Biomedical subjects
Publications and source records attributed to I Yamamoto.
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The pineal region is one of the surgically inaccessible areas in the brain. Many neurovascular structures form a formidable obstacle to the operative approach to this region. The approaches suitable for reaching the pineal region are the infratentorial supracerebellar, occipital transtentorial, posterior transcallosal, posterior transcortical and posterior subtemporal routes. Considerations important in selecting one of these surgical approaches are reviewed from the anatomical viewpoint.
Hemorrhagic cystitis (HC) is a major cause of morbidity after allogeneic bone marrow transplantation (BMT). Many therapies have been investigated to prevent or treat HC, but effective treatment for HC is still limited. While the efficacy of hyperbaric oxygen therapy has been established for HC due to chemotherapy and/or radiation therapy, its role in HC occurring after allogeneic BMT has yet to be defined. We report two cases of life-threatening late-onset HC after allogeneic BMT in children, which resolved after treatment with hyperbaric oxygen.
The cDNA of the phytochrome gene in the liverwort Marchantia paleacea var. diptera (MpdPHY1) was isolated. MpdPHY1 encoded a conventional phytochrome apoprotein. The MpdPHY1 transcript was accumulated in the dark and suppressed in the light. The degradation of the MpdPHY1 transcript by red light irradiation had red/far-red reversibility, suggesting that the liverwort phytochrome gene expression was regulated by a phytochrome. Northern blot analysis of the transcripts in cells irradiated by red/far-red light revealed that the liverwort phytochrome was involved in the expressions of chlB, chlL, chlN, or por, which encode subunits of light-independent and light-dependent protochlorophyllide oxidoreductase, respectively.
Four direct repeats of a 10-nt sequence, called dms boxes, are located upstream of the dmsCBA operon encoding dimethyl sulfoxide (DMSO) reductase in Rhodobacter sphaeroides f. sp. denitrificans IL106. Two dms boxes 1 and 2 have been shown to be binding sites of DmsR protein, a response regulator of a two-component system involved in the anaerobic induction by DMSO of DMSO reductase synthesis. In this study, functions of four dms boxes in the transcriptional regulation of the dmsCBA operon were investigated. The transcription start site of the dmsCBA genes was identified at the distance of 23 nt downstream of the closest dms box 4. Expression of the dmsC-lacZ gene fusion which included the dmsCBA promoter region containing the dms boxes was examined and its anaerobic induction by DMSO and DmsR-dependency were demonstrated in the phototroph. The examination with nucleotide substitutions in the four respective dms boxes showed that the set of four dms boxes is required for the dmsCBA operon activation. Moreover, the importance of the nucleotide sequence of TTCAC in dms box 4 and of A at the center in dms box 1 was significantly shown. These facts suggest that the pentad nucleotides TTCAC and TTAAC in the dms boxes serve as cis-acting elements in the transcriptional activation of the dmsCBA operon.
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OBJECTIVE: To investigate the safety and efficacy of liposomal fasudil in a sustained-release form for the prevention of cerebral vasospasm after subarachnoid hemorrhage (SAH). METHODS: Eighteen rats were divided into three groups, each of which received 2.5 mg/kg of liposomal fasudil, 5 mg/kg of liposomal fasudil, or drug-free liposomes after SAH. Next, experimental SAH was induced in 15 dogs by injection of autologous arterial blood into the cisterna magna twice after baseline vertebral angiography. In six dogs, 0.94 mg/kg of liposomal fasudil was injected into the cisterna magna (treatment group). In four dogs, drug-free liposomes were similarly injected (placebo group), and the remaining five dogs were not treated with liposomal injection after SAH (control group). Angiography was repeated on Day 7, and cerebrospinal fluid was collected before the dogs were killed. RESULTS: A high dose of liposomal fasudil caused no significant changes in mean arterial blood pressure and did not induce seizures during the observation period. Gross and microscopic examination of the brains revealed no abnormalities, but severe vasospasm was noted in the rat basilar artery, mainly in the group treated with drug-free liposomes. Likewise, in the canine placebo and control groups, significant vasospasm occurred in the basilar artery on Day 7. In the treatment group, vasospasm in the basilar artery was significantly ameliorated (P < 0.01). In vivo, 90% of fasudil was released from liposomes in the cerebrospinal fluid. CONCLUSION: A single injection of intrathecal liposomal fasudil is safe and effective for the prevention of vasospasm in experimental SAH.
Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) were studied in 75 patients with cerebral infarction. All patients were alert with the symptoms of hemiparesis and/or aphasia, and were divided into two groups: 42 patients had occlusion or stenosis of >75% at the internal carotid artery or main trunk of middle cerebral artery; and 33 patients did not. Hemispheric mean CBF was measured by performing first-pass radionuclide angiography using 99mTc-hexamethylpropylene amine oxime. CVR was measured as the percentage change from the baseline mean CBF value after the administration of 500 mg acetazolamide. The CVR in both groups was significantly impaired (5.2+/-6.3%, P<0.001 and 7.7+/-6.1%, P<0.01, respectively) compared with normal controls (14.7+/-3.3%), although the mean CBF was not significantly reduced compared with age-matched controls. In the 12 patients with unilateral carotid occlusion, five patients with good collateral flow via the anterior communicating artery showed preserved CVR (11.0+/-7.8%), but those without did not (1.6+/-7.0%). CVR is impaired in alert patients with cerebral infarction, although the mean CBF is not reduced, and good collateral flow via the anterior communicating artery in patients with carotid occlusion may be a sign of well-preserved haemodynamic status.
Since few previous studies have examined the effects of urocortin on physiological fed and fasted gastrointestinal motility, we administered urocortin intracerebroventricularly (icv) or intravenously (iv) in freely moving conscious rats and examined the changes in antral and duodenal motility. Icv and iv injection of urocortin disrupted fasted motor patterns of gastroduodenal motility, which were replaced by fed-like motor patterns. When urocortin was given icv and iv in the fed state, the motor activity remained like the fed patterns but % motor index (%MI) was decreased in the antrum and increased in the duodenum. Increase in the %MI in the duodenum induced by urocortin was shown as a nonpropagated event, since the transit of nonnutrient contents in the duodenum was decreased by icv and iv injection of urocortin. Changes in the gastroduodenal motility induced by icv injection of urocortin were abolished in animals with truncal vagotomy but not altered in animals with mechanical sympathectomy, suggesting that the vagal pathway may mediate the central action of urocortin. Neither urocortin antiserum nor alpha-helical CRF-(9-41) affected fed and fasted gastroduodenal motility, suggesting that endogenous urocortin is not involved in regulation of basal gastroduodenal motility.
BACKGROUND/AIM: Nitric oxide is a potent regulator of intrarenal hemodynamics and may influence the renal function. We investigated whether polymorphism of intron 4 of the endothelial constitutive nitric oxide synthase (ecNOS) gene is related to the progression of chronic renal failure. METHODS: Polymorphism of ecNOS intron 4 was studied in 1,005 hemodialysis patients (710 with nondiabetic nephropathy and 295 with diabetic nephropathy) and was compared with the findings in 189 healthy subjects. ecNOS genotypes were determined by the polymerase chain reaction, followed by agarose gel electrophoresis. RESULTS: The frequencies of ecNOS4a/a, ecNOS4a/b, and ecNOS4b/b genotypes were, respectively, 0% (0/189), 13.8% (26/189), and 86.2% (163/189) in the control group; 1.7% (12/710), 22.1% (157/710), and 76.2% (541/710) in the nondiabetic nephropathy group, and 1.0% (3/295), 22.7% (67/295), and 76.3% (225/295) in the diabetic nephropathy group. The frequency of ecNOS4a (ecNOSa/a and ecNOSa/b) was significantly higher in both the nondiabetic group and in the diabetic group than in the controls (p = 0.0025 and p = 0.0438, respectively). CONCLUSION: There was a significantly higher frequency of the a allele of intron 4 in both nondiabetic and diabetic hemodialysis patients, so the polymorphism of intron 4 of the ecNOS gene may have a wide influence on the progression of renal disease.
The genomic organization of Tcf23, the gene coding for mouse OUT, a basic helix-loop-helix transcription factor, was determined and its chromosome location was assigned to the A3 region of chromosome 5. By in silico searching, we further found the human counterpart of the mouse OUT gene (TCF23) in the draft human genome sequence and assigned it to 2p24-->p23.
Uridine analogue binding sites, the so-called uridine receptor, were observed in the experiments on specific [3H]N3-phenacyluridine binding to bovine synaptic membranes using two isomers, N3-(S)-(+)- and N3-(R)-(-)-alpha-hydroxy-beta-phenethyluridine, as ligands. The potent hypnotic, N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine, but not the (R)-isomer, strongly inhibited [3H]N3-phenacyluridine binding. The racemate had inhibitory activity intermediate between that of the two alpha-hydroxy-beta-phenethyluridines ((R)- or (S)-isomers). The inhibitory constants of these compounds were determined. The Ki values of N3-phenacyluridine, alpha-hydroxy-beta-phenethyluridine (racemate), N3-(R)-(-)-, and N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine were 0.65, 397.4, 1908, and 10.2 nM, respectively. The present results indicate the existence of uridine receptors in the central nervous system in relation to their hypnotic activities reported previously.
The synthetic route for a uterine relaxant, bis(2-[[(2S)-2-([(2R)-2-hydroxy-2-[4-hydroxy-3-(2-hydroxyethyl)-phenyl]ethyl]amino)-1,2,3,4-tetrahydronaphthalen-7-yl]oxy]-N,N-dimethylacetamide) sulfate (KUR-1246), was established by the coupling of optically active components, the bromohydrin 14 and the amine 24. We now describe the practical synthesis of these two optically active components. Bromohydrin 14 was obtained by the asymmetric borane reduction of the prochiral phenacyl bromide 13 using a catalyst prepared from aluminum triethoxide and a chiral amino alcohol. The other optically active component 24 was prepared from (S)-AMT.
2-O-alpha-D-Glucopyranosyl-6-O-octanoyl-L-ascorbic acid was enzymatically synthesized from 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G) and vinyl octanoate with a protease from Bacillus subtilis in pyridine. Furthermore, with various linear saturated fatty acid vinylesters as acyl donors, AA-2G was also converted to their corresponding 6-O-acyl AA-2G in the same manner. The reactivities of transacylation decreased with increasing length of the acyl groups. Thus, short chain acyl groups were transferred to AA-2G by this protease more efficiently than were long chain acyl groups. This enzymatic method is recommended for the synthesis of 6-Acyl-AA-2G with short or medium length chain acyl groups.
Methyl (2), ethyl (3), propyl (4), butyl (5), allyl (6), benzyl (7), o-, m-, p-xylyl (8-10), and alpha-phenylethyl (11) derivatives of arabinofuranosyluracil (1) were synthesized and their pharmacological effects in mice were examined by using hypnotic activity and synergism with pentobarbital as indices for the CNS depressant effects. At a dose of 2.0 micromol/mouse by intracerebroventricular injection, the values of mean sleeping time induced by 7-11 were 144, 154, 117, 33, and 34 min, respectively, whereas the alkyl (2-6) derivatives did not cause any hypnotic activity. N3-o-Xylylarabinofuranosyluracil (8) displayed the most potent hypnotic activity among the derivatives tested. Certain derivatives (6-11) significantly prolonged the pentobarbital-induced sleeping time compared to control. The present study indicated that substitution with benzyl and/or related groups on the N3-position of arabinofuranosyluracil produced CNS depressant effects.
Reaction of tri-O-acetyluridine (1) with benzyl bromide or 2-chloroacetophenone in the presence of K2CO3 gave the N3-substituted analogues 2a,c. Condensation of 1 with (+/-)-1-phenylethanol or 3,5-dimethylbenzyl alcohol using the Mitsunobu reaction also gave 2b,d in good yields. These compounds were allowed to react with Lawesson's reagent and were subsequently treated with ammonia to afford the 4-thiouracil derivatives 5a-d. Compounds 5a-c showed moderate hypnotic activity in mice. However, N3-(3,5-dimethyl)benzyl derivatives 3d, 5d were found to be almost inactive in this assay.
We describe the practical synthetic route for (2S)-7-methoxy-1,2,3,4-tetrahydro-2-naphthylamine 1(2S)-2-amino-7-methoxytetraline; (S)-AMT]. (2R)-2-(3-Methoxybenzyl)succinic acid [(R)-1] was obtained by the optical resolution of 2-(3-methoxybenzyl)succinic acid (1) as the salt of (1R,2S)-2-(benzylamino)cyclohexylmethanol (7), and (R)-1 was converted to the optically active (2S)-7-methoxy-1,2,3,4-tetrahydro-2-naphthoic acid [(S)-2] by the intramolecular Friedel-Crafts reaction followed by catalytic hydrogenation. (S)-AMT was obtained from the acid (S)-2 by Hofmann rearrangement without racemization.
The radical scavenging activity of the stable derivatives, which are O-substituted at the C-2 position of ascorbic acid (AA), against 1,1-diphenyl-2-picrylhydrazyl (DPPH) was evaluated in buffer under different pH conditions, and compared with those of AA and alpha-tocopherol. AA was shown to have 50% radical scavenging ability (EC50) at a concentration of 2.2 x 10(-5) M against 0.1 mM DPPH in 60% ethanol. Ascorbyl 6-palmitate, a lipophilic AA derivative which has a free endiol group and is therefore unstable, also showed potent radical scavenging activity with EC50 of 2.9 x 10(-5) M. A typical lipophilic antioxidant, alpha-tocopherol gave a similar EC50 value as that of AA. In contrast, ascorbyl 2,6-dipalmitate, AA 2-phosphate and AA 2-sulfate exhibited negligible scavenging activity. On the other hand, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G) and a series of 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids (6-Acyl-AA-2G) themselves exhibited the radical scavenging activity of EC50: 6.1 x 10(-5) M and 4.4 x 10(-5)-5.9 x 10(-5) M, respectively, although their activities were lower than that of AA. Among 6-Acyl-AA-2G derivatives, the EC50 values tended to decrease with increasing length of their acyl carbon group. Increasing pH of the buffer resulted in decrease in the scavenging activity of all compounds tested as expected. We speculate that the difference in the radical scavenging activity of derivatives O-substituted at the C-2 position of AA may be ascribed to the linkage type of the substituent group to the endiol-lactone resonance system and the degree of dissociation of the C-3 proton.