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排序方式: 共有132条查询结果,搜索用时 15 毫秒
1.
K. Fujiki Yoshihiro Hotta Mutsuko Hayakawa Akio Saito Yukihiko Mashima Mikiro Mori Masaru Yoshii Akira Murakami Masayuki Matsumoto Seiji Hayasaka Nobuko Tagami Yasushi Isashiki Norio Ohba Atsushi Kanai 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》1999,237(9):735-740
· Background: Choroideremia (CHM) is an X-linked progressive dystrophy of the choroid, retinal pigment epithelium, and retina.
Recently, the REP-1 gene was isolated and the causative mutations in the gene were detected in patients with CHM. In a previous study, we described
a Japanese family with CHM who had a mutation in the REP-1 gene. In the present study, we performed extensive analysis of the REP-1 gene in patients with CHM from several institutions in Japan. · Methods: Twenty-six patients with CHM and 5 unaffected females
from 22 independently ascertained families were examined. Exons 1–15 of the REP-1 gene were screened by single-strand conformation polymorphism. The DNA fragments suspected of any variations were directly
sequenced. · Results: Fifteen different mutations, including one previously reported mutation, were detected in 18 families.
In addition, carrier status was proven in four unaffected females found to be heterozygous for the mutant allele. · Conclusions:
Fifteen different mutations of the REP-1 gene were detected in 18 Japanese families. There were no hot spots for the mutations and no missense mutations. The results
show that REP-1 gene defects cause CHM in Japanese patients, and the mutations in these Japanese patients differed from the mutations reported
for CHM patients in Europe, Canada, and America except for R267X and 1313delTC. These findings suggest that the mutations
occurred independently in the Japanese patients.
Received: 13 August 1998 Revised version received: 16 November 1998 Accepted: 9 December 1998 相似文献
2.
3.
Mukai T Mera K Nishida K Nakashima M Sasaki H Sakaeda T Nakamura J 《Biological & pharmaceutical bulletin》2002,25(11):1494-1497
Animal models prepared by treatment with toxic compounds such as a carbon tetrachloride have been used to examine drug disposition in hepatic diseases. However, it is possible that these compounds accumulate and cause damage to other organs as they are administered systemically. In this study, we used the liver surface application technique to deliver a toxic compound to the liver to prepare an appropriate animal model in which only the liver is significantly damaged. To restrict the absorption area in the liver, a cylindrical diffusion cell was attached to the liver surface of male Wistar rats. Twenty-four hours after direct addition of carbon tetrachloride to the diffusion cell, plasma levels of glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT), and hepatic malondialdehyde (MDA) concentration were increased, while there were no changes in plasma creatinine or renal MDA level. On the other hand, not only GOT, GPT and hepatic MDA, but also creatinine and renal MDA levels were markedly increased by p.o. and i.p. administration of carbon tetrachloride, suggesting renal damage. These results indicated that the animal models of liver damage prepared by utilizing drug delivery techniques to accumulate toxic compounds in the liver would enable us to investigate the precise effects of hepatic disorder on drug disposition. 相似文献
4.
Yamada M Chiba T Sasabe J Nawa M Tajima H Niikura T Terashita K Aiso S Kita Y Matsuoka M Nishimoto I 《Behavioural brain research》2005,164(2):139-146
Amyloid beta (Abeta) is closely related to the onset of Alzheimer's disease (AD). To construct AD animal models, a bolus administration of a large dose of toxic Abeta into the cerebral ventricles of rodents has been performed in earlier studies. In parallel, a continuous infusion system via an osmotic pump into the cerebral ventricle has been developed to make a rat AD model. In this study, we developed a mouse AD model by repetitive administration of Abeta25-35 via a cannula implanted into the cerebral ventricle. Using this administration system, we reproducibly constructed a mouse with impaired spatial working memory. In accordance with the occurrence of the abnormal mouse behavior, we found that the number of choline acetyltransferase (ChAT)-positive neurons was reduced in paraventricular regions of brains of Abeta25-35-administered mice in a dose-dependent manner. Considering that the repetitive administration of a small dose of toxic Abeta via an implanted cannula leads to a brain status more resembling that of the AD patients than a bolus injection of a large dose of Abeta, and therapeutic as well as toxic agents are able to be repeatedly and reliably administered via an implanted cannula, we concluded that the implanted cannula-bearing AD mouse model is useful for development of new AD therapy. 相似文献
5.
Nishida K Nose S Kuma A Mukai T Nakashima M Sasaki H Nakamura J 《The Journal of pharmacy and pharmacology》2004,56(5):683-687
The purpose of this study was to clarify the absorption characteristics of a drug across the mesenteric surface, which occupies a large area of absorption in the peritoneal cavity, in order to determine the drug absorption route after intraperitoneal administration. Absorption of phenolsulfonphthalein (PSP) as a model after application to the mesenteric surface was investigated in rats by employing a cylindrical diffusion cell attached to the mesentery with or without blood vessels. PSP was absorbed from the rat mesenteric surface, followed by its appearance in the plasma and bile, regardless of blood vessel existence. The absorption ratios of PSP in 6 h were calculated to be 92.1 and 83.6% from the mesenteric surface with and without blood vessels, respectively. We then employed an experimental system in which a polyethylene (PE) cap was stuck on the surface of the other side to exclude the influence of absorption of the drug from the other organ surfaces that penetrated across the mesentery. The PE cap decreased the appearance of PSP in the plasma from the mesenteric surface with blood vessels and eliminated the PSP absorption completely from the mesenteric surface without blood vessels. Accordingly, blood vessels on the mesenteric surface must actually play an important role in drug absorption, but the contribution of the mesenteric surface to drug absorption from the peritoneal cavity is unlikely to be significant because there is a small effective area of blood vessels. 相似文献
6.
In vivo gene transfection via intravitreal injection of cationic liposome/plasmid DNA complexes in rabbits 总被引:3,自引:0,他引:3
Kawakami S Harada A Sakanaka K Nishida K Nakamura J Sakaeda T Ichikawa N Nakashima M Sasaki H 《International journal of pharmaceutics》2004,278(2):255-262
To optimize the in vivo ocular transfection efficiency of plasmid DNA (pDNA)/cationic liposome complexes, N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA)/dioleoylphosphatidylethanolamine (DOPE) (1:1 molar ratio) liposomes and DOTMA/cholesterol (Chol) (1:1 molar ratio) liposomes were prepared with varying amounts of pDNA. pDNA/cationic liposome complexes were intravitreally injected (100 microL) in rabbits, and luciferase activity in the cornea, aqueous humor, iris-ciliary body, lens, vitreous body, and retina was measured. Transfection efficiency of pDNA alone did not change with pDNA ranging from 40 to 85 mg. In contrast, transfection efficiency of pDNA complexed with DOTMA/Chol liposomes significantly increased with the amount of pDNA ranging from 40 to 85 microg (P < 0.05). pDNA complexed with DOTMA/DOPE liposomes could not be prepared with pDNA greater than 60 microg. Among these experiments, pDNA (85 microg) complexed with DOTMA/Chol liposomes (pDNA:cationic liposome charge ratio (- : +) = 1.0:2.0) showed the highest transfection efficiency in the ocular tissue and its transfection-mediated luciferase activity peaked at 3 days. Among the ocular tissues, the highest gene expression was observed in the aqueous humor. 相似文献
7.
Nishida K Honda T Nakashima M Sasaki H Nakamura J 《Biological & pharmaceutical bulletin》2003,26(7):988-993
We have examined the influence of liver disease on drug absorption from the liver surface membrane, regarded as the first barrier for drug targeting to the liver. The main purpose of this study is to examine the possibility of direct liver surface application as a drug targeting method. We employed rats intoxicated with carbon tetrachloride (CCl(4)) or D-galactosamine (GAL) as the liver disease model, and examined drug absorption characteristics after application to the liver surface, by utilizing a cylindrical diffusion cell. In the liver-intoxicated rats, about 90% of a low molecular weight drug, phenolsulfonphthalein (PSP), as a model was absorbed from the liver surface in 6 h, similar to the normal rats (no treatment). Although the absorption rate was increased in the CCl(4) group, whereas slightly retarded absorption was observed in GAL group, there should be no serious problem for the clinical use of liver surface application. The PSP absorption from the liver surface in the CCl(4) group was indicated to obey first-order kinetics by elimination profile from the diffusion cell. The first-order absorption rate constant K(a) values of PSP from the liver surface, obtained by a compartment model and elimination profile, were increased 1.3-fold in the CCl(4) group compared to the control. Moreover, we performed drug application to the liver surface in the peritoneal cavity to assume clinical use. The K(a) of PSP in the CCl(4) group was about 4-fold larger than in the normal group, implying the importance of estimating changes in peritoneal drug absorption as a result of liver disease. Consequently, it is expected that there will be no marked decline in the absorption rate from the liver surface in a liver disease state, leading us to apply this administration method for liver targeting. 相似文献
8.
Takaishi M Ishisaki Z Yoshida T Takata Y Huh NH 《Brain research. Molecular brain research》2003,112(1-2):146-152
We examined the expression in the mouse brain of a recently isolated protein named calmin that has two calponin-homology domains in tandem at the N-terminus and a transmembrane domain at the C-terminus. Calmin mRNA and protein were detected in neurons of the hippocampus, cerebral cortex, and thalamus, Purkinje cells, and also in the choroid plexus and ependymal cells. The protein is present predominantly in dendrites and cell bodies of the neurons, but not in axons. Furthermore, the amounts of calmin mRNA and protein increase during the period of maturation of the mouse brain after birth, in a manner similar to that of PSD95 and synaptophysin. These results indicate that calmin may be involved in the development and/or maintenance of neuronal functions. 相似文献
9.
Kondoh T Amamoto N Doi T Hamada H Ogawa Y Nakashima M Sasaki H Aikawa K Tanaka T Aoki M Harada J Moriuchi H 《The Annals of pharmacotherapy》2005,39(3):563-566
OBJECTIVE: To report 2 cases of patients with Down syndrome and severe cognitive impairment who gained dramatic improvements in quality of life (QOL) upon donepezil treatment. CASE SUMMARIES: Case 1. A 38-year-old woman with Down syndrome, diagnosed with secondary progressive dementia when her mental state had deteriorated rapidly after graduation from junior high school, started donepezil treatment. The loading dose was 3 mg/day and was increased to 5 mg/day for maintenance. One month after the dose was increased, adverse effects such as soft stool and urinary incontinence appeared. These adverse effects disappeared when the dose was decreased again to 3 mg/day. Her QOL improved dramatically with this minimal dose. She recovered verbal and written communication skills that she had lost for the past 21 years. Case 2. A 22-year-old man with Down syndrome, who had been diagnosed as having severe mental retardation, was put on donepezil therapy. Both loading and maintenance doses were 3 mg/day. His QOL had also dramatically improved, with some recovery in verbal communication. Transient agitation/violence and transient muscle weakness appeared during the first few months of treatment. DISCUSSION: Patients with Down syndrome may be more sensitive to donepezil therapy than others and may benefit from this medicine, although they may also have adverse effects more frequently. CONCLUSIONS: Donepezil may be a useful medicine for some patients with Down syndrome with severe cognitive impairment or mental retardation if the adverse effects are manageable. 相似文献
10.
Tatsuya Mimura Mikiro Mori Hiroto Obata Tomohiko Usui Satoru Yamagami Hideharu Funatsu Hidetaka Noma Shiro Amano 《Acta ophthalmologica. Supplement》2012,90(8):773-782
Purpose: To assess the relationship between the prevalence and severity of conjunctivochalasis and pinguecula. Methods: Cross‐sectional, consecutive case study conducted at the university hospital of University of Tokyo Graduate School of Medicine. A total of 1061 patients aged from 1 to 94 years were enrolled. The grade and other parameters of conjunctivochalasis (classified into three locations: nasal, middle and temporal) and the grade of pinguecula located on the nasal or temporal conjunctiva were determined in all subjects. Patients were also divided into 5 or 10 age groups. Results: The severity of conjunctivochalasis affecting the nasal and temporal bulbar conjunctiva was significantly correlated with the grade of pinguecula located on the nasal and temporal conjunctiva in each age group (p < 0.05). Pinguecula was independently associated with conjunctivochalasis (nasal: odds ratio [OR] = 1.44; temporal: OR = 1.43) after adjustment for age. Conclusion: This was the first assessment of the relation between the grade of conjunctivochalasis and pinguecula in a large consecutive series of patients. Our results suggest that the prevalence and severity of conjunctivochalasis are related to the presence of pinguecula. 相似文献