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91.
Nakazato A Ohta K Sekiguchi Y Okuyama S Chaki S Kawashima Y Hatayama K 《Journal of medicinal chemistry》1999,42(6):1076-1087
sigma Receptor antagonists may be effective antipsychotic drugs that do not induce motor side effects caused by ingestion of classical drugs such as haloperidol. We obtained evidence that 1-(2-dipropylaminoethyl)-4-methoxy-6H-dibenzo[b,d]pyran hydrochloride 2a had selective affinity for sigma receptor over dopamine D2 receptor. This compound was designed to eliminate two bonds of apomorphine 1 to produce structural flexibility for the nitrogen atom and to bridge two benzene rings with a -CH2O- bond to maintain the planar structure. In light of the evidence, N, N-dipropyl-2-(4-methoxy-3-benzyloxylphenyl)ethylamine hydrochloride 10b was designed. Since compound 10b had eliminated a biphenyl bond of 6H-dibenzo[b,d]pyran derivative 2a, it might be more released from the rigid structure of apomorphine 1 than compound 2a. The chemical modification of compound 10b led to the discovery that N, N-dipropyl-2- [4-methoxy-3-(2-phenylethoxyl)phenyl]ethylamine hydrochloride 10g (NE- 100), the best compound among arylalkoxyphenylalkylamine derivatives 3, had a high and selective affinity for sigma receptor and had a potent activity in an animal model when the drug was given orally. We report here the design, synthesis, structure-activity relationships, and biological characterization of novel arylalkoxyphenylalkylamine derivatives 3. 相似文献
92.
The reductive debromination of the hypnotic (alpha-bromoiso-valeryl)urea to (3-methylbutyryl)urea by intestinal bacteria has been studied. The caecal contents of rats, mice, hamsters, guinea-pigs and rabbits had significant debrominating activity toward (alpha-bromoiso-valeryl)urea. The cell-free extract of intestinal bacteria from the caecal contents of rats had debrominating activity in the presence of both flavin mononucleotide (FMN) and NADH (or NADPH) under anaerobic conditions. Seven pure strains of intestinal bacteria were also tested and the highest activity was observed with Clostridium sporogenes. The cell-free extract of Clostridium sporogenes had debrominating activity in the presence of both FMN and NADH (or NADPH), and this activity was inhibited by sodium arsenite and potassium cyanide. The activity of the cell-free extract was also supported by the photochemically reduced form of FMN. The debromination in intestinal bacteria seems to proceed in two steps--reduction of flavins by bacterial flavin reductase(s) in the presence of NADPH or NADH, and then the reductive debromination of (alpha-bromoiso-valeryl)urea to (3-methylbutyryl)urea by bacterial dehalogenase(s) using the reduced flavins as an electron donor. These results indicate that intestinal bacteria play a role in the reductive debromination of (alpha-bromoiso-valeryl)urea to (3-methylbutyryl)urea in animals. The debromination is inhibited by oxygen and dependent on flavins. 相似文献
93.
The reductive metabolism in vivo of a flavoring additive, trans-4-phenyl-3-buten-2-one (PBO; trans-methyl styryl ketone) was investigated in rats and dogs. In both species, the double bond-reduced product, 4-phenyl-2-butanone (PBA), was detected by HPLC as the predominant species in blood after i.v. administration of PBO. PBA detected in rat blood was identified by comparison to the authentic sample. In contrast, the carbonyl-reduced product, trans-4-phenyl-3-buten-2-ol (PBOL) was also detected as a minor metabolite of PBO in both species. The area under the curve of PBOL in rat blood was only 3% of that of PBA. PBO was mutagenic in the Ames test using Salmonella typhimurium TA 100 when S-9 mix was added, but PBA and PBOL were not. It appears that PBO is mainly metabolized to PBA in vivo in rats and dogs as a detoxification pathway. 相似文献
94.
Chromatographic and spectrometric discrimination of fentanyl and its 24 analogues are discussed. Twenty-three of 25 samples were discriminated from each other by gas chromatography (GC), and the combination of GC and mass spectrometry enabled discrimination of all 25 samples. Condensed-phase infrared spectrometry was also useful for the differentiation of structurally similar compounds, but vapor-phase infrared spectra were not useful for discrimination of fentanyls. 相似文献
95.
Toshi Nomura Katsuhiro Inoue Cyrus R. Creveling Fuhito Komatsu Norio Ohta Takehiro Chino Nobuyuki Karasawa Ikuko Nagatsu 《Brain research》1996,735(2):314
Relatively large amounts of DOPA as compared with the concentration of norepinephrine are found in human dental pulp. AADC and COMT are localized in blood vessel walls of human dental pulp. This localization suggests a functional relationship between COMT and AADC with regard to the metabolism of DOPA. 相似文献
96.
Increased levels of urinary interleukin-6 in Kawasaki disease 总被引:4,自引:0,他引:4
K. Ohta A. Seno N. Shintani E. Kato A. Yachie H. Seki T. Miyawaki N. Taniguchi 《European journal of pediatrics》1993,152(8):647-649
Kawasaki disease (KD) often presents with abnormal urinary findings, such as aseptic pyuria, mild proteinuria and microscopic haematuria. In this study, we measured urinary interleukin-6 (IL-6) by a sensitive sandwich ELISA assay using mouse monoclonal antibodies against recombinant IL-6 to elucidate the role of IL-6 in the pathogenesis of renal lesions in KD. Serum IL-6 levels were increased in acute KD as well as in febrile controls. Importantly, urinary IL-6 levels were consistently elevated in patients with acute KD, but much lower in febrile controls. Urinary IL-6 levels returned steadily to normal during the convalescent phase. In addition to IL-6, urinary levels ofN-acetyl--d-glucosaminidase (NAG) and 2-microglobulin (2-mg) were also elevated during the acute phase of this disease. Eosinophils and macrophages were identifiable in urinary sediments from these patients. The increased levels of urinary IL-6 in combination with increased NAG and 2-mg seemed to suggest the presence of certain renal parenchymal lesions with cellular infiltration during the acute phase of the disease. IL-6 may serve as clinically useful parameter for the detection and monitoring of the renal involvement in KD. 相似文献
97.
T. Morioka T. Matsushima K. Ikezaki S. Nagata M. Ohta K. Hasuo M. Fukui 《Neuroradiology》1993,35(6):462-465
Two cases of intracranial adenoid cystic carcinoma mimicking meningioma are reported. In one, MRI showed not only a homogeneously enhancing extra-axial tumour attached to the dura mater of the posterior cranial fossa, but also surrounding dural enhancement, the dural tail sign. In the second, CT demonstrated a well-demarcated enhancing extra-axial tumour, indistinguishable from a sphenoid ridge meningioma extending into the orbit. The neuroradiological features of intracranial adenoid cystic carcinoma may thus closely resemble those of meningioma. 相似文献
98.
Kayahara M Nagakawa T Ueno K Ohta T Kanno M Nakano T Mori K Takeda T Miyazaki I 《International journal of oncology》1992,1(3):319-323
Forty patients underwent surgical resection for cancer of the middle and distal bile duct. Nineteen patients underwent a curative resection with 3- and 5-year survival rates of 63% and 48%, respectively. None of the patients who underwent a palliative resection survived two years. The factor most strongly associated with recurrence was the presence of tumor in the surgical margin. Recurrence was frequent in patients with disease in the middle portion of the bile duct who underwent extrahepatic biliary resection with choledochojejunostomy, while lower bile duct cancer was associated with peri-aortic or retroperitoneal recurrence. Pancreatoduodenectomy, with combined resection of the portal vein in middle bile duct cancer, regional lymphadenectomy, including peri-aortic lymph nodes and nerve plexus is required for curative resection of middle and distal biliary carcinoma beyond the early noninvasive stage. 相似文献
99.
J Hanakita H Suwa S Nagayasu S Nishi F Ohta H Sakaida 《Neurologia medico-chirurgica》1991,31(13):936-942
Thoracic lesions present several clinical problems, particularly in their diagnosis and treatment, compared with cervical or lumbar lesions. Since 1983, 18 cases of thoracic space lesions, excluding spinal tumors or trauma have been experienced: nine cases of ossification of yellow ligament (OYL), five of ossification of posterior longitudinal ligament (OPLL), and four of disc hernia (DH). In these 18 patients, problems of clinical manifestations, neuroradiological examination, and surgical approaches are analyzed and discussed. As clinical manifestations, there was a preponderant occurrence in males in the OYL group, while in the OPLL group all the patients were females. OYL and DH occurred at lower thoracic levels. Thirteen of the 18 patients showed combined lesions either in the cervical or in the lumbar regions, such as cervical OPLL, cervical spondylosis, lumbar DH, and lumbar canal stenosis. In the neuroradiological examinations diagnosis of the upper thoracic lesions was difficult. Computed tomography (CT) scan with intrathecal metrizamide injection seemed essential for examination of ossified thoracic lesions. However, because CT imaging of the entire spine is impractical, efficient use of this examination requires previous localization of the offending vertebral level from either the neurological findings or other neuroradiological examinations such as myelography. Magnetic resonance imaging seemed most useful for ruling out the thoracic compressing lesions. As for surgical approaches, posterior decompression was effective for OYL and the anterior approach was useful for OPLL and DH. In patients with "tandem lesions," neurological and neuroradiological findings played an important role in deciding the responsible site. 相似文献
100.
Clinical observations of juvenile nonprogressive muscular atrophy localized in hand and forearm 总被引:2,自引:0,他引:2
Osamu Hashimoto Masahiro Asada Michiya Ohta Yoshigoro Kuroiwa 《Journal of neurology》1976,211(2):105-110
Summary Twenty-seven patients with juvenile nonprogressive muscular atrophy localized in the hand and forearm were analyzed. The clinical characteristics were juvenile male occurrence, insidious onset, specific distribution of localized muscular atrophy and a stationary course. On electromyography, denervation voltage (or giant NMU) is found in the atrophied muscles and sometimes in contralateral nonatrophied ones. Sensory disturbance was not remarkable. Although the etiological factor was not known, strenuous exercise of arms in sports was noted frequently in the history.
Zusammenfassung 27 Patienten mit juveniler nonprogressiver Muskelatrophie, lokalisiert an der Hand und dem Vorderarm wurden analysiert. Klinisch charakteristische Merkmale waren Vorkommen bei jungen Männern, schleichender Beginn, lokalisierter Befall der erwähnten Muskelgruppe und stationärer Verlauf nach einer anfänglichen Progression. Elektromyographisch wurde eine Denervation in den atrophischen Muskeln und manchmal in den Muskeln der kontralateralen Seite bemerkt. Sensible Ausfälle waren nicht eindrücklich. Obgleich die Ätiologie nicht klar war, wurde häufiger Gebrauch der Hand im Sport in der Krankheitsgeschichte bemerkt.相似文献