Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and Mineral Research (2004).
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Adolescent↗
Biomedical subjects
Ikuko Tanaka
Publications and source records attributed to Ikuko Tanaka.
[Corticosteroids].
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Adaptor Proteins, Signal Transducing↗
Anthraquinone polyamines: novel channel blockers to study N-methyl-D-aspartate receptors.
The effects of various anthraquinone polyamines (AQP) were studied at recombinant N-methyl-d-aspartate (NMDA) receptors expressed in Xenopus laevis oocytes. The AQP derivatives had different numbers of methylene groups between the NH(2) (or NH) groups in their spermidine-like tail. Thus, we termed these derivatives AQ33, AQ34, etc. All AQP derivatives inhibited responses of NR1/NR2 receptors in oocytes voltage-clamped at -70 mV, with IC(50) values between 4 and 22 microM. The block was strongly voltage-dependent. AQ34 and AQ33b inhibited responses of NR1/NR2 receptors but did not inhibit responses of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors expressed from GluR1 or GluR2(Q), indicating that AQ34 and AQ33b are preferential NMDA antagonists. Results of experiments using mutant NR1 and NR2 subunits identified residues that influence block by AQ34 and AQ33b. These residues are located in the outer vestibule at the selectivity filter/narrowest constriction of the channel and in the inner vestibule below the level of the selectivity filter. The results with mutant NR1 and NR2 subunits are consistent with the idea that NR1(Asn616) and NR2B(Asn616), but not NR2B(Asn615), make the narrowest constriction of NMDA channel.
Amino Acids↗
Overall distribution of GLYT2 mRNA-containing versus GAD67 mRNA-containing neurons and colocalization of both mRNAs in midbrain, pons, and cerebellum in rats.
We aimed to clarify the overall distribution of glycinergic neurons in the midbrain, pons, and cerebellum in rats, using in situ hybridization for mRNA encoding glycine transporter 2 (GLYT2), which reliably detects glycinergic cell bodies. We combined this method with in situ hybridization for mRNA encoding glutamic acid decarboxylase isoform 67 (GAD67), and have presented for the first time global and detailed views of the distribution of glycinergic neurons in relation to GABAergic neurons. In addition to this single-detection study, we performed double-detection of GLYT2 mRNA and GAD67 mRNA to determine the distribution of neurons co-expressing these mRNAs. We have shown that many areas of the brainstem and cerebellum, not only areas where previous immunohistochemical studies have specified, involve double-labeled neurons with GLYT2 and GAD67 mRNAs. In particular, when lightly labeled GLYT2 mRNA-positive neurons were distributed within the area of GAD67 mRNA-positive neurons, almost all such GLYT2 mRNA-positive neurons were GAD67 mRNA-positive. Areas or neuron groups expressing exclusively GLYT2 mRNA or GAD67 mRNA were rather limited, such as the superior colliculus, nucleus of the trapezoid body, and Purkinje cells. The present study suggests that the corelease of glycine and GABA from single neurons is more widespread than has been reported.
Amino Acid Transport Systems, Neutral↗
Clinicopathological correlation of childhood IgA glomerulonephritis presenting diffuse endocapillary proliferation.
The aim of the present study is to clarify the clinicopathological correlation of childhood IgA glomerulonephritis (GN) presenting diffuse endocapillary proliferation. Twenty-seven patients were used in the present study. The 27 patients were divided into three groups (mild, moderate and severe) according to the percentage of glomeruli displaying global endocapillary proliferation per total glomeruli at the first biopsy. The degree of both cellular crescent and lysis of the glomerular basement membrane (GBM) at the first biopsy was semiquantitatively evaluated. The degree of cellular crescent and lysis in the GBM was greater in the severe group than in the mild group. The degree of lysis of the GBM positively correlated with the degree of distribution of endocapillary proliferation. The degree of glomerular sclerosis at the second biopsy was greater in the severe group compared with the other two groups. The severity of cellular crescent at the first biopsy positively correlated with that of glomerular sclerosis at the second biopsy. Multiple logistic regression analysis indicated that the risk of glomerular sclerosis at the second biopsy was 19-fold higher in the odds ratio in the severe group compared with the mild group. In conclusion, the progression of glomerular sclerosis in serial biopsy is dependent on the degree of distribution of endocapillary proliferation and the severity of cellular crescents at the first biopsy in childhood IgA GN presenting diffuse endocapillary proliferation.
Adolescent↗
[Recommendations for the diagnosis and treatment of glucocorticoid-induced osteoporosis].
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Bone Density↗
[Glucocorticoid-induced osteoporosis and bone mineral densimetry].
While the diagnosis and management of primary osteoporosis have been established and widely utilized, these for glucocorticoid-induced osteoporosis (GIOP), i.e. a representative of secondary osteoporosis, are on their way. GIOP caused fractures at a higher bone mineral density (BMD) compared to primary osteoporosis. The cut off value of the BMD for prediction of fractures was around 80% of the young adult means (T-score; -1.5). As this value would give a useful diagnostic point for initiating treatments, measurements of BMD should be a significant tool for management of GIOP.
Absorptiometry, Photon↗
Glycine is used as a transmitter by decrementing expiratory neurons of the ventrolateral medulla in the rat.
The medullary respiratory network involves various types of respiratory neurons. The present study focused on possible inhibitory neurons called decrementing expiratory (E-DEC) neurons and aimed to determine whether their transmitter is glycine or GABA. In Nembutal-anesthetized, neuromuscularly blocked, and artificially ventilated rats we labeled E-DEC neurons with Neurobiotin and processed the tissues for detection of mRNA encoding either glycine transporter 2 (GLYT2) as a marker for glycinergic neurons or glutamic acid decarboxylase isoform 67 (GAD67) as a marker for GABAergic neurons, using in situ hybridization. Of 38 E-DEC neurons that were labeled, cranial motoneurons (n = 14), which were labeled as control, were negative for either GLYT2 mRNA (n = 10) or GAD67 mRNA (n = 4). The other E-DEC neurons (n = 24) were non-motoneurons. Sixteen of them were examined for GLYT2 mRNA, and the majority (11 of 16) was GLYT2 mRNA-positive. The remaining E-DEC neurons (n = 8) were examined for GAD67 mRNA, and all of them were GAD67 mRNA-negative. The GLYT2 mRNA-positive E-DEC neurons were located in the ventrolateral medulla spanning the Bötzinger complex (BOT), the rostral ventral respiratory group (VRG), and the caudal VRG. We conclude that not only E-DEC neurons of the BOT but also many E-DEC neurons of the VRG are inhibitory and use glycine as a transmitter. Although the present negative data cannot rule out completely the release of GABA or co-release of glycine and GABA from E-DEC neurons, several lines of evidence suggest that the glycinergic process is primarily responsible for the phasic inhibition of the respiratory network during the expiratory phase.
Amino Acid Transport Systems, Neutral↗
Activity of brainstem respiratory neurones just before the expiration-inspiration transition in the rat.
Inspiratory activity of the hypoglossal nerve (XIIn) often precedes that of the phrenic nerve (PHRn). By manipulating artificial respiration, this preceding activity (pre-I XIIn activity) can be lengthened or isolated prematurely (decoupled XIIn activity) without developing into overt PHRn-associated inspiratory bursts. We hypothesized that these pre-I and decoupled XIIn activities, collectively termed 'XIIn-w/o-PHRn activity', reflect certain internal states of the respiratory centre at the period just prior to the transition from the expiratory phase to the inspiratory phase. In decerebrate, neuromuscularly blocked and artificially ventilated rats, the firing properties of medullary respiratory neurones were examined during the period of the XIIn-w/o-PHRn activity. The majority of the inspiratory neurones examined could be classified into two types: one was active (XIIn-type) and the other was inactive (PHRn-type) during the XIIn-w/o-PHRn period. On the other hand, augmenting expiratory (E-AUG) neurones of the Bötzinger complex (BOT) and the caudal ventral respiratory group (VRG) fired intensively during this period. Their firing stopped at the onset of the overt inspiratory bursts in the XIIn and PHRn, suggesting that BOT E-AUG neurones inhibit PHRn-type, but not XIIn-type, inspiratory neurones. We hypothesize that XIIn-type inspiratory activity facilitates the phase change from expiration to inspiration, through activation of certain inspiratory neurones that inhibit the firing of BOT E-AUG neurones and generation of the overt inspiratory bursts in XIIn-type and PHRn-type inspiratory neurones.
Animals↗
Brainstem and spinal projections of augmenting expiratory neurons in the rat.
There are two types of expiratory neurons with augmenting firing patterns (E-AUG neurons), those in the Bötzinger complex (BOT) and those in the caudal ventral respiratory group (cVRG). We studied their axonal projections morphologically using intracellular labeling of single E-AUG neurons with Neurobiotin, in anesthetized, paralyzed and artificially-ventilated rats. BOT E-AUG neurons (n = 11) had extensive axonal projections to the brainstem, but E-AUG neurons (n = 5) of the cVRG sent axons that descended the contralateral spinal cord without medullary collaterals. In addition to these somewhat expected characteristics, the present study revealed a number of new projection patterns of the BOT E-AUG neurons. First, as compared with the dense projections to the ipsilateral brainstem, those to the contralateral side were sparse. Second, several BOT E-AUG neurons sent long ascending collaterals to the pons, which included an axon that reached the ipsilateral parabrachial and Kölliker-Fuse nuclei and distributed boutons. Third, conspicuous projections from branches of these ascending collaterals to the area dorsolateral to the facial nucleus were found. Thus, the present study has shown an anatomical substrate for the extensive inhibitory projections of single BOT E-AUG neurons to the areas spanning the bilateral medulla and the pons.
Animals↗
Distribution of glycine transporter 2 mRNA-containing neurons in relation to glutamic acid decarboxylase mRNA-containing neurons in rat medulla.
We studied the distribution of medullary glycinergic neurons in relation to GABAergic neurons, by using in situ hybridization method for mRNA encoding either glycine transporter 2 (GLYT2) or glutamic acid decarboxylase isoform 67 (GAD67). GLYT2 mRNA-positive (GLYT2+) neurons were distributed widely and clustered in (1). the respiration-related area of the ventrolateral medulla called the Bötzinger complex, (2). the nucleus retroambiguus caudal to the obex or the caudal ventral respiratory group, (3). the spinal trigeminal nucleus, (4). a small area immediately dorsal to the inferior olivary nucleus, and (5). the border zone between the hypoglossal nucleus and the surrounding reticular formation. It was characteristic that in the dorsomedial medulla, GLYT2+ neurons were distributed only sparsely in contrast to dense GAD67+ neurons. Only few GLYT2+ neurons were distributed in the medial and interstitial subnuclei of the nucleus tractus solitarii. In particular virtually no GLYT2+ neurons were found in the area postrema. Furthermore, in the reticular formation and the spinal trigeminal nucleus, GAG67+ neurons tended to be distributed in the area where GLYT2+ neurons were sparse, and vice versa. These results provide useful information for the effort of determining neurotransmitters involved in the medullary neurons.
Amino Acid Transport Systems, Neutral↗
Activity of neurons in ventrolateral respiratory groups during swallowing in decerebrate rats.
To elucidate the neuronal basis of the coordination between swallowing and respiration, we examined the swallowing-related activity of respiratory neurons in the ventrolateral respiratory groups of the medulla oblongata of decerebrate, paralyzed and artificially ventilated rats (n = 14). Extracellular recording was made during fictive swallowing evoked by the electrical stimulation of the superior laryngeal nerve from a total of 141 neurons with respiratory rhythm (99 expiratory and 42 inspiratory neurons). The burst of discharge by the hypoglossal nerve was used to monitor the pharyngeal phase of swallowing. The decrementing-expiratory (E-DEC) neurons (n = 62) were activated during (n = 46) or after (n = 10) the hypoglossal bursts, or showed no swallowing-related activity (n = 6). All of the augmenting-expiratory (E-AUG) neurons (n = 37) were silent during the hypoglossal bursts but were activated after each swallow. Inspiratory neurons showed either no swallowing-related bursts (n = 27), or were activated after the hypoglossal bursts (n = 15). Activation of the majority of E-DEC neurons may be related to the arrest of respiration during swallowing, and the post-swallow activation of E-AUG neurons may correspond to the expiratory phase that follows swallowing. We suggest that these behaviors of expiratory neurons are essential in the phase resetting of the respiratory cycle in association with the swallowing.
Animals↗
[Glucocorticoid-induced osteoporosis, up to date].
Glucocorticoid-induced osteoporosis (GIO) has been a hot topic in recent years. Glucocorticoids (GC) increase a fracture risk depending on the doses and affected especially vertebral bones. After cessation of GC, the fracture risk falls promptly, but does not reach at an equivalent level to non-medication. Moreover, a threshold of bone mineral densities predicting a fracture is higher in GIO than that in post-menopausal osteoporosis. Renewal of the management for GIO from UK is based on new knowledge. Risk factors other than bone mineral densities have been taken into consideration in renewing the management. An original management plan in Japan is expected coming soon. Further development of future research is needed.
English Abstract↗
Intracellular activity of superior laryngeal nerve motoneurons during fictive swallowing in decerebrate rats.
We examined the swallowing-related intracellular activity of motoneurons of the superior laryngeal nerve (SLN) in decerebrate, paralyzed and artificially-ventilated rats, to elucidate the neuronal mechanism of the pharyngo-esophageal and laryngo-esophageal coordination during swallowing. The majority of the SLN motoneurons exhibited respiratory rhythm (n=16; 13 inspiratory, one expiratory and two non-respiratory neurons). During fictive swallowing evoked by electrical stimulation of the SLN, all these motoneurons showed a hyperpolarization-depolarization sequence in their membrane potentials. The hyperpolarization, which was shown to consist of inhibitory postsynaptic potentials, started at the onset of the hypoglossal swallowing burst, lasted during the burst, and was followed by a depolarization at the end of the burst. This hyperpolarization-depolarization pattern implies that the SLN motoneurons may be involved in the 'inhibitory chain' within the swallowing pattern generator, which may be cardinal in the sequential activation of different populations of motoneurons innervating the swallowing-related muscles.
Action Potentials↗
Difference between hypoglossal and phrenic activities during lung inflation and swallowing in the rat.
We aimed in this study to elucidate the discharge properties and neuronal mechanisms of the dissociation between hypoglossal and phrenic inspiratory activities in decerebrate rats, which had been subjected to neuromuscular blockade and artificially ventilated. The discharge of the hypoglossal nerve and the intracellular activity of hypoglossal motoneurones were monitored during respiration and fictive-swallowing evoked by electrical stimulation of the superior laryngeal nerve, and were compared with the activity of the phrenic nerve. The hypoglossal nerve activity was characterized by its onset preceding the phrenic nerve activity ('pre-I' activity). By manipulating artificial respiration, we could augment the 'pre-I' activity, and could elicit another type of hypoglossal activity decoupled from the phrenic-associated inspiratory bursts ('decoupled' activity). We further scrutinized the correlatives of 'pre-I' and 'decoupled' activities in individual hypoglossal motoneurones. Hypoglossal motoneurones consisted of inspiratory (n = 42), expiratory (n = 18) and non-respiratory (n = 1) neurones and were classified by their swallowing activity into depolarized, hyperpolarized, hyperpolarized-depolarized and unresponsive groups. All of the inspiratory neurones were depolarized in accordance with the 'pre-I' and 'decoupled' activities, and all of the expiratory neurones were hyperpolarized during these activities. Fictive swallowing, which was characterized by its frequent emergence just after the phrenic inspiratory activity, was also evoked just after the 'decoupled' hypoglossal activity, suggesting that this activity may have similar effects on swallowing as the 'overt' inspiratory activity. Such a coupling between 'decoupled' and swallowing activities was also revealed in each motoneurone. These findings suggest that the 'pre-I' and 'decoupled' activities may reflect some internal inspiratory activity of the respiratory centre and that hypoglossal motoneurones may be driven by a distinct group of premotor neurones that possibly play a role in the coordination of respiration and swallowing.
Animals↗
Swallowing-related activities of respiratory and non-respiratory neurons in the nucleus of solitary tract in the rat.
Swallowing-related activity was examined in respiratory (n = 60) and non-respiratory (n = 82) neurons that were located in and around the nucleus of the solitary tract (NTS) in decerebrated, neuromuscularly blocked and artificially ventilated rats. Neurons that were orthodromically activated by electrical stimulation of the superior laryngeal nerve (SLN) were identified, and fictive swallowing was evoked by SLN stimulation. The pharyngeal phase of swallowing was monitored by hypoglossal nerve activity. Two types of non-respiratory neurons with swallowing-related bursts were identified: 'early' swallowing neurons (n = 24) fired during periods of hypoglossal bursts, and 'late' swallowing neurons (n = 8) fired after the end of hypoglossal bursts. The remaining non-respiratory neurons were either suppressed (n = 21) or showed no change in activity (n = 29) during swallowing. On the other hand, respiratory neurons with SLN inputs included 56 inspiratory and four expiratory neurons. Inspiratory neurons were classified into two major types: a group of neurons discharged simultaneously with hypoglossal bursts (type 1 neurons, n = 19), while others were silent during bursts but were active during inter-hypoglossal bursts when swallowing was provoked repetitively (type 2 neurons, n = 34). Three of the expiratory neurons fired during hypoglossal bursts. Many of the swallowing-related non-respiratory neurons and the majority of the inspiratory neurons received presumed monosynaptic inputs from the SLN. Details of the distribution and firing patterns of these NTS neurons, which have been revealed for the first time in a fictive swallowing preparation in the rat, suggest their participation in the initiation, pattern formation and mutual inhibition between swallowing and respiration.
Animals↗
Axonal projections of pulmonary slowly adapting receptor relay neurons in the rat.
We elucidated efferent projections of second-order relay neurons (P-cells) activated by afferents originating from slowly adapting pulmonary receptors (SARs) to determine the central pathway of the SAR-evoked reflexes. Special attention was paid to visualizing the P-cell projections within the nucleus tractus solitarii (NTS), which may correspond to the inhibitory pathway from P-cells to second-order relay neurons (RAR-cells) of rapidly adapting pulmonary receptors. P-cells were recorded from the NTS in Nembutal-anesthetized, paralyzed, and artificially ventilated rats. First, we used electrophysiological methods of antidromic mapping and showed that the majority of the P-cells examined projected their axons to the caudal NTS and to the dorsolateral pons corresponding to the parabrachial complex. Second, a mixture of HRP and Neurobiotin was injected intracellularly or juxtramembranously into P-cells. (1) Stained P-cells (n = 7) were located laterally to the solitary tract and had dendrites extending characteristically along the lateral border of the solitary tract. (2) All P-cells had stem axons projecting to the ipsilateral medulla. Of these, the axons from five P-cells projected to the nucleus ambiguus and its vicinity with distributing boutons. Some of these axons further ascended in the ventrolateral medulla, and distributed boutons in the areas ventral or ventrolateral to the nucleus ambiguus. (3) All the P-cells had axonal branches with boutons in the NTS area. In particular, axons from three P-cells projected bilaterally to the medial NTS caudal to the obex, i.e., to the area of RAR-cells. These results show anatomic substrates for the connections implicated in the P-cell inhibition of RAR-cells as well as the SAR-induced respiratory reflexes.
Action Potentials↗
Morphology of the decrementing expiratory neurons in the brainstem of the rat.
In anesthetized and artificially-ventilated rats, the morphological properties of decrementing expiratory (E-DEC) neurons were studied using intracellular recording and labeling with Neurobiotin. Sixteen E-DEC neurons were successfully labeled; ten of which were cranial motoneurons located in the facial (FN) and ambiguus (NA) nuclei. Two interneurons were labeled in the Bötzinger complex (BOT) and the ventral respiratory group (VRG) rostral to the obex, and the remaining four in the VRG caudal to the obex. All the interneurons had extensive intramedullary collaterals within the ventrolateral medulla. Terminal-like boutons were distributed ventral to the NA at the level of the BOT, both ventral to and within the NA at the level rostral to the obex and largely within the cell column tentatively designed as the ambiguous-retroambiguus complex (NA/NRA) caudal to the obex. The four interneurons in the NA/NRA had axons projecting to the spinal cord as well. The extensive intramedullary projections suggest that these E-DEC interneurons of the BOT and the VRG play a significant role in respiration. The simultaneous projections from the caudal E-DEC neurons to both the spinal cord and the NA suggest that these neurons also play integrative roles in non-respiratory behaviors including vocalization, swallowing and defecation.
Animals↗