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Biomedical subjects

N Hori

Publications and source records attributed to N Hori.

At least 37 records · Page 2Linked to original sources

Incidence of adverse reactions associated with acupuncture.

OBJECTIVES: To determine the type, severity, and incidence of acupuncture adverse reactions that are observed in standard practice. DESIGN: A survey based on observation and interview by the therapists. SETTING: Tsukuba College of Technology Clinic in Japan. SUBJECTS: All patients who underwent acupuncture treatment during a period of 4 months from April to July 1998. OUTCOME MEASURES: Type, severity, and incidence of acupuncture adverse reactions. RESULTS: A total of 391 patients were treated in 1,441 sessions, involving a total of 30,338 needle insertions. The incidence of recorded systemic reactions in individual patients was: tiredness (8.2%); drowsiness (2.8%); aggravation of preexisting symptoms (2.8%); itching in the punctured regions (1.0%); dizziness or vertigo (0.8%); feeling of faintness or nausea during treatment (0.8%); headache (0.5%); and chest pain (0.3%). The incidence of recorded local reactions, expressed as a percentage of needle insertions, was: minor bleeding on withdrawal of the needle (2.6%); pain on insertion of the needle (0.7%); petechia or ecchymosis (0.3%); pain or ache in the punctured region after the treatment (0.1%); subcutaneous haematoma (0.1%); and pain or discomfort in the punctured region during the needle retention (0.03%). CONCLUSION: Although some adverse reactions associated with acupuncture were common even in standard practice, they were transient and mild compared to cases such as pneumothorax, cardiac injury, infection, or spinal lesions reported in other studies.

Acupuncture Therapy↗

BodyMap: a collection of 3' ESTs for analysis of human gene expression information.

BodyMap is a collection of site-directed 3' expressed sequence tags (ESTs) (gene signatures, GSs) that contains the transcript compositions of various human tissues and was the first systematic effort to acquire gene expression data. For the construction of BodyMap, cDNA libraries were made, preserving abundance information and histologic resolutions of tissue mRNAs. By sequencing 164,000 randomly selected clones, 88,587 GSs that represent chromosomally coded transcripts have been collected from 51 human organs and tissues. They were clustered into 18,722 independent 3' termini from transcripts, and more than 3000 of these were not found among ESTs assembled in UniGene (Build 75). Assessment of the prevalence of polyadenylation signals and comparison with GenBank cDNAs indicated that there was no significant contamination by internally primed cDNAs or genomic fragments but that there was a relatively high incidence (12%) of alternative polyadenylation sites. We evaluated the sensitivity and resolution of expression information in BodyMap by in silico Northern hybridization and selection of tissue-specific gene probes. BodyMap is a unique resource for estimation of the absolute abundance of transcripts and selection of gene probes for efficient hybridization-based gene expression profiling.

3' Untranslated Regions↗

Effect of tranilast oily gel on carrageenin-induced granulation in rats.

Tranilast (TL) oily gels consisting of hydrogenated soybean phospholipid and fatty-acid ester were prepared, and the inhibitory effect of the gels on the growth of granulation tissue were evaluated in a carrageenin-induced rat granulation model. By the application of 0.1 and 0.2% TL oily gel, the weight of granulation tissue was significantly reduced to 64 and 55%, respectively, of control value. Furthermore, these gels reduced their respective hydroxyproline content to 64 and 51% of the control. On the other hand, the inhibitory effect of 10% TL ointments, which are clinically used for the treatment of keloids and hypertrophic scars as hospital preparations, was much lower than that of the oily gels. In addition, the application of 0.1 and 0.2% oily gel led to high concentration (0.1% gel, 168+/-18 microg/g; 0.2% gel, 221+/-16 microg/g) of TL in the dermis as compared with the 10% TL ointments. These results suggest that TL oily gels may be a useful topical formulation for the treatment of keloids and hypertrophic scars.

Administration, Topical↗

Cloning and functional expression of an SGLT-1-like protein from the Xenopus laevis intestine.

A cDNA encoding an Na+-glucose cotransporter type 1 (SGLT-1)-like protein was cloned from the Xenopus laevis intestine by the 5'- and 3'-rapid amplification of cDNA ends method. The deduced amino acid sequence was 673 residues long, with a predicted mass of 74.1 kDa and 52-53% identity to mammalian SGLT-1s. This gene was expressed in the small intestine and kidney, reflecting a tissue distribution similar to that of SGLT-1. The function of the protein was studied using the two-microelectrode voltage-clamp technique after injection of cRNA into Xenopus laevis oocytes. Perfusion with myo-inositol elicited about twofold larger inward currents than perfusion with D-glucose. The order of the substrate specificity was myo-inositol > D-glucose > D-galactose >/= alpha-methyl-D-glucoside. The current induced by myo-inositol increased with membrane hyperpolarization and depended on external myo-inositol and Na+: the apparent Michaelis-Menten constant was 0.25 +/- 0.07 (SD) mM with myo-inositol, whereas the apparent concentration for half-maximal activation was 12.5 +/- 1.0 mM and the Hill coefficient was 1.6 +/- 0.1 with Na+. In conclusion, the cloned protein shares features with both SGLT-1 and the Na+-myo-inositol cotransporter.

Amino Acid Sequence↗

Cholinergic systems in the nucleus of the solitary tract of rats.

The pharmacological and physiological properties of excitatory amino acid and ACh systems in the nucleus of the solitary tract (NTS) were studied in slices of rat brain stem by extracellular and intracellular recordings from neurons activated by solitary tract (ST) stimulation. These neurons were characterized as having several long dendrites with multiple varicosities. Synaptic activation of the medial NTS (mNTS) neurons by ST stimulation was mediated by non-N-methyl-D-aspartate (NMDA) glutamate (Glu) receptors, because the excitation was blocked by 6-cyano-7-nitro-quinoxaline-2,3-dione but not by NMDA, nicotinic, or muscarinic antagonists. Identified mNTS neurons were excited by iontophoresis of both Glu and ACh. The most sensitive region of the cell was on the dendrites approximately 100 micrometer from the cell body for both putative neurotransmitters. Nicotinic and/or muscarinic excitatory ACh responses were detected on the mNTS neurons. Our observations suggest that both types of ACh receptors may contribute to the attenuation of the baroreceptor reflex, but the functional correlation of this receptor profile remains to be determined.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Effect of UV-absorbing agents on photodegradation of tranilast in oily gels.

Tranilast (TL) oily gels containing UV-absorbing agents (UV absorber) were prepared, and the effect of the agents against photodegradation of TL was investigated. When 0.1% TL oily gel without UV absorber was exposed to light, TL was photochemically decomposed to the extent of 74.1% of its initial content at the end of the first hour. Although there were differences in the preventive effect on photodegradation of TL depending on the UV absorbers employed, 2-(2-benzotriazolyl)-p-cresol (BTPC) was the most effective absorber. The addition of UV absorbers to the oily gel did not affect the release of TL from the gel, the skin permeation, or the skin concentration of TL following topical application. UV absorbers added to TL oily gel penetrated into skin; however, their concentration in skin was similar to that following application of commercial sunscreen. These results suggest that the addition of UV absorbers to the oily gel of TL may be useful in preventing photodegradation of TL in the gel.

Animals↗

Endothelin-1 facilitates synaptic transmission in the nucleus tractus solitarii in normotensive rats but not in spontaneously hypertensive rats.

We previously demonstrated that endothelin-1 (ET-1) increases the neuronal activity of neurons in the nucleus tractus solitarii (NTS) and augments the response to glutamate (Glu), using in vitro brainstem slice preparations of normotensive Wistar-Kyoto (WKY) rats. This study was designed to determine whether the effects of ET-1 on neuronal activity and synaptic transmission in the NTS are altered in spontaneously hypertensive rats (SHR). Experiments were performed with WKY rats and age-matched SHR. We recorded the extracellular single unit of neuronal activity of NTS neurons in response to electrical stimulation of the solitary tracts using in vitro brainstem slice preparations. ET-1 or Glu was iontophoretically applied to the recording neurons. ET-1 increased the neuronal activity of NTS neurons in SHR as well as WKY. The magnitude of the increase in the neuronal activity evoked by Glu was augmented by application of ET-1 in WKY rats (6.1 +/- 0.6 to 11.1 +/- 1.7 spikes/s, p < 0.05) but not in SHR (5.6 +/- 0.5 to 5.6 +/- 0.6 spikes/s). These results indicate that ET-1 increases the neuronal activity of the NTS in both SHR and WKY. However, the increase in neuronal activity in response to Glu is augmented by ET-1 in WKY but not in SHR, suggesting that reflex control is impaired in SHR.

Animals↗

Effects of arginine-vasopressin on neuronal interaction from the area postrema to the nucleus tractus solitarii in rat brain slices.

The effects of arginine-vasopressin (AVP) on area postrema (AP) neurons and the neuronal connection between the AP and nucleus tractus solitarii (NTS) were electrophysiologically investigated in rat medulla slices. In the AP, 27.9% of 129 neurons were excited by AVP and 20.5% were inhibited. The excitation was blocked by an V1 receptor antagonist. Synaptic transmission of the AP to the NTS was mainly mediated by non-N-methyl-D-aspartate (NMDA) receptors. Local application of AVP to the AP activated the NTS neurons. This excitation was also blocked by an NMDA antagonist. These results suggest that the excitation originating in the AP is conveyed to the NTS via non-NMDA receptors and then modified by NMDA receptor activation secondly. These processes may be important in the regulation of the arterial baroreceptor reflex.

2-Amino-5-phosphonovalerate↗

Anti-emetic effects of a novel NK-1 receptor antagonist HSP-117 in ferrets.

We have developed a non-peptide compound, HSP-117, antagonist of the tachykinin NK-1 receptor. Binding of 3H-substance P (SP) to the membranes of IM-9 cells was inhibited by the antagonists HSP-117 and CP-99,994, the inhibitory activity of HSP-117 being about 50-fold that of CP-99,994. The SP-induced firing responses of single neuron activity in slices of the nucleus tractus solitarius of ferrets were inhibited by 10 microM HSP-117. Intracerebroventricular injection of HSP-117 significantly inhibited retching and vomiting induced by copper sulphate and morphine and the inhibitory effect of HSP-117 on emesis was greater than that of CP-99,994. These results indicate that (1) HSP-117 is a potent anti-emetic agent, blocking NK-1 receptors in the nucleus tractus solitarius and (2) NK-1 receptors in the nucleus tractus solitarius play an important role in emesis induced by broad-spectrum emetic stimuli.

Animals↗

Inhibition of membrane-type 1 matrix metalloproteinase by hydroxamate inhibitors: an examination of the subsite pocket.

The membrane-type 1 matrix metalloproteinase (MT1-MMP) has been reported to mediate the activation of pro-gelatinase A (proMMP-2), which is associated with tumor proliferation and metastasis. MT1-MMP can also digest extracellular matrix (ECM) such as interstitial collagens, gelatin, and proteoglycan and thus may play an important role in pathophysiological digestion of ECM. We studied the inhibitory effect of various hydroxamate MMP inhibitors, including known inhibitors such as BB-94, BB-2516, GM6001, and Ro31-9790, on a deletion mutant of MT1-MMP lacking the transmembrane domain (DeltaMT1) to further characterize the enzyme and develop a selective inhibitor for MT1-MMP. The evaluation of the inhibitory activities of various hydroxamates reveals general structural profiles affecting selectivities toward MMPs. In particular, a longer side chain at the P1' position is preferable for the binding to MMP-2, -3, and -9 and MT1-MMP. For the P2' position, an alpha-branched alkyl group is critical for the binding toward DeltaMT1, while the introduction of a bulky group at the alpha-position of hydroxamic acid seems to diminish the activity against DeltaMT1. Summation of the data on the sensitivity of DeltaMT1 to various hydroxamate inhibitors indicates that (1) the volume of the S1' subsite of DeltaMT1 is similar to that of MMP-2, -3, and -9, which is bigger than that of MMP-1, and (2) the S1 and S2' subsites are narrower than those in other MMPs. On the basis of these results, the hydroxamates with a P1' phenylpropyl and P2' alpha-branched alkyl group were synthesized and evaluated for inhibitory activity. These inhibitors (1h,i) showed strong activity against DeltaMT1 over MMP-1, but no selectivity between DeltaMT1 and MMP-9. These results are explained using molecular modeling studies conducted on MT1-MMP.

Amino Acid Sequence↗

Ataxia-telangiectasia without immunodeficiency: novel point mutations within and adjacent to the phosphatidylinositol 3-kinase-like domain.

Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterized by progressive ataxia, telangiectasia, sinopulmonary infections, hypersensitivity to ionizing radiation, and combined immunodeficiency. Recently, the AT gene (ATM) was cloned and shown to be mutated in AT patients. In this report, mutation analysis of ATM was performed in a 24-year-old AT patient without immunodeficiency. ATM amplified with reverse transcriptase-polymerase chain reaction (RT-PCR) was screened with a ribonuclease (RNase) cleavage assay and auto-sequenced. This patient, a compound heterozygote, showed two mutations in ATM: one missense mutation leading to a Leu2656Pro substitution and the other to the truncation at codon 3047 (Arg-->ter). The latter mutation is within the phosphatidylinositol 3-kinase (PI 3-kinase)-like domain and the former is outside but close to the domain. The particular phenotype in our patient, no immunodeficiency, suggests incomplete functional loss of ATM protein. The clinical spectrum of AT caused by ATM mutations may be broader than previously thought. Further analysis of patients with similar phenotypes will make the relation between ATM genotype and phenotype clear.

Adult↗

Enhanced release of nitric oxide in response to changes in flow and shear stress in the superior mesenteric arteries of portal hypertensive rats.

Increased nitric oxide (NO) release has been implicated in the pathogenesis of the hyperdynamic circulation in portal hypertension. NOS 3 (eNOS) causes NO release from the endothelium in response to physical stimuli, such as increased blood flow and shear stress. We evaluated the functional activity of the endothelium in the superior mesenteric arterial bed of portal hypertensive rats through direct measurement of NO metabolites (NOx) during changes in flow and shear stress. The in vitro perfusion system (McGregor) was used in sham and portal vein-ligated (PVL) rats. Shear stress was applied gradually to superior mesenteric arterial beds by increasing the perfusion rate. Flow studies were performed serially before and after incubation with either Krebs solution alone or with the NO-inhibitor, NG-monomethyl-L-arginine (L-NMMA). NOx concentrations in the perfusate were measured using chemiluminescence. The slope of NOx release versus flow-induced shear stress was calculated. Before L-NMMA administration, NOx concentrations and release of NO in PVL rats were significantly elevated in comparison with sham rats at flow rates of 32, 40, and 48 mL/min. The slope of NOx production versus shear stress index was significantly higher in PVL than in sham rats. After L-NMMA incubation, the decrease in slope was significantly larger in PVL rats. This study provides direct evidences of an increased NO synthesis by the superior mesenteric arterial vascular endothelium of PVL animals in response to shear stress. The increased NO output in response to shear stress suggests an adaptative mechanism developed by the vascular endothelial cells in response to a chronic increase in flow-mediated shear stress.

Animals↗

Distribution of calretinin immunoreactivity in the mouse dentate gyrus: II. Mossy cells, with special reference to their dorsoventral difference in calretinin immunoreactivity.

In our previous study we revealed the presence of clustered large calretinin-immunoreactive multipolar cells in the ventral hilus of the mouse dentate gyrus and indicated that they might be mossy cells, the principal neurons in the dentate hilus. In the present study we confirmed this identification with several methods and analysed further in detail. In Golgi-impregnated samples mossy cells were easily identified by their locations and characteristic thorny excrescences on their proximal dendrites. Golgi-impregnated mossy cells were observed not only in the ventral hilus but also in the dorsal hilus, where no calretinin-immunoreactive large multipolar cells were encountered. Interestingly, mossy cells exhibited dorsoventral differences in the size and complexity of thorny excrescences; mossy cells at the dorsal and middle levels had larger and more complex thorny excrescences, which covered dendritic shafts for a longer distance, while ventral mossy cells had smaller, simpler and shorter thorny excrescences. Confocal laser scanning light microscopic observations at a high magnification showed that the vast majority of calretinin-immunoreactive large neurons in the ventral hilus displayed the thorny excrescences characteristic to mossy cells. Mossy cells identified with the intracellular injection of Lucifer Yellow were calretinin-immunoreactive. Electron microscopic observations clearly revealed that calretinin-immunoreactive elements showed structural features of mossy cells such as thorny excrescences receiving typical synapses from mossy fibre terminals. At the supragranular zone, a well-known target zone of mossy cell axons, a dense calretinin-immunoreactive band was seen, where numerous calretinin-immunoreactive punctae and fibres were packed. Electron microscopic observations revealed that these calretinin-immunoreactive axon terminals in the supragranular zone made asymmetrical synapses on presumed granule cell dendritic spines. Tracer injection studies and lesion experiments indicated that the supragranular calretinin-immunoreactive axon terminals mainly originated from the large calretinin-immunoreactive multipolar cells in the ipsilateral ventral hilus. Fluorescent double immunostaining for calretinin and glutamate receptor 2/3 (GluR2/3) revealed that all large calretinin-immunoreactive hilar cells in the ventral level were GluR2/3-immunoreactive and almost all intensely GluR2/3-immunoreactive hilar cells in the ventral level were calretinin-immunoreactive. In addition intensely GluR2/3-immunoreactive but calretinin-negative large cells were encountered in the dentate hilus at the dorsal level. On the basis of these observations, we concluded that large calretinin-immunoreactive cells in the ventral hilus of the mouse dentate gyrus were really mossy cells and that mossy cells at the dorsal level were calretinin negative. The present study revealed that mouse mossy cells show the dorsoventral difference in the calretinin immunoreactivity and thus they are chemically heterogeneous.

Animals↗

Endothelin-1 increases the neuronal activity and augments the responses to glutamate in the NTS.

The aims of this study were to determine 1) whether endothelin (ET)-1 affects the neuronal activity of the NTS neurons, 2) whether specific ET receptor antagonists affect the neuronal activity of the NTS neurons, and 3) whether ET-1 or ET receptor antagonists modulate the responses of the nucleus of the solitary tract (NTS) neurons to L-glutamate (Glu). The single-unit discharge was extracellularly recorded with a fine electrode from medulla brain slice preparations of rats. ET-1 and Glu were iontophoretically applied to the recorded neuron. Both ET-1 and Glu increased the neuronal activity. The ETA receptor antagonist BQ-123 attenuated the basal neuronal activity. ET-1 augmented the magnitude of the increases in the neuronal activity evoked by Glu, and these responses were antagonized by BQ-123. These studies suggest the following conclusions: 1) ET-1 increases the neuronal activity of the NTS neurons via ETA receptors, 2) endogenous ET plays a controlling role of the neuronal activity of NTS neurons, and 3) ET-1 augments the responses evoked by Glu, believed to be the neurotransmitter from the solitary tract, via ETA receptors. These results suggest that ET-1 facilitates synaptic transmission in the NTS.

Animals↗

In vitro release of tranilast from oily gels and penetration of the drug into Yucatan micropig skin.

For the transdermal delivery of tranilast (TL), a drug used for the treatment of skin diseases such as keloids and hypertrophic scars, its oily gels were prepared; its in vitro release and penetration into Yucatan micropig skin were evaluated. In the gels that consisted of hydrogenated soybean phospholipids (HSL) and octyl isononanoate (IOIN), a fatty-acid ester, the release of TL from the gels was proportional to the drug content, and the extent of TL released up to 6 h from them was approximately 70% of the amount of applied TL. On the other hand, with the gels consisting of HSL and isocetyl isostearate (ICIS), the release of TL from the gels was about half of that from IOIN gels, even at the same drug concentration. When oily gels were used, the TL skin concentration was rapidly increased compared with the level obtained with suspensions. With 0.1% IOIN gel, a high concentration of TL (ca. 160 microg/g) in the dermis was obtained and continued until at least 48 h. These results suggest that oily gels may be useful for the topical application of TL.

Animals↗

[Effects of arginine-vasopressin on neuronal interaction from the area postrema to the nucleus tractus solitarii in rat brain slices].

The effects of vasopressin (AVP) on area postrema (AP) neurons and the neuronal connection between the AP and nucleus tractus solitarii (NTS) were investigated electrophysiologically in slices preparation of the medulla oblongata of rats. In the AP, 27.9% of 129 neurons were excited by AVP and 20.5% were inhibited. The excitation was blocked by a V1 receptor antagonist. Synaptic transmission of the AP to the NTS was mainly mediated by non-NMDA receptors. Local application of AVP to the AP activated the NTS neurons. This activation was blocked by an NMDA antagonist. These results suggest that the excitation originating in the AP is conveyed to the NTS via non-NMDA receptors and modified by NMDA receptor activation secondly. These processes may be important in regulation of the arterial baroreceptor reflex.

Animals↗

Eighteen novel human genes regionally mapped on chromosome 11.

Expression sequence tags (EST) obtained by sequencing a randomly primed cDNA library and gene signatures (GS) obtained by sequencing a 3'-directed cDNA library can identify genes that are active in the source cells. Eight ESTs and ten GSs which represent novel human genes, except for one GS, and which have been assigned to human chromosome 11 were used to select cosmids from a chromosome 11-specific cosmid library. These cosmids were regionally mapped using the fluorescence in situ hybridization technique.

Animals↗