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T Nambu

Publications and source records attributed to T Nambu.

At least 19 recordsLinked to original sources
PubMed2001

Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity.

Orexins (hypocretins) are a pair of neuropeptides implicated in energy homeostasis and arousal. Recent reports suggest that loss of orexin-containing neurons occurs in human patients with narcolepsy. We generated transgenic mice in which orexin-containing neurons are ablated by orexinergic-specific expression of a truncated Machado-Joseph disease gene product (ataxin-3) with an expanded polyglutamine stretch. These mice showed a phenotype strikingly similar to human narcolepsy, including behavioral arrests, premature entry into rapid eye movement (REM) sleep, poorly consolidated sleep patterns, and a late-onset obesity, despite eating less than nontransgenic littermates. These results provide evidence that orexin-containing neurons play important roles in regulating vigilance states and energy homeostasis. Orexin/ataxin-3 mice provide a valuable model for studying the pathophysiology and treatment of narcolepsy.

Animals↗
PubMed2001

Behaviour of pathogenic E. coli and Salmonella enteritidis in small domestic sewage treatment apparatus ("Johkasou").

"Johkasou" is a small sewage treatment apparatus commonly used in Japan which can effectively treat domestic wastewater in places where a public sewage system is difficult to supply. The behaviour of enterohaemorrhagic E. coli O157 and Salmonella enteritidis in a "Johkasou" was studied. Their reduction rates depended significantly on the water temperature in the "Johkasou" with minimal decrease in numbers at 10 degrees C within 48 h. The reduction rates increased at 20 degrees C and 30 degrees C where 4 log reduction could be expected. The reduction rates were influenced by the BOD of the solutions that contained the pathogens with the lower the BOD the higher the reduction rate. The reduction rates were about the same between both pathogens. The result showed that it was necessary to disinfect the effluent as some pathogens can pass through the apparatus when some users of the apparatus excrete pathogens.

Escherichia coli↗
PubMed2000

Orexin-induced hyperlocomotion and stereotypy are mediated by the dopaminergic system.

We demonstrated involvement of the ventral tegmental area (VTA) dopaminergic system in orexin-induced hyperlocomotion and stereotypy in rats. In double-label immunohistochemical study of rat brain, we found that tyrosine hydroxylase (TH)-immunoreactive cells in the VTA received innervation from orexin immunoreactive-fibers. Orexin-A induced an increase in [Ca(2+)](i) in isolated A10 dopamine neurons in a dose-dependent manner. In behavioral studies, we found that orexin-A induced hyperlocomotion, stereotypy and grooming behavior when administered centrally in rats, and these effects were abolished by dopamine D(2) (haloperidol and sulpiride) or D(1) (SCH23390) antagonists. These results suggest that the orexin-induced hyperlocomotion, stereotypy and grooming behavior are mediated by the dopaminergic system and this pathway might be involved in orexin-induced emotional responses.

Animals↗
PubMed2000

Orexin-induced food intake involves neuropeptide Y pathway.

Orexins (orexin-A and -B) are recently identified neuropeptides, which are thought to be implicated in the regulation of feeding behavior. We used a NPY-Y1 receptor specific antagonist, BIBO3304, to examine whether NPY is involved in orexin-induced feeding behavior. Intracerebroventricular administration of orexin-A (10 nmol) induced food intake in rats (food intake for 3 h; vehicle 0.3+/-0.2 g vs. orexin-A 10 nmol, 4.0+/-0.5 g, n=4). Orexin-induced feeding behavior was partially inhibited by prior administration of BIBO3304 (3 h food intake: orexin-A 10 nmol, 4.0+/-0.5 g vs. BIBO3304 (60 microgram) + orexin-A 10 nmol, 2.2+/-0.2 g, n=4). A low dose of BIBO3304 (30 microgram) did not show a significant inhibitory effect. BIBO3457, an inactive enantiomer, used as a negative control, did not show any inhibitory effect on orexin-A-induced feeding behavior. Fos expression was observed in NPY-containing neurons in the arcuate nucleus 1 h after orexin-A (10 nmol) was administered intracerebroventricularly (control 0.3+/-0.08%, orexin-A 10.2+/-0.8%, n=5 rats/group). These observations suggest that NPY is involved in orexin-induced feeding behavior. However, BIBO3304 did not completely abolish the effect of orexin-A. These results suggest that orexin-A elicits feeding behavior partially via the NPY pathway. The NPY system could be the one of downstream pathways by which orexin-A induces feeding behavior. Another pathway may also be involved in orexin-A-induced feeding behavior, because BIBO3304 did not completely abolish orexin-A-induced feeding behavior.

Animals↗
PubMed2000

Elucidation of accuracy in calibration of MR signal intensity based on transmission amplitude method.

To calibrate magnetic resonance (MR) signal intensity that depends on radio frequency (RF) coil loading, the transmission amplitude (TRA) for the excitation in the transmit-receive RF coil has been used as a good index in the so-called TRA method. As this TRA method needs neither an internal reference nor an additional external reference for the calibration, its accuracy is free from reference measurements. This study elucidated the calibration accuracy of MR signal intensities based on the TRA method. A cylindrical gel phantom was used for accuracy measurements with a 1.5-T MRI unit with conventional T1 imaging as a simple pulse sequence for various loading conditions. The brain parenchyma of eight healthy volunteers also showed calibrated MR signal deviations. The error of the phantom calibration measurements was 2.18% (S.D.%). The background noise intensity of images was theoretically derived to correlate with the impedance mismatching of the RF coil, which is inevitable for fixed tuning, even for automatic tuning that is not always exact. Taking into account this noise intensity, the calibration method was modified to reduce its error to 1.50%. The standard deviations of the calibrated values in the thalamus and frontal white matter were 2.9 and 3.8%, respectively. We suggest that the modified TRA method is a practical and reliable technique to obtain clinical numeric evidence.

Brain↗
PubMed2000

Wavelet compression on detection of brain lesions with magnetic resonance imaging.

The purpose of this report is to assess clinically acceptable compression ratios on the detection of brain lesions at magnetic resonance imaging (MRI). Four consecutive T2-weighted and the corresponding T1-weighted images obtained in 20 patients were studied for 109 anatomic sites including 50 with lesions and 59 without lesions. The images were obtained on a 1.5-T MR unit with a pixel size of 0.9 to 1.2 x 0.47 mm and a section thickness of 5 mm. The image data were compressed by wavelet-based algorithm at ratios of 20:1, 40:1, and 60:1. Three radiologists reviewed these images on an interactive workstation and rated the presence or absence of a lesion with a 50 point scale for each anatomic site. The authors also evaluated the influence of pixel size on the quality of image compression. At receiver operating characteristic (ROC) analysis, no statistically significant difference was detected at a compression ratio of 20:1. A significant difference was observed with 40:1 compressed images for one reader (P = .023), and with 60:1 for all readers (P = .001 to .012). A root mean squared error (RMSE) was higher in 0.94- x 0.94-mm pixel size images than in 0.94- x 0.47-mm pixel size images at any compression ratio, indicating compression tolerance is lower for the larger pixel size images. The RMSE, subjective image quality, and error images of 10:1 compressed 0.94- x 0.94-mm pixel size images were comparable with those of 20:1 compressed 0.94- x 0.47-mm pixel size images. Wavelet compression can be acceptable clinically at ratios as high as 20:1 for brain MR images when a pixel size at image acquisition is around 1.0 x 0.5 mm, and as high as 10:1 for those with a pixel size around 1.0 x 1.0 mm.

Algorithms↗
PubMed2000

Natural progression of osteochondritis dissecans of the humeral capitellum: initial observations.

PURPOSE: To determine the earliest findings, subsequent changes, and natural course of osteochondritis dissecans of the humeral capitellum. MATERIALS AND METHODS: Among 95 patients with osteochondritis dissecans of the humeral capitellum, 16 (mean age, 12.5 years) were selected for this retrospective study because they seemed to have early osteochondritis dissecans and had been followed up without any surgical treatment for 6 months or more (mean, 3.5 years). RESULTS: The initial imaging appearances of the 16 patients' lesions were divided into two types: localized subchondral bone flattening without fragments in seven, and nondisplaced fragments in nine. Patients with lesion flattening had younger ages and significantly shorter durations of symptoms, and most had open growth plates. In five of the seven with flattening, new bone formed over the flattened bone, and the fragments united after arm motion reduction. In contrast, patients with nondisplaced fragments at clinical presentation had longer durations of symptoms with continued arm motion, and their nondisplaced fragments failed to unite. CONCLUSION: The earliest feature of osteochondritis dissecans is subchondral bone flattening, over which new bone subsequently forms. The new bone then can unite with the underlying bone. However, if subjected to repetitive forces over a given time, unstable fragments develop. These fragments, even if not yet displaced, are unable to unite.

Adolescent↗
PubMed2000

Sonographic assessment of osteochondritis dissecans of the humeral capitellum.

OBJECTIVE: The purpose of this study was to determine the efficacy of sonography for revealing osteochondritis dissecans of the humeral capitellum. SUBJECTS AND METHODS: Twenty-seven patients with capitellar osteochondritis dissecans (27 males; range, 11-20 years; mean age, 14 years) underwent radiography and sonography performed with a 7.5-MHz mechanical sector probe. Lesions were assessed as stable or unstable. The sonographic assessment was compared with radiographic assessment in 27 patients, MR assessment obtained in 10, and surgical findings in 15. RESULTS: Sonographic assessment agreed with radiographic assessment in 23 of the 27 patients, MR assessment in nine of the 10, and surgical findings in 14 of the 15. Sonography revealed that two lesions, which had been underestimated on radiography, were unstable. CONCLUSION: Sonography facilitates the assessment of capitellar lesions so that treatment can be optimized.

Adolescent↗
PubMed1999

Orexins/hypocretins regulate drinking behaviour.

Orexin/hypocretins are recently identified neuropeptides which regulate feeding behaviour. We found orexins increased water intake when administrated intracerebroventricularly to rats. The effect of orexin-A was more potent as compared with orexin-B, suggesting the possible involvement of OX(1) receptor. The efficacy of orexin-A was almost comparable with that of angiotensin II, and the effect lasted more than 3 h. Prepro-orexin mRNA level was up-regulated when rats were deprived of water. Orexin-immunoreactive varicose axons were observed in the subfornical organ and area postrema, regions implicated in drinking behaviour. These observations suggest a physiological role for orexin as mediators that regulate drinking behaviour.

Angiotensin II↗
PubMed1999

Distribution of orexin neurons in the adult rat brain.

Orexin (ORX)-A and -B are recently identified neuropeptides, which are specifically localized in neurons within and around the lateral hypothalamic area (LHA) and dorsomedial hypothalamic nucleus (DMH), the regions classically implicated in feeding behavior. Here, we report a further study of the distribution of ORX-containing neurons in the adult rat brain to provide a general overview of the ORX neuronal system. Immunohistochemical study using anti-ORX antiserum showed ORX-immunoreactive (ir) neurons specifically localized within the hypothalamus, including the perifornical nucleus, LHA, DMH, and posterior hypothalamic area. ORX-ir axons and their varicose terminals showed a widespread distribution throughout the adult rat brain. ORX-ir nerve terminals were observed throughout the hypothalamus, including the arcuate nucleus and paraventricular hypothalamic nucleus, regions implicated in the regulation of feeding behavior. We also observed strong staining of ORX-ir varicose terminals in areas outside the hypothalamus, including the cerebral cortex, medial groups of the thalamus, circumventricular organs (subfornical organ and area postrema), limbic system (hippocampus, amygdala, and indusium griseum), and brain stem (locus coeruleus and raphe nuclei). These results indicate that the ORX system provides a link between the hypothalamus and other brain regions, and that ORX-containing LHA and DMH neurons play important roles in integrating the complex physiology underlying feeding behavior.

Age Factors↗
PubMed1999

Neurons containing orexin in the lateral hypothalamic area of the adult rat brain are activated by insulin-induced acute hypoglycemia.

Orexin-A and -B (also known as hypocretin-1 and -2) are neuropeptides which stimulate food intake when administered intracerebroventricularly. Orexins are specifically localized in neurons within and around the lateral hypothalamic area (LHA). Previous electrophysiological studies have demonstrated that some neurons in the LHA are activated by hypoglycemia, and are therefore termed 'glucose-sensitive neurons'. In the present study, we examined whether orexin-containing neurons are activated in the hypoglycemic states, using Fos-like immunoreactivity (FLI) as a marker of neuronal activation. We observed that FLI was induced in the LHA by acute insulin treatment. Double staining with anti-Fos and anti-orexin antibodies revealed that up to 33% of the orexin-containing neurons in the LHA also expressed FLI under the hypoglycemic condition. These results suggest that some populations of neurons which contain orexins are activated under hypoglycemic conditions.

Animals↗
PubMed1999

Structure, tissue distribution, and pharmacological characterization of Xenopus orexins.

We isolated the Xenopus gene encoding prepro-orexin to predict the structures of orexins in submammalian chordates. Putative mature Xenopus orexin-A and -B are highly similar to each mammalian counterpart. Especially, the C-terminal 10 residues were highly conserved among these species and isopeptides. Immunohistochemical examination of Xenopus brain revealed that orexin-containing neurons were highly specifically localized in the ventral hypothalamic nucleus. A rich network of immunoreactive fibers was found in various regions of the Xenopus brain. The distribution was similar to that of mammalian orexins. Xenopus orexin-A and -B specifically bind and activate human orexin receptors expressed in Chinese hamster ovary cells. Of interest, Xenopus orexin-B had several-fold higher affinity to human OX2R compared with human orexins. These results suggest that Xenopus orexin-B might be a useful pharmacological tool as an OX2R selective high-affinity agonist.

Amino Acid Sequence↗
PubMed1999

Peptidoglycan-hydrolyzing activity of the FlgJ protein, essential for flagellar rod formation in Salmonella typhimurium.

Because the rod structure of the flagellar basal body crosses the inner membrane, the periplasmic space, and the outer membrane, its formation must involve hydrolysis of the peptidoglycan layer. So far, more than 10 genes have been shown to be required for rod formation in Salmonella typhimurium. Some of them encode the component proteins of the rod structure, and most of the remaining genes are believed to encode proteins involved in the export process of the component proteins. Although FlgJ has also been known to be involved in rod formation, its exact role has not been understood. Recently, it was suggested that the C-terminal half of the FlgJ protein has homology to the active center of some muramidase enzymes from gram-positive bacteria. In this study, we showed that the purified FlgJ protein from S. typhimurium has a peptidoglycan-hydrolyzing activity and that this activity is localized in its C-terminal half. Through oligonucleotide-directed mutagenesis, we constructed flgJ mutants with amino acid substitutions in the putative active center of the muramidase. The resulting mutants produced FlgJ proteins with reduced enzymatic activity and showed poor motility. These results indicate that the muramidase activity of FlgJ is essential for flagellar formation. Immunoblotting analysis with the fractionated cell extracts revealed that FlgJ is exported to the periplasmic space, where the peptidoglycan layer is localized. On the basis of these results, we conclude that FlgJ is the flagellum-specific muramidase which hydrolyzes the peptidoglycan layer to assemble the rod structure in the periplasmic space.

Amino Acid Substitution↗
PubMed1993

[Evaluation of EC-IC bypass flow by MR angiography using the presaturation technique].

MR angiography studies using the presaturation technique were performed in 7 patients who had received extra-intracranial (EC-IC) bypass surgery. With presaturation on the bypass vessels, disappearance of intracranial vascular signals suggests bypass effect. In our studies, good bypass effect was shown in 3 cases and poor effect in 2 cases, which correlates well to concurrent angiography. In two cases, bypass effect was shown only in a few cortical branches of MCA, but angiography confirmed recanalization of occluded internal carotid artery in one case, and growth of large network of transdural anastomoses in the other.

Adult↗