Search PubMed⌕ Search

Biomedical subjects

N Fujiki

Publications and source records attributed to N Fujiki.

At least 19 recordsLinked to original sources
PubMed2001

CSF hypocretin/orexin levels in narcolepsy and other neurological conditions.

OBJECTIVE: To examine the specificity of low CSF hypocretin-1 levels in narcolepsy and explore the potential role of hypocretins in other neurologic disorders. METHODS: A method to measure hypocretin-1 in 100 microL of crude CSF sample was established and validated. CSF hypocretin-1 was measured in 42 narcolepsy patients (ages 16-70 years), 48 healthy controls (ages 22-77 years,) and 235 patients with various other neurologic conditions (ages 0-85 years). RESULTS: As previously reported, CSF hypocretin-1 levels were undetectably low (<100 pg/mL) in 37 of 42 narcolepsy subjects. Hypocretin-1 levels were detectable in all controls (224-653 pg/mL) and all neurologic patients (117-720 pg/mL), with the exception of three patients with Guillain-Barré syndrome (GBS). Hypocretin-1 was within the control range in most neurologic patients tested, including patients with AD, PD, and MS. Low but detectable levels (100-194 pg/mL) were found in a subset of patients with acute lymphocytic leukemia, intracranial tumors, craniocerebral trauma, CNS infections, and GBS. CONCLUSIONS: Undetectable CSF hypocretin-1 levels are highly specific to narcolepsy and rare cases of GBS. Measuring hypocretin-1 levels in the CSF of patients suspected of narcolepsy is a useful diagnostic procedure. Low hypocretin levels are also observed in a large range of neurologic conditions, most strikingly in subjects with head trauma. These alterations may reflect focal lesions in the hypothalamus, destruction of the blood brain barrier, or transient or chronic hypofunction of the hypothalamus. Future research in this area is needed to establish functional significance.

Carrier Proteins↗
PubMed2001

Decreased brain histamine content in hypocretin/orexin receptor-2 mutated narcoleptic dogs.

A growing amount of evidence suggests that a deficiency in hypocretin/orexin neurotransmission is critically involved in animal and human forms of narcolepsy. Since hypocretin-containing neurons innervate and excite histaminergic tuberomammillary neurons, altered histaminergic neurotransmission may also be involved in narcolepsy. We found a significant decrease in histamine content in the cortex and thalamus, two structures important for histamine-mediated cortical arousal, in Hcrtr-2 mutated narcoleptic Dobermans. In contrast, dopamine and norepinephrine contents in these structures were elevated in narcoleptic animals, a finding consistent with our hypothesis of altered catecholaminergic transmission in these animals. Considering the fact that histamine promotes wakefulness, decreases in histaminergic neurotransmission may also account for the sleep abnormalities in hypocretin-deficient narcolepsy.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

Response of renal sympathetic nerve activity to parabolic flight-induced gravitational change in conscious rats.

The renal sympathetic nerve activity (RNA) response to gravitational changes induced by parabolic flight was examined in chronically instrumented conscious rats. Two types of RNA responses were found. In six out of 12 rats, the RNA did not respond during the 2 G period, but immediately fell to background levels on entry into microgravity (microG), then recovered to the 1 G control level during continued microG (shutdown obvious group). In the other six rats, the RNA increased to 158+/-13% at the end of the 2 G period, increased further to 195+/-22% on entry into microG, then gradually recovered to that seen at 1 G (shutdown obscure group). The mean arterial pressure in the shutdown obvious group was significantly higher and the heart rate tended to be higher than in the shutdown obscure group, suggesting that the baseline sympathetic tone in the shutdown obvious group was higher than in the shutdown obscure group. These results suggest that the RNA response to parabolic flight might be affected by the baseline sympathetic tone.

Animals↗
PubMed2001

Acute response of aortic nerve activity to free drop-induced microgravity in anesthetized rats.

To test the hypothesis that arterial baroreflex was stimulated during microgravity (microG), arterial pressure (AP), intrathoracic pressure (ITP), and aortic nerve activity (ANA) were measured in anesthetized rats during 4.5 s of microG produced by free drop. A smooth and immediate reduction in G occurred during free drop, microG being achieved 100 ms after the start of the drop. Acute microG elicited an immediate and striking, but transient, increase in ANA, with no significant change in the AP, but a significant decrease in the end-expiratory ITP. The calculated transmural pressure of the aorta increased by 6.9 mmHg 2 s after the start of the drop. The increase in ANA lasted 2 s, then ANA returned to the control level, despite the calculated end-expiratory transmural pressure still being high. These results suggest that microG conditions stimulate the aortic baroreceptor by increasing transmural pressure by reducing the ITP. However, this effect is only transient, probably due to the high-pass property of the baroreceptors.

Animals↗
PubMed2001

Changes in CSF hypocretin-1 (orexin A) levels in rats across 24 hours and in response to food deprivation.

Hypocretin-1 is consistently detectable in the CSF of healthy human subjects, but is absent in narcoleptics. However, functional roles of CSF hypocretin are largely unknown. We examined fluctuation of CSF hypocretin-1 across 24 h and in response to food restriction in rats. Hypocretin-1 levels were high during the dark period when animals were active, but decreased by 40% toward the end of the light (rest) period. After 72 h food deprivation hypocretin-1 levels during the rest phase increased to concentrations similar to those seen during the baseline active phase; however, no increase in response to food deprivation was observed during the active phase. These results indicate an important link between circadian control of sleep and energy homeostasis via the hypocretin system.

Animals↗
PubMed2001

Hypocretin levels in sporadic and familial cases of canine narcolepsy.

Familial and sporadic forms of narcolepsy exist in both humans and canines. Mutations in the hypocretin receptor 2 gene (Hcrtr 2) cause canine familial narcolepsy. In humans, mutations in hypocretin-related genes are rare, but cerebrospinal fluid (CSF) hypocretin-1 is undetectable in most sporadic cases. Using the canine model, we investigated ( 1 ) whether hypocretin deficiency is involved in sporadic cases and ( 2 ) whether alterations in hypocretin neurons or ligand levels also contribute to the phenotype in Hcrtr 2 mutants. We found that hypocretins were undetectable in the brains of three of three and the CSF of two of two sporadic narcoleptic dogs tested. In contrast, hypocretin levels were not altered in brains and CSF of genetically narcoleptic Dobermans, and hypocretin-containing neurons were of normal appearance. Therefore, multiple hypocretin-related etiologies are likely to be involved in canine narcolepsy. The presence of hypocretin peptides in Hcrtr 2-mutated animals suggests that neurotransmission through Hcrtr 1 may be intact, arguing for a preferential importance of Hcrtr 2-mediated function in narcolepsy.

Age Factors↗
PubMed2001

Atlantoaxial subluxation in an adult secondary to retropharyngeal abscess.

Atlantoaxial subluxation secondary to a retropharyngeal abscess is well described in children, but very rare in adults. Only two adult cases have been reported in the literature. We present a case of severe atlantoaxial subluxation in an adult secondary to retropharyngeal abscess. His atlas-dens interval was very large, up to 10 mm in flexion. We tried external fixation with a neck collar initially, but for remaining instability, surgical fusion was performed. The mechanism of subluxation is attributed to softening of the ligament allowing greater mobility at the joint. The etiology of this process is speculative.

Atlanto-Axial Joint↗
PubMed2001

Fluctuation of extracellular hypocretin-1 (orexin A) levels in the rat in relation to the light-dark cycle and sleep-wake activities.

Hypocretins/orexins are neuropeptides implicated in sleep regulation and the sleep disorder narcolepsy. In order to examine how hypocretin activity fluctuates across 24 h with respect to the sleep-wake cycle, we measured changes in extracellular hypocretin-1 levels in the lateral hypothalamus and medial thalamus of freely moving rats with simultaneous sleep recordings. Hypocretin levels exhibited a robust diurnal fluctuation; levels slowly increased during the dark period (active phase), and decreased during the light period (rest phase). Levels were not correlated with the amount of wake or sleep in each period. Although an acute 4-h light-shift did not alter hypocretin levels, 6-h sleep deprivation significantly increased hypocretin release during the forced-wake period. Hypocretin activity is, thus, likely to build up during wakefulness and decline with the occurrence of sleep. These findings, together with the fact that a difficulty in maintaining wakefulness during the daytime is one of the primary symptoms of hypocretin-deficient narcolepsy, suggest that hypocretin activity may be critical in opposing sleep propensity during periods of prolonged wakefulness.

Animals↗
PubMed2001

Narcoleptic canines display periodic leg movements during sleep.

Periodic leg movements during sleep (PLMS) is a high prevalent sleep disorder of unknown etiology. The disease is pharmacologically treated with dopaminergic agonists (i.e. D2/D3 agonists) and opiates. Periodic leg movements during sleep often occur in narcoleptic patients. We observed that narcoleptic canines, like narcoleptic humans, also exhibit jerky, unilateral or bilateral slow leg movements during sleep. The movements in dogs are characterized by repetitive dorsiflexions of the ankle, lasting 0.5-1.5 s, and occur at regular intervals of 3-20 s, thus showing similarities to PLMS in humans. The observation that D2/D3 agonists aggravate cataplexy in narcoleptic dogs suggests that altered dopaminergic regulation in canine narcolepsy may play a critical role in both cataplexy and PLMS. Our canines may therefore be an invaluable resource in PLMS research.

Animals↗
PubMed2001

Effects of pCO(2) on the CSF turnover rate in T(1)-weighted magnetic resonance imaging.

The cerebrospinal fluid (CSF) secretion of rat was monitored by longitudinal relaxation time-weighted magnetic resonance imaging (T(1)-weighted MRI) in combination with a ventricular injection of a T(1)-relaxation reagent: gadolinium-diethylene triamine-N,N,N',N",N"-pentaacetic acid (Gd-DTPA). A cannula was inserted in the left lateral ventricle, and 5 microl of 8.5 mM Gd-DTPA was injected as a CSF marker. Changes in the image intensity of the CSF were measured every 30 s, and the turnover rate of CSF (k) in the left lateral ventricle was obtained from the dilution of Gd-DTPA, based on the assumption of a single compartment model. In the control conditions, k was 0.158 +/- 0.009 min(-1) at an arterial blood CO(2) tension (pCO(2)) of 38.6 +/- 2.2 mmHg (n = 10), which corresponds to the CSF secretion rate of 3.6 microl min(-1). The k value was decreased (0.078 +/- 0.010 min(-1), n = 4) by a carbonic-anhydrase inhibitor (acetazolamide). The turnover rate was decreased by hypocapnia (0.094 +/- 0.019 min(-1), pCO(2) = 24.7 +/- 2.9 mmHg, n = 4), and it increased gradually and reached a plateau level as a result of hypercapnia (0.194 +/- 0.011 min(-1), pCO(2) = 104.5 +/- 7.1 mmHg, n = 10). These results suggested that CO(2) upregulates the secretion of CSF in the rat.

Animals↗
PubMed2000

Role of the vestibular system in sudden shutdown of renal sympathetic nerve activity during microgravity in rats.

The purpose of this study was to examine the effect of microgravity (muG) on renal sympathetic nerve activity (RNA) in rats. Additionally, we estimated the participation of the vestibular system in the response of RNA to muG. Eight normal Sprague-Dawley (SD) rats and five chemically and bilaterally labyrinthectomied SD rats were used to measure RNA during free-drop examination (4.5-s duration of muG); arterial pressure (AP) and aortic flow velocity (AFV) were additionally monitored. Although AFV showed no particular change, AP tended to decrease during muG in the later phase. Prior to this AP fall-off, RNA was immediately and markedly attenuated by muG. This attenuation was transient and RNA returned to 1G level within the mu;muG condition. Interestingly, this phenomenon remained even in labyrinthectomied rats. In conclusion, cephalad shift of the body fluid by loading of muG may cause cardiopulmonary low-pressure receptor activation and consequent RNA attenuation, but the participation of the vestibulosympathetic reflex in this phenomenon is not obvious.

Animals↗
PubMed2000

Acute responses of renal nerve activity to microgravity induced by free drop in anesthetized rats.

To examine acute cardiovascular and autonomic responses to microgravity (microG), arterial pressure (AP), aortic flow velocity (AFV), central venous pressure (CVP), and renal nerve activity (RNA) were measured in anesthetized rats during 4.5 s of microG produced by free drop. A smooth and immediate reduction in gravity occurred during free drop, microG being achieved 100 ms after the start of the drop. Acute microG elicited an immediate and striking, but transient, decrease in RNA with no significant change in AP and AFV, but a significant decrease in CVP. The decrease in RNA lasted 2 s, then RNA recovered to the control level despite the G value remaining at < 0.001 for 4.5 s. The RNA decrease was attenuated or completely abolished by sinoaortic denervation, vagotomy, or sinoaortic denervation plus vagotomy. These results suggest that acute microG conditions stimulate sinoaortic and cardiopulmonary mechanoreceptors and suppress RNA.

Animals↗
PubMed2000

Increased cortical activation during hearing of speech in cochlear implant users.

To investigate the cortical activities while listening to noise and speech in cochlear implant (CI) users, we compared cerebral blood flow in postlingually deafened CI users with that in normal hearing subjects using positron emission tomography. While noise activation in CI users did not significantly differ from that in normal subjects, hearing speech activated more cortical areas in CI users than in normal subjects. A comparison of speech activation in these two groups revealed higher activation in CI users not only in the temporal cortices but also in Broca's area and its right hemisphere homologue, the supplementary motor area and the anterior cingulate gyrus. In postlingually deafened subjects, the hearing of speech coded by CI may be accompanied by increased activation of both the temporal and frontal cortices.

Adult↗
PubMed2000

Functional differentiation of the auditory association area in prelingually deaf subjects.

BACKGROUND: it is believed that the number of neurons of the human cortex increases rapidly in the first postnatal year, and then decreases gradually towards adult level as their functions are revised up to 11 years of age ('synaptic revision'). It is also confirmed that regional cerebral blood flow (rCBF) at rest represents the density of the neurons and decreases in accordance with the synaptic revision in process. If synaptic revision does not occur, rCBF remains at high level. Thus, we can evaluate whether functional differentiation has occurred in the human cortex by measuring rCBF at resting state. OBJECTIVE: to examine functional differentiation of the auditory association area (A2) in prelingually deaf subjects. METHODS: six postlingually and six prelingually deaf subjects who had undergone cochlear implant (CI) were involved in the current study. All prelingually deaf subjects underwent CI over 8 years old. The rCBF in A2 was examined during resting and listening to speech sounds using positron emission tomography (PET) and H2(15)O intravenous injection. Twelve normal subjects' rCBFs were also measured as control. Furthermore, three prelingually deaf subjects underwent follow up PET studies in which cortical activities in A2 for listening and lipreading were examined. RESULTS: in the examination of rCBF at rest, rCBFs of prelingually deaf subjects in A2 showed significantly higher than those of either the postlingually deaf subjects or normal subjects. During listening, rCBFs in A2 increased in postlingually deaf subjects and normal subjects, while there was no significant rCBF increase in the prelingually deaf. High rCBF level in A2 at rest observed in prelingually deaf subjects implied a lack of synaptic revision, and it was suggested that the functional differentiation for auditory processing was little in the A2 of prelingually deaf subjects. In the follow up study for three prelingually deaf subjects, activation of A2 was observed during lipreading but not during listening in two cases, who had developed the skill of lipreading while speech recognition was not improved by CI. In contrast, the other case had not used any visual clues in daily communication prior to CI, and the hearing acuity was well improved by CI. This case demonstrated an activity in A2 during listening, while lipreading induced no activation. CONCLUSION: it is suggested that functional differentiation of A2 should differ according to which of visual and auditory clue is chiefly used during critical periods for speech acquisition. The findings are thought to be important for us to schedule the education and treatment for prelingually deaf children.

Adolescent↗
PubMed2000

Hepatoportal bumetanide-sensitive K(+)-sensor mechanism controls urinary K(+) excretion.

To determine whether a K(+)-sensor mechanism exists in the hepatoportal region, periarterial hepatic afferent nerve activity responses to intraportal injection of KCl were examined in anesthetized rats. Hepatic afferent nerve activity increased in response to intraportal injection in a K(+) concentration-dependent manner, and the increase was attenuated by inhibition of the Na(+)-K(+)-2Cl(-) cotransporter by bumetanide in a dose-dependent manner. These results suggest that a bumetanide-sensitive K(+)-sensor mechanism exists in the hepatoportal region. Stimulation of this mechanism by intraportal KCl infusion elicited an immediate and powerful kaliuresis with no significant change in the plasma K(+) concentration; this was significantly greater than the kaliuresis induced by intravenous KCl infusion and was attenuated by severing the periarterial hepatic nervous plexus. These results indicate that a hepatoportal bumetanide-sensitive K(+)-sensor mechanism senses the portal venous K(+) concentration and that stimulation of this sensor mechanism causes kaliuresis, which is mainly mediated by the periarterial hepatic nervous plexus.

Afferent Pathways↗