The direct and enantioselective, one-pot, three-component, cross-mannich reaction of aldehydes.
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Journal Article↗
Biomedical subjects
Yujiro Hayashi
Publications and source records attributed to Yujiro Hayashi.
Asymmetric total synthesis of pseurotin A.
The asymmetric total syntheses of pseurotin A and 8-O-demethylpseurotin A have been accomplished. Key reactions are a NaH-promoted intramolecular cyclization of an alkynylamide to form a gamma-lactam, an aldol reaction of a benzylidene-substituted ketone, and the late-stage introduction of the benzoyl group by a selective oxidation of a benzylidene moiety with dimethyldioxirane (DMD). [reaction: see text]
Benzylidene Compounds↗
Growth hormone secretagogue receptor expression in the cells of the stomach-projected afferent nerve in the rat nodose ganglion.
Growth hormone secretagogue receptor (GHS-R) is widely expressed in various regions of the body, such as the brain, pituitary gland, heart and gastrointestinal tract. Recently, ghrelin, an endogenous ligand for GHS-R, was found in the rat stomach, and several studies have suggested that ghrelin acts via the vagal afferent nerve. In this study, we studied the expression of GHS-R mRNA in the rat nodose ganglion by reverse transcriptase-polymerase chain reaction and in situ hybridization, the results of which clearly demonstrated the presence of GHS-R mRNA and GHS-R producing cells in the rat nodose ganglion. We also studied the retrograde tracing of nodose ganglion cells to the stomach and found that some GHS-R mRNA-expressing cells contain the retrograde rebelling. Our results provide direct morphological evidence that GHS-R is produced in afferent neurons of the nodose ganglion and suggest that ghrelin signals from the stomach are transmitted to the brain via vagal afferent nerves.
Afferent Pathways↗
Existence of ghrelin-immunopositive and -expressing cells in the proventriculus of the hatching and adult chicken.
Ghrelin was isolated from the rat stomach as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R) and has been found in the gastrointestinal tract of many vertebrates. Although the sequence and structure of chicken ghrelin has recently been determined, morphological characteristics of ghrelin cells in the chicken gastrointestinal tract are still obscure. In this study, we investigated ghrelin expression and distribution of ghrelin-producing cells in the hatching and adult chicken gastrointestinal tract by RT-PCR, immunohistochemistry and in situ hybridization. Ghrelin mRNA expression was observed mainly in the proventriculus in the hatching chicken and in the proventriculus, pylorus and duodenum of the adult chicken by RT-PCR. Ghrelin-immunopositive (ghrelin-ip) cells in the proventriculus were located at the mucosal layer but not in the myenteric plexus or smooth muscle layer. The number of ghrelin-ip cells in the adult chicken was greater than that in the hatching chicken. Interestingly, in the adult chicken, the number of ghrelin-ip cells were almost the same as that of ghrelin mRNA-expressing (ghrelin-ex) cells; however, in the hatching chicken, the number of ghrelin-ex cells was greater than that of ghrelin-ip cells. These results clearly demonstrate that ghrelin-producing cells exist in the chicken gastrointestinal tract, especially in the proventriculus, from hatching to adult stages of development, as well as in mammals.
Animals↗
Anti-cachectic effect of ghrelin in nude mice bearing human melanoma cells.
Ghrelin is a novel brain-gut peptide that stimulates food intake and body weight gain. We studied the anabolic effect of ghrelin in a cancer cachexia mouse model. SEKI, a human melanoma cell line, was inoculated into nude mice to examine the effects of ghrelin on food intake and body weight. The intraperitoneal administration of ghrelin twice a day (6 nmol/mice/day) for 6 days suppressed weight loss in SEKI-inoculated mice and increased the rate of weight gain in vehicle-treated nude mice. Ghrelin administration also increased food intake in both SEKI- and vehicle-treated mice. Both the weight of white adipose tissue and the plasma leptin concentration were reduced in tumor-inoculated mice compared with vehicle-treated mice; these factors increased following ghrelin administration. The levels of both ghrelin peptide and mRNA in the stomach were upregulated in tumor-inoculated mice. The anabolic effect of ghrelin efficiently reverses the cachexia in mice bearing SEKI human melanoma. Ghrelin therefore may have a therapeutic ability to ameliorate cancer cachexia.
Animals↗
Compensatory changes in static and dynamic subjective visual vertical in patients following vestibular schwanoma surgery.
OBJECTIVE: Among patients with vestibular schwanoma (VS), vestibular function is nonhomogeneous, both before and after surgical removal of the VS. This paper reports investigations of neural changes, especially changes in the contribution of visual input to vestibular system integration, after VS surgery. METHODS: We examined 33 patients who underwent VS surgery via a middle fossa approach. Static and dynamic subjective visual vertical (SVV) was measured once after surgery and compared to those measured in control subjects. SVVs were assessed using a paradigm requiring the subject to manually adjust an image of a bar to the perceived vertical alignment. SVVs were measured when the background was stationary or rotating. RESULTS: In almost all patients, static SVV deviated toward the operated side. In VS subjects, the mean static SVV was 1.8+/-2.2 degrees; the amount of deviation in the dynamic SVV toward the operated side (11.7+/-8.3 degrees ) was significantly larger than that to the intact side (8.8+/-5.5 degrees ). In VS subjects, static SVV was correlated with dynamic SVV only in cases of bar adjustments toward the operated side (R=0.67, P<0.001), but not in cases of adjustments toward the intact, unoperated side. The axis of rotation was defined as the mean value of dynamic SVV for adjustments toward either side. There was only a weak correlation between the static SVV and the axis of rotation (R=0.31; P<0.05) in the control subjects. On the other hand, a more robust correlation between static SVV and axis of rotation was found (R=0.67, P<0.001) in VS subjects. There was no correlation between the static SVV and the deviation of dynamic SVV from static SVV for CCW and CW in control subjects. In contrast, there were significant correlations between static SVV and deviation of dynamic SVV from static SVV for adjustments made toward both operated (r=0.48, P<0.001) and intact sides (r=038, P<0.05). CONCLUSION: It is assumed that the amount of deviation in static SVV reflects the individual level of compensation. In addition, increased visual dependency evoked a symmetrical bias of the dynamic SVV from the measures at initial SVV assessment (i.e. static SVV or the center of tilt). As a result, we conclude that the contribution of visual inputs had changed after surgery, while at the same time, each patient used their static SVV as their reference point for orientation.
Adaptation, Physiological↗
Diastereoselective total synthesis of both enantiomers of epolactaene.
A stereocontrolled total synthesis of both the (+)- and (-)-epolactaene ((+)- and (-)-1) enantiomers from tetrahydropyran-2-ol is described. The following reactions in this synthesis are particularly noteworthy: (1) the stereoselective construction of the conjugated (E,E,E)-triene by a combination of kinetic deprotonation and thermodynamic equilibration, (2) the E-selective Knoevenagel condensation of beta-ketonitrile 33 with a chiral 2-alkoxyaldehyde, (3) a diastereoselective epoxidation achieved using a bulky nucleophile (TrOOLi) and an appropriate protecting group, (4) the mild hydrolysis of an alpha-epoxy nitrile by silica gel on TLC facilitated by hydroxyl-mediated, intramolecular assistance.
Chromatography, Thin Layer↗
The HfCl4-mediated Diels-Alder reaction of furan.
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Journal Article↗
Asymmetric total synthesis of (-)-azaspirene, a novel angiogenesis inhibitor.
The asymmetric total synthesis of (-)-azaspirene, an angiogenesis inhibitor, has been accomplished, establishing its absolute stereochemistry. The key steps are a MgBr2.OEt2-mediated, diastereoselective Mukaiyama aldol reaction, a NaH-promoted, intramolecular cyclization of an alkynylamide, and the aldol reaction of a ketone containing functionalized gamma-lactam moiety without protection of tert-alcohol and amide functionalities.
Angiogenesis Inhibitors↗
Total synthesis of (+)-epoxyquinols A and B.
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Angiogenesis Inhibitors↗
A novel adenine nucleotide translocase inhibitor, MT-21, induces cytochrome c release by a mitochondrial permeability transition-independent mechanism.
The release of cytochrome c from mitochondria is a critical step during apoptosis. In order to study this process, we have used a synthetic compound, MT-21, that is able to initiate release of cytochrome c from isolated mitochondria. We demonstrate that MT-21 significantly inhibits ADP transport activity in mitochondria and reduces binding of the adenine nucleotide translocase (ANT) to a phenylarsine oxide affinity matrix. These results suggest that ANT, one of the components of the mitochondrial permeability transition (PT) pore, is the molecular target for MT-21. In agreement with this, the MT-21-induced cytochrome c release was effectively inhibited in the presence of ANT ligands, and MT-21 could dissociate ANT from a complex with a glutathione S-transferase-cyclophilin D fusion protein. Interestingly, we also found that specific inhibitors of ANT such as MT-21 and atractyloside could induce cytochrome c release without mitochondrial swelling and that this event was highly dependent on the presence of Mg(2+). These results suggest that although ANT resides in the mitochondrial inner membrane, specific ANT inhibitors can induce cytochrome c release without having an effect on inner membrane permeability. Therefore, MT-21 can be a powerful tool for studying the mechanism of PT-independent cytochrome c release from mitochondria.
Cloning, Molecular↗
Three-dimensional analysis of nystagmus in benign paroxysmal positional vertigo. New insights into its pathophysiology.
Nystagmus is a rhythmical rotation of the eyeball. Its characteristics can be defined mathematically by the axis of rotation and the angular velocity around this axis. We analysed the axis of rotation for the nystagmus in benign paroxysmal positional vertigo (BPPV) to elucidate its pathophysiology. Thirteen patients with typical unilateral BPPV participated in the present study. The axis of rotation for the nystagmus was calculated from images recorded on digital videotape with an infrared CCD camera, using an algorithm that we developed. The patients' responsiveness to Semont's liberatory maneuver was also assessed.The results showed that patients could be assigned to one of two groups based on the rotation axis of the nystagmus. In one group of patients (n = 7; Group A), the axis of rotation was almost vertical to the plane containing the posterior semicircular canal (PSC) on the presumed affected side. In the other group of patients (n = 6; Group B), it was clustered around the naso-occipital axis. These results suggest that in the patients in Group A the responsible lesion is confined to the PSC, whereas the pathogenesis underlying the conditions in those in Group B is considered to be more complicated. This speculation was reinforced by the difference in responsiveness to Semont's liveratory maneuver. All of the patients in Group A showed remission of vertigo within 10 days (mean, 2.4 days) after onset of treatment using Semont's liberatory maneuver, whereas the patients in Group B required much longer periods of time for remission to occur (mean, 25.7 days). Our findings lead to the conclusion that by considering the spatial orientation of individual semicircular canals, in the patients in Group B the pathophysiology is not confined to the PSC, but most probably all three semicircular canals are involved.
Adult↗
Dynamic and static subjective visual vertical with aging.
OBJECTIVE: Our vestibular function is gradually deteriorating during aging, although, its behavioral consequences are not easily recognized due to a substitution process by other sensory modalities as visual or proprioceptive inputs. METHODS: To reveal such a hidden substitution process by visual signals, the measurement of the static as well as the dynamic subjective visual vertical (SVV) was performed among 63 healthy subjects of different age. RESULTS: The static SVV was found to be stable among all subjects, whereas the shift of the dynamic SVV during rotation of a background scene gradually increased with age. CONCLUSION: This result indicates that the substitution process identified as a function of age in a perceptual test may have its counterpart in postural stabilizing reflex.
Adult↗