Synthetic study towards azadirachtin: an efficient and stereoselective construction of the AB rings with full functionality.
Explore the source record for details and available documents.
Azadirachta↗
Biomedical subjects
Kenji Mori
Publications and source records attributed to Kenji Mori.
Short-latency somatosensory evoked potentials in infantile autism: evidence of hyperactivity in the right primary somatosensory area.
Children with infantile autism sometimes show hyperesthesia or hypoesthesia to touch, pain, and/or temperature. To clarify the pathophysiology, we examined short-latency somatosensory evoked potentials (S-SEPs), elicited by median nerve stimulation, in 24 children with infantile autism (17 males, seven females; age range 2y 2mo-9y; mean age 4y 2mo [SD 1y 7mo]). We also evaluated relationships between S-SEP findings and clinical manifestations. Of the 24 children, 10 showed abnormal S-SEPs as follows: prolonged peak latency of N20 (n=2), extended interpeak latency of P13/14-N20 (n=7), appearance of a giant SEP (n=1), and a more than twofold right hemispheric peak-to-peak amplitude predominance of N20-P25 (n=5). In addition, a peak-to-peak amplitude of N20-P25 elicited by left median nerve stimuli was significantly higher than that obtained with right median nerve stimuli, which indicated right hemispheric hyperactivity relative to the left (p=0.008). Infantile autism is frequently associated with somatosensory abnormalities and right hemispheric hyperactivity relative to the left, especially in the primary somatosensory area. This is believed to contribute to the pathophysiology of infantile autism, especially the idiopathic form.
Autistic Disorder↗
A case of Kabuki syndrome presenting West syndrome.
A 6-month-old girl visited our hospital because of mental retardation, regression, and tonic spasms in cluster. We diagnosed her as West syndrome because of hypsarrhythmia on electroencephalogram (EEG) and tonic spasms in cluster. We also diagnosed her as Kabuki syndrome because of multiple malformations, especially a characteristic peculiar face (resembling a Kabuki actor). She was first administered clonazepam, but this was not effective. Later, she was administered vitamin B6, valproic acid, and zonisamide. Zonisamide was effective, and her tonic spasms were suppressed. Her EEG at 9 months of age showed the disappearance of hypsarrhythmia and sporadic spike and wave complexes on P3, P4, O1, and O2. At 2 years of age, she still showed mental retardation, despite the good control of West syndrome. To the best of our knowledge, Kabuki syndrome presenting West syndrome has been reported in only one previous case. We must pay attention to the occurrence of West syndrome in Kabuki syndrome.
Abnormalities, Multiple↗
Patients with West syndrome whose ictal SPECT showed focal cortical hyperperfusion.
To clarify the mechanism of clustered spasms in West syndrome (WS), we examined ictal SPECT and EEG, as well as those during the interictal period, in three patients with symptomatic WS who had apparent focal cerebral lesions. For ictal SPECT and EEG, we monitored the patients with EEG, and as soon as we noticed the occurrence of clustered spasms clinically and electroencephalographically, [(99m)Tc]ECD was injected intravenously and flushed thoroughly with saline. In these three patients, regional cerebral blood flow (rCBF) increased during ictus and decreased during the interictal period in the area that coincided with the focal cerebral lesion recognized by CT/MRI. The ictal hyperperfusion of bilateral basal ganglia was also detected in two of the three patients. The ictal EEG showed a diffuse slow wave complex corresponding to a clinical spasm. The sharp waves that preceded the diffuse slow wave complex and the spasm appeared in the same area in which rCBF increased during ictus. None of the patients showed partial seizure before or after clustered spasms clinically or electroencephalographically during the ictal SPECT study. Secondary generalization from a cerebral focus may explain the mechanism of spasms in these patients with WS: focal cortical discharge may primarily generate clustered spasms and trigger the brainstem and basal ganglia structures to produce spasms.
Cerebral Cortex↗
Structural and functional analogs of the novel mammalian neuropeptide, neuromedin S (NmS), in the dermal venoms of Eurasian bombinid toads.
We report the isolation and structural characterization of two neuromedin S (NmS) analogs, (NmS-17 and NmS-33), from the dermal venoms of Eurasian bombinid toads. NmS is a novel neuromedin U (NmU)-related peptide with potent anorexigenic and circadian rhythm-modulating properties recently discovered in mammals. Cloning of NmS precursor-encoding cDNAs from skin venom-derived libraries revealed the presence of a high degree of transcript splice variation comparable to that found previously for NmU in both amphibian skin and mammalian brain. Synthetic replicates of both amphibian NmS peptides evoked robust and dose-dependent transient increases in intracellular calcium ion concentrations in CHO cells that had been stably transfected with either FM-3/GPR66 or FM-4/TGR-1 human NmU receptors. The potency and efficacy of these amphibian skin peptides at such receptors were comparable to those observed with human NmS and rat NmS. These data show that NmS and NmU genes had already diverged at the level of the Amphibia and that differential splicing of their transcribed mRNAs has been highly conserved throughout tetrapod vertebrate evolution indicative of fundamental biological function. NmS is additionally a novel neuropeptide homolog that can be added to the biologically active peptide arsenal of amphibian venom/defensive skin secretions.
Amino Acid Sequence↗
Favorable response of ADHD with giant SEP to extended-release valproate.
We treated three boys with attention deficit/hyperactivity disorder (ADHD) associated with giant somatosensory evoked potentials (SEP). All responded well to extended-release valproate (EVA), a gamma-aminobutyric acid (GABA) enhancer. Improvement particularly involved hyperactivity and impulsivity. When methylphenidate previously was administered to two patients, symptoms worsened. EVA therefore may be preferable for ADHD with giant SEP.
Adolescent↗
A case of idiopathic portal hypertension associated with rheumatoid arthritis.
A 53-year-old woman who had been diagnosed with rheumatoid arthritis was found to have thrombocytopenia, splenomegaly, and gastric varices. She was diagnosed as having idiopathic portal hypertension on the basis of liver biopsy and angiography. Treatment with prednisolone was not sufficiently effective for thrombocytopenia. After transabdominal devascularization with splenectomy, thrombocytopenia subsided and gastric varices disappeared. In this case, the autoimmune mechanism as well as hypersplenism was suspected of being involved in the mechanism of thrombocytopenia.
Arthritis, Rheumatoid↗
A remarkable large hamartoma around the knee in a patient with tuberous sclerosis.
Explore the source record for details and available documents.
Adult↗
Pheromonal activity of compounds identified from male Phyllotreta cruciferae: field tests of racemic mixtures, pure enantiomers, and combinations with allyl isothiocyanate.
Four himachalene sesquiterpenes and (+)-gamma-cadinene, previously identified as possible pheromone components from males of a North American population of Phyllotreta cruciferae Goeze (Coleoptera, Chrysomelidae), were tested for attractiveness in field trapping experiments in Hungary. A mixture of the four synthetic racemic himachalene derivatives and (+)-gamma-cadinene from a botanical source was slightly attractive to beetles, but much more attractive when blended with the known host-plant-derived attractant allyl isothiocyanate. This result was consistent with a previous study in North America. In tests with optically pure synthetic compounds, a blend of the same himachalene enantiomers found from male beetles was equivalent to the corresponding blend of racemic compounds, whereas a blend of the opposite enantiomers was not active. Through subtraction tests, it was found that the single compound, (6R,7S)-2,2,6,10-tetramethylbicyclo[5.4.0.]undeca-9,11-diene [compound (+)-A in this study], was as active as the whole mixture, suggesting that this compound is the key pheromone component of the European population of P. cruciferae. During field trials, several congeneric species, including P. vittula, P. nemorum, P. nodicornis, and P. ochripes, also were caught, suggesting that the same compound(s) may be relatively widespread as pheromone components in this genus.
Animals↗
Administration of secretin for autism alters dopamine metabolism in the central nervous system.
We evaluated the clinical effects of intravenously administered secretin in 12 children with autism (age range: 4-6 years, median age: 9 years, boy:girl=8:4). In addition, we investigated the association between improvement in symptoms and changes in the cerebrospinal fluid (CSF) homovanillic acid (HVA),5-hydroxyindole-3-acetic acid (5-HIAA), and 6R-5,6,7,8-tetrahydro-L-biopterin (BH(4)) levels after administration. After administration of secretin, the Autism Diagnostic Interview-Revised (ADI-R) score improved in 7 of the 12 children. However, the score deteriorated in 2 of the 12 children (in the item of 'restricted and repetitive, stereotyped interests and behaviors'). The HVA and BH(4) levels in CSF were increased in all children with improvement in the ADI-R score. In contrast, no patient without the elevation of the BH(4) level showed improvement in the score. These findings suggest that secretin activated metabolic turnover of dopamine in the central nervous system via BH(4), improving symptoms.
Autistic Disorder↗
Effect of neuromedin S on feeding regulation in the Japanese quail.
Neuromedin S (NMS) was recently isolated from the brains of humans, mice and rats as an endogenous ligand for the orphan G protein-coupled receptors FM-3 and FM-4, which have been identified as neuromedin U (NMU) receptors 1 and 2, respectively. To investigate the role of NMS in avian species, we elucidated the effect of intracerebroventricular (i.c.v.) administration of rat NMS on food intake, body weight, body temperature and gross locomotor activity in adult Japanese quails. NMS significantly decreased food intake (and consequently body weight) in a time-dependent manner during 12-h light period, but increased both body temperature and gross locomotor activity. On the other hand, i.c.v. injection of rat NMU showed the reverse effects of NMS in Japanese quail. These results suggest that NMS may play an important role in regulating food intake and sympathetic nerve activity in the Japanese quail.
Animals↗
Effect of electroporation on the electroosmosis across hairless mouse skin in vitro.
The effect of electroporation on the iontophoresis-produced electroosmosis across the skin was evaluated by measuring the permeability of hairless mouse skin, to mannitol, a non-electrolyte, in vitro. Immediately after electroporation by squared pulses (10 times/s) at 100, 150 or 200 V for 1 ms, anodal iontophoretic permeations were determined at 0.4 mA/cm2 for 4 h. The observed iontophoretic permeability of mannitol was higher with electroporation pretreatment than without pretreatment. The enhanced flux of mannitol induced by electroporation, however, was due to increased passive diffusion. The contribution of convective or osmotic flow caused by anodal iontophoresis on skin permeation of mannitol was decreased by the pretreatment. In addition, osmotic flow was decreased with an increase in the applied voltage for electroporation. In contrast, mannitol flux during cathodal iontophoresis at 0.4 mA/cm2 after 150 or 200 V electroporation was higher than without electroporation as well as anodal iontophoresis, but cathodal iontophoretic flux after electroporation was lower than without iontophoresis. The neutral high-molecular compound dextran rhodamine B was also used as a second model. Anodal iontophoresis alone did not increase skin permeability of the compound. However, electroporation pretreatment before anodal iontophoresis enhanced the skin permeation of dextran rhodamine B, which was due to increased osmotic flow induced by this combination. These results suggest that electroporation decreases the electroosmosis produced by iontophoresis, and that electroporation increases skin permeability to neutral low and high model compounds (mannitol and dextran rhodamine B) probably due to an enlarged permeation pathway. Thus, electroporation affects osmotic flow from the anode to cathode during iontophoresis. Therefore, one has to pay attention to the change in electroosmosis produced by iontophoresis for the combined use of electroporation and iontophoresis to attain a high skin-penetration enhancing effect.
Administration, Topical↗
Neuromedin s is a novel anorexigenic hormone.
A novel 36-amino acid neuropeptide, neuromedin S (NMS), has recently been identified in rat brain and has been shown to be an endogenous ligand for two orphan G protein-coupled receptors, FM-3/GPR66 and FM-4/TGR-1. These receptors have been identified as neuromedin U (NMU) receptor type 1 and type 2, respectively. In this study, the physiological role of the novel peptide, NMS, on feeding regulation was investigated. Intracerebroventricular (icv) injection of NMS decreased 12-h food intake during the dark period in rats. This anorexigenic effect was more potent and persistent than that observed with the same dose of NMU. Neuropeptide Y, ghrelin, and agouti-related protein-induced food intake was counteracted by coadministration of NMS. Icv administration of NMS increased proopiomelanocortin mRNA expression in the arcuate nucleus (Arc) and CRH mRNA in the paraventricular nucleus (PVN). Pretreatment with SHU9119 (antagonist for alpha-MSH) and alpha-helical corticotropin-releasing factor-(9-41) (antagonist for CRH) attenuated NMS-induced suppression of 24-h food intake. After icv injection of NMS, Fos-immunoreactive cells were detected in both the PVN and Arc. When neuronal multiple unit activity was recorded in the PVN before and after icv injection of NMS, a significant increase in firing rate was observed 5 min after administration, and this increase continued for 100 min. These results suggest that the novel peptide, NMS, may be a potent anorexigenic hormone in the hypothalamus, and that expression of proopiomelanocortin mRNA in the Arc and CRH mRNA in the PVN may be involved in NMS action on feeding.
Animals↗
Calcineurin-nuclear factor of activated T cells pathway-dependent cardiac remodeling in mice deficient in guanylyl cyclase A, a receptor for atrial and brain natriuretic peptides.
BACKGROUND: Although disruption of guanylyl cyclase (GC) A, a natriuretic peptide receptor, induces cardiac hypertrophy and fibrosis, the molecular mechanism underlying these effects are not well understood. In this study, we examined the role of calcineurin, a calcium-dependent phosphatase, in cardiac remodeling in GCA-knockout (GCA-KO) mice. METHODS AND RESULTS: At 14 weeks of age, calcineurin activity, nuclear translocation of nuclear factor of activated T cells c3 (NFATc3), and modulatory calcineurin-interacting protein 1 (MCIP1) gene expressions were increased in the hearts of GCA-KO mice compared with wild-type (WT) mice. Blockade of calcineurin activation by FK506 (6 mg/kg body weight administered subcutaneously once a day from 10 to 14 weeks of age) significantly decreased the heart-to-body weight ratio, cardiomyocyte size, and collagen volume fraction in GCA-KO mice, whereas FK506 did not affect these parameters in WT mice. Overexpression of atrial and brain natriuretic peptides, collagen, and fibronectin mRNAs in GCA-KO mice was also attenuated by FK506. Electrophoretic mobility shift assays demonstrated that GATA4 DNA-binding activity was increased in GCA-KO mice, and this increase was inhibited by calcineurin blockade. In neonatal cultured cardiac myocytes, inhibition of GCA by HS142-1 (100 microg/mL) increased basal and phenylephrine (10(-6) mol/L)-stimulated calcineurin activity, nuclear translocation of NFATc3, and MCIP1 mRNA expression. In contrast, activation of GCA by atrial natriuretic peptide (10(-6) mol/L) inhibited phenylephrine (10(-6) mol/L)-stimulated nuclear translocation of NFATc3. CONCLUSIONS: These results suggest that activation of cardiac GCA by locally secreted natriuretic peptides protects the heart from excessive cardiac remodeling by inhibiting the calcineurin-NFAT pathway.
Animals↗
C-type natriuretic peptide, a novel antifibrotic and antihypertrophic agent, prevents cardiac remodeling after myocardial infarction.
OBJECTIVES: We assessed the hypothesis that in vivo administration of C-type natriuretic peptide (CNP) might attenuate cardiac remodeling after myocardial infarction (MI) through its antifibrotic and antihypertrophic action. BACKGROUND: Recently, we have shown that CNP has more potent antifibrotic and antihypertrophic effects than atrial natriuretic peptide (ANP) in cultured cardiac fibroblasts and cardiomyocytes. METHODS: Experimental MI was induced by coronary ligation in male Sprague-Dawley rats; CNP at 0.1 mug/kg/min (n = 34) or vehicle (n = 35) was intravenously infused by osmotic mini-pump starting four days after MI. Sham-operated rats (n = 34) served as controls. After two weeks of infusion, the effects of CNP on cardiac remodeling were evaluated by echocardiograpic, hemodynamic, histopathologic, and gene analysis. RESULTS: C-type natriuretic peptide markedly attenuated the left ventricular (LV) enlargement caused by MI (LV end-diastolic dimension, sham: 6.7 +/- 0.1 mm; MI+vehicle; 8.3 +/- 0.1 mm; MI+CNP: 7.7 +/- 0.1 mm, p < 0.01) without affecting arterial pressure. Moreover, there was a substantial decrease in LV end-diastolic pressure, and increases in dP/dt(max), dP/dt(min), and cardiac output in CNP-treated MI rats compared with vehicle-treated MI rats. Importantly, CNP infusion markedly attenuated an increase in morphometrical collagen volume fraction in the noninfarct region (sham: 3.1 +/- 0.2%; MI+vehicle: 5.7 +/- 0.5%; MI+CNP: 3.9 +/- 0.3%, p < 0.01). In addition, CNP significantly reduced an increase in cross-sectional area of the cardiomyocytes. These effects of CNP were accompanied by suppression of MI-induced increases in collagen I, collagen III, ANP, and beta-myosin heavy chain messenger ribonucleic acid levels in the noninfarct region. CONCLUSIONS: These data suggest that CNP may be useful as a novel antiremodeling agent.
Animals↗
Ingested medium-chain fatty acids are directly utilized for the acyl modification of ghrelin.
Ghrelin, an acylated brain and gut peptide, is primarily produced by endocrine cells of the gastric mucosa for secretion into the circulation. The major active form of ghrelin is a 28-amino-acid peptide containing an n-octanoyl modification at serine that is essential for activity. Studies have identified multiple physiological functions for ghrelin, including GH release, appetite stimulation, and metabolic fuel preference. Until now, there has not been any report detailing the mechanism of ghrelin acyl modification. Here we report that ingestion of either medium-chain fatty acids (MCFAs) or medium-chain triacylglycerols (MCTs) increased the stomach concentrations of acylated ghrelin without changing the total (acyl- and des-acyl-) ghrelin amounts. After ingestion of either MCFAs or MCTs, the carbon chain lengths of the acyl groups attached to nascent ghrelin molecules corresponded to that of the ingested MCFAs or MCTs. Ghrelin peptides modified with n-butyryl or n-palmitoyl groups, however, could not be detected after ingestion of the corresponding short-chain or long-chain fatty acids, respectively. Moreover, n-heptanoyl ghrelin, an unnatural form of ghrelin, could be detected in the stomach of mice after ingestion of either n-heptanoic acid or glyceryl triheptanoate. These findings indicate that ingested medium-chain fatty acids are directly used for the acylation of ghrelin.
Acylation↗
Identification of neuromedin S and its possible role in the mammalian circadian oscillator system.
The discovery of neuropeptides has resulted in an increased understanding of novel regulatory mechanisms of certain physiological phenomena. Here we identify a novel neuropeptide of 36 amino-acid residues in rat brain as an endogenous ligand for the orphan G protein-coupled receptor FM-4/TGR-1, which was identified to date as the neuromedin U (NMU) receptor, and designate this peptide 'neuromedin S (NMS)' because it is specifically expressed in the suprachiasmatic nuclei (SCN) of the hypothalamus. NMS shares a C-terminal core structure with NMU. The NMS precursor contains another novel peptide. NMS mRNA is highly expressed in the central nervous system, spleen and testis. In rat brain, NMS expression is restricted to the core of the SCN and has a diurnal peak under light/dark cycling, but remains stable under constant darkness. Intracerebroventricular administration of NMS in rats activates SCN neurons and induces nonphotic type phase shifts in the circadian rhythm of locomotor activity. These findings suggest that NMS in the SCN is implicated in the regulation of circadian rhythms through autocrine and/or paracrine actions.
Amino Acid Sequence↗
Synthetic examination of incorrectly proposed structures of biomolecules.
Many incorrect structures of biomolecules have been proposed for natural products. Synthesis of compounds having the proposed structures often enabled us to judge the correctness of the proposals. In some cases, we were able to revise the structures by synthesizing the biomolecules themselves. In other cases, we were able to definitely disprove the proposed structures. Some examples treated in this review include: auxin-a and b; the sex pheromone of Chlamydomonas; sex pheromones of the gypsy moth, the American cockroach, and the pink bollworm moth; Persoons' periplanone-A; orobanchol; naurol A; bifurcarenone; koninginin A; alpha-acoradiene; himachalene-type pheromones of the flea beetle; differolide; blattellastanoside A and B; etc.
Animals↗