the city of La Paz and Lake Titicaca, at an altitude of 3,800-4,200 meters. Single stool specimens were randomly collected from 377 5-19-year-old students, all apparently asymptomatic. The total prevalence (31.6%) is possibly the highest reported among healthy humans (a maximum of 9.8% and 2.0% in coprologic surveys in underdeveloped and developed countries, respectively) and one of the highest even in symptomatic subjects. No significant age and sex differences were observed. Such an infection prevalence is probably related to the poor sanitation conditions, contaminated water supplies, overcrowding, and close contact with domestic animals. Continuous exposure to the parasite could be associated with protection against parasite-related symptoms in the children examined. |
9452293 | Odor-mediated host preferences of West African mosquitoes, with particular reference to malaria vectors. | The role of odors in mosquito host preferences was studied in a village near Ouagadougou, Burkina Faso. Two odor-baited entry-traps were put beside one another and a choice of host odor-laden air was blown out of them. Odors of a human and a calf (of similar mass) were drawn from two tents in which each was separately concealed. Allowances were made for trap position, differences in human-subject attractiveness, CO2 levels, and trap contamination with alternative host odors. Choices for the human-baited trap greater than the 0.5 random expectation were made by Anopheles gambiae s.l. (0.96) and An. pharoensis (0.68). The choices for the human-baited trap of Culex antennatus were significantly lower than 0.5 (0.25), whereas for the Cx. decens species group (0.56), the difference was not significant. Interpretation of the latter result plicated by the significant effect of CO2 levels on the index. Species caught in low numbers but whose trap distribution showed a bias towards the human-baited trap were An. funestus (total numbers in the human-baited trap to the calf-baited trap = 9:0), Mansonia africana (17: 1), Aedes dalzieli (22:4), and Ae. hirsutus (13:1); species showing bias towards the calf-baited trap were An. rufipes (0:11), Cx. duttoni (0:17), and Cx. nebulosus (2:35). Mansonia uniformis was the only species distributed randomly between the two traps. Molecular identification of the An. gambiae s.l. samples revealed a marked difference in trap distribution: for the human-baited trap the ratio was 52% An. arabiensis to 48% An. gambiae s.s.; for the calf-baited trap, it was 92% An. arabiensis to 8% An. gambiae s.s. |
9452294 | Microgeographic genetic differentiation of Anopheles gambiae mosquitoes from Asembo Bay, western Kenya: a comparison with Kilifi in coastal Kenya. | Microgeographic differentiation in Anopheles gambiae from seven villages less than 10 km apart in Asembo Bay, western Kenya was estimated by analysis of variability in seven microsatellite loci. Results from the Asembo Bay villages pared with specimens collected in Kilifi, coastal Kenya, 700 km to the east. Allele frequency distribution was very similar in all villages in Asembo Bay, but differed for the Kilifi population. Genetic differentiation among villages was low with loci-specific Fst falling within the range of 0.0000-0.0085. These low estimates of differentiation correspond to among-village migration indices greater than 5.66, suggesting a high level of gene flow within the Asembo population. The Nm value between Kilifi and Asembo Bay was 1.54, indicating much lower levels of gene flow. Average observed heterozygosity among the seven villages was in all but one case less than the expected heterozygosity, most likely indicating the presence of null alleles, but possibly the presence of randomly mating units (demes) smaller than the village. We conclude that there is likely no genetic structure at the level of the village in Asembo Bay but that gene flow is restricted between western and coastal Kenya, probably by the high elevation rift. |
9452295 | Intraspecific isozyme polymorphism of Anopheles gambiae in relation to environment, behavior, and malaria transmission in southwestern Burkina Faso. | A cellulose acetate electrophoresis system was used to study the isozyme polymorphism of the Anopheles plex in a rural village and a city in southwestern Burkina Faso. In both areas A. gambiae Giles was the dominant species (95%) whereas A. arabiensis Patton represented only 5%. Both species were separated readily by octanol dehydrogenase Odh and mannose phosphate isomerase (Mpi) even if they shared some alleles at these two loci. Polymorphism analysis (13 loci) at the intraspecific level of A. gambiae showed a significant difference between the specimens collected in the city from those collected in the village in their allelic and genotypic frequencies of isocitrate dehydrogenase-1 and malate dehydrogenase-1 and in their allelic frequencies for Mpi. No genetic difference was observed between the human biting A. gambiae collected inside or outside the houses in either the village or the city. The Plasmodium falciparum-infected A. gambiae differed from the noninfected ones in their allelic and genotypic frequencies at Mpi and acid phosphatase (Acp). A two-fold difference in infection rate was found for the genotype Mpi130/130 and pared with other genotypes. However, infected anophelines were found in all genotypes that belonged to these two enzyme systems. Consequently, no refractory mechanism occurs in these natural populations. |
9452296 | Testing for anti-circumsporozoite and anti-blood-stage antibodies for epidemiologic assessment of Plasmodium falciparum infection in travelers. | The purpose of this investigation was to assess the role of serology for establishing incidences of Plasmodium falciparum malaria and of exposure to P. falciparum in epidemiologic studies of travelers using chemoprophylaxis. The design was a prospective cohort study involving 548 short-term Dutch travelers to areas endemic for P. falciparum malaria. Sera were collected before departure and, together with the medical history, 2-6 weeks after return. All sera were tested for anti-circumsporozoite (CS) antibodies by an R32tet32-ELISA; sera of subjects reporting febrile illness during travel or after return or with anti-CS responses were tested for anti-blood-stage antibodies by an indirect fluorescence antibody test (IFAT). Five subjects (0.9%) reported P. falciparum malaria confirmed by thick blood smear examination (documented cases) and six (1.0%) reported treatment for malaria without a documented diagnosis (presumptive cases). Conversions in the IFAT were detected in six subjects, including all five documented cases and one presumptive case. Anti-CS antibodies were detected in seven subjects (1.3%), including three documented cases and four of 442 subjects with no history of fever or malaria treatment (0.9%). Incidence rates per 1,000 person-months of travel (95% confidence interval) of infection with P. falciparum, whether or not suppressed by chemoprophylaxis, were 16.9 (8-31) for all destinations and 91.6 (33-200) for West Africa. In epidemiologic studies of P. falciparum malaria in travelers, testing for antibodies to blood stages can increase the sensitivity and specificity of case detection; testing for antibodies to sporozoites may be useful for the assessment of exposure to P. falciparum in travelers using chemoprophylaxis, but the sensitivity is limited. |
9452297 | Natural polymorphism in the thrombospondin-related adhesive protein of Plasmodium falciparum. | We have developed a typing system using natural sequence variation in the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum. This method permits a haplotype to be assigned to any particular TRAP gene. We have applied this method to a hospital-based, case control-study in Mali. Previous sequence variation and conservation in TRAP has been confirmed. Particular TRAP haplotypes can be used as geographic hallmarks. Because of the high level of conflict between characters, we have examined the phylogenetic relationships between parasites using a network approach. Having received patient samples from urban and periurban areas of Bamako, the majority of haplotypes were closely related and distinct from TRAP sequences present in other continents. This suggests that the structure of TRAP can only tolerate a limited number of sequence variations to preserve its function but that this is sufficient to allow the parasite to evade the host's immune system until a long-lived immune response can be maintained. It may also reflect host genetics in that certain variants may escape the host immune response more efficiently than others. For vaccine design, sequences from the major regional variants may need to be considered in the production of effective subunit vaccines. |