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R Koide

Publications and source records attributed to R Koide.

At least 55 records · Page 3Linked to original sources
PubMed1996

Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant, neurodegenerative disorder that affects the cerebellum and other areas of the central nervous system. We have devised a novel strategy, the direct identification of repeat expansion and cloning technique (DIRECT), which allows selective detection of expanded CAG repeats and cloning of the genes involved. By applying DIRECT, we identified an expanded CAG repeat of the gene for SCA2. CAG repeats of normal alleles range in size from 15 to 24 repeat units, while those of SCA2 chromosomes are expanded to 35 to 59 repeat units. The SCA2 cDNA is predicted to code for 1,313 amino acids-with the CAG repeats coding for a polyglutamine tract. DIRECT is a robust strategy for identification of pathologically expanded trinucleotide repeats and will dramatically accelerate the search for causative genes of neuropsychiatric diseases caused by trinucleotide repeat expansions.

Amino Acid Sequence↗
PubMed1996

Non-Mendelian transmission in dentatorubral-pallidoluysian atrophy and Machado-Joseph disease: the mutant allele is preferentially transmitted in male meiosis.

Autosomal dominant dentatorubral-pallidoluysian atrophy (DRPLA) and Machado-Joseph disease (MJD) are neurodegenerative disorders caused by CAG trinucleotide repeat expansions. An inverse correlation of age at onset with the length of the expanded CAG trinucleotide repeats has been demonstrated, and the intergenerational instability of the length of the CAG trinucleotide repeats, which is more prominent in paternal than in maternal transmissions, has been shown to underlie the basic mechanisms of anticipation in DRPLA and MJD. Our previous observations on DRPLA and MJD pedigrees, as well as a review of the literature, have suggested that the numbers of affected offspring exceed those of unaffected offspring, which is difficult to explain by the Mendelian principle of random segregation of alleles. In the present study, we analyzed the segregation patterns in 211 transmissions in 24 DRPLA pedigrees and 80 transmissions in 7 MJD pedigrees, with the diagnoses confirmed by molecular testing. Significant distortions in favor of transmission of the mutant alleles were found in male meiosis, where the mutant alleles were transmitted to 62% of all offspring in DRPLA (chi2 = 7.69; P<.01) and 73% in MJD (chi2 = 6.82; P<.01). The results were consistent with meiotic drive in DRPLA and MJD. Since more prominent meiotic instability of the length of the CAG trinucleotide repeats is observed in male meiosis than in female meiosis and meiotic drive is observed only in male meiosis, these results raise the possibility that a common molecular mechanism underlies the meiotic drive and the meiotic instability in male meiosis.

Adolescent↗
PubMed1996

Somatic mosaicism of expanded CAG repeats in brains of patients with dentatorubral-pallidoluysian atrophy: cellular population-dependent dynamics of mitotic instability.

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disease caused by unstable expansion of a CAG repeat in the DRPLA gene. We performed detailed quantitative analysis of the size and the size distribution (range) of the expanded CAG repeats in various regions of the CNS of eight autopsied patients with DRPLA. Expanded alleles (AE) showed considerable variations in size, as well as in range, depending on the region of the CNS, whereas normal alleles did not show such variations, which indicates the occurrence of somatic mosaicism of AE in the CNS. The AE in the cerebellar cortex were consistently smaller by two to five repeat units than those in the cerebellar white matter. Moreover, the AE in the cerebral cortex were smaller by one to four repeat units than those in the cerebral white matter. These results suggest that the smaller AE in the cerebellar and cerebral cortices represent those of neuronal cells. The ranges of the AE in the cerebral cortex, cerebral white matter, and cerebellar white matter showed considerable variation ranging from 9 to 23 repeat units, whereas those in the cerebellar cortex showed little variance and were approximately 7 repeat units. The ranges of the AE in the cerebral cortex, cerebral white matter, and cerebellar white matter were much broader in patients with higher ages at death than they were in patients with lower ages at death, raising the possibility that the range of AE increases with time, as the result of mitotic instability of AE.

Adult↗
PubMed1996

[Pharmacokinetics of norfloxacin and lomefloxacin in aqueous humour analysed by microdialysis].

The pharmacokinetics of norfloxacin (NFLX) and lomefloxacin (LFLX) in rabbit aqueous humour after instillation of 0.3% solution (20 microliters) and oral administration (20 mg/kg) were investigated by microdialysis. We also measured plasma concentration of fluoroquinolones after oral administration. After instillation, the maximum concentration (Cmax) of NFLX and LFLX in the aqueous humour was 0.80 and 1.20 micrograms/ml, and elimination half time (t1/2) was 130 and 96 min, respectively. After oral administration, the Cmax in plasma of NFLX and LFLX was 2.06 and 1.89 micrograms/ml, and the Cmax in aqueous humour was 0.16 and 0.62 microgram/ml, respectively. t1/2 of NFLX in aqueous humour and plasma was 225 and 295 min, and t1/2 of LFLX was 188 and 175 min, respectively. The ratio of aqueous humour/serum concentration of NFLX and LFLX was 7.8 and 35.3% 4 hrs after oral administration. These results suggest that, after instillation, LFLX penetrated better into the aqueous humour, and was eliminated faster, than NFLX, and that after oral administration, NFLX could not panetrate well into the aqueous humor from the blood.

Animals↗
PubMed1995

Dentatorubral-pallidoluysian atrophy: clinical features are closely related to unstable expansions of trinucleotide (CAG) repeat.

Dentatorubral-pallidoluysian atrophy is an autosomal dominant neurodegenerative disease characterized by various combinations of ataxia, choreoathetosis, myoclonus, epilepsy, and dementia as well as a wide range of ages at onset. A specific unstable trinucleotide repeat expansion in a gene on the short arm of chromosome 12 was recently identified as the pathogenic mutation for this disease. We investigated how the degree of expansion of the CAG repeat effects the clinical manifestations of dentatorubral-pallidoluysian atrophy. The size of the expanded alleles was well correlated with the age at onset (r = -0.696, p < 0.001). Patients with the progressive myoclonus epilepsy phenotype had larger expansions (62-79 repeats) and an earlier age at onset (onset before age 21). Furthermore, most of the patients with the progressive myoclonus epilepsy phenotype inherited their expanded alleles from their affected fathers. On the other hand, patients with the non-progressive myoclonus epilepsy phenotype showed smaller expansions (54-67 repeats) and a later age at onset (onset at or after age 21). Detailed analyses of clinical features demonstrated that ataxia, involuntary movement of either myoclonus or choreoathetosis, and intellectual decline are cardinal features of dentatorubral-pallidoluysian atrophy, with myoclonus and epilepsy being observed more frequently in patients with an earlier age at onset. Thus the wide variation in clinical manifestations of dentatorubral-pallidoluysian atrophy can now be clearly explained based on the degree of CAG repeat expansion, which strongly indicates that the expanded alleles are intimately involved in the neuronal degeneration in dentatofugal and pallidofugal systems.

Adolescent↗
PubMed1995

Dentatorubral-pallidoluysian atrophy (DRPLA): close correlation of CAG repeat expansions with the wide spectrum of clinical presentations and prominent anticipation.

Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disease characterized by various combinations of ataxia, choreoathetosis, myoclonus, epilepsy and dementia as well as various ages of onset. We have identified a specific unstable trinucleotide repeat expansion in a gene on the short arm of chromosome 12 as the pathogenic mutation for DRPLA. We investigated how the degree of the expansion of the CAG repeat affects the clinical manifestations of DRPLA. The sizes of the expanded alleles were well correlated with the ages of onset (r = -0.6955, P < 0.001). Patients with progressive myoclonus epilepsy (PME) phenotype had larger expansions (62-79 repeats) and earlier ages of onset (onset before age 20). Furthermore, most of the patients with PME phenotype inherited their expanded alleles from their affected fathers. On the other hand, patients with non-PME phenotype showed later ages of onset (onset after age 20) and smaller expansions (54-67 repeats). When ages of onset of each clinical symptoms are compared with sizes of the CAG repeat, there is again a remarkably high correlation of the sizes of CAG repeat with each of the clinical symptoms. Thus the wide variation in clinical manifestations of DRPLA can now be clearly explained based on the degree of CAG repeat expansion, which strongly indicates that the expanded alleles are intimately involved in the neuronal degeneration in dentatofugal and pallidofugal systems.

Adult↗
PubMed1995

[Central ocular hypotensive effect of noradrenaline].

We investigated the effects of topical and central administration of noradrenaline (NA) on the intraocular pressure (IOP) in pigmented rabbits. Unilateral instillation of NA (200 micrograms) produced no significant change in IOP. On the other hand, intracerebroventricular (ICV) administration of NA (0.01-1 micrograms) decreased IOP in both eyes in a dose-related fashion. The ocular hypotensive effect of NA was diminished by sympathectomy of the superior cervical sympathetic nerve or by ICV pretreatment with yohimbine hydrochloride 1-10 micrograms). These results suggest that the hypotensive effects of contrally administered NA might be mediated by alpha 2-adrenoceptor stimulation in the central nervous system.

Administration, Topical↗
PubMed1995

[An intraocular lens power calculation for high myopia].

The accuracy of intraocular lens power calculation formulas for the axial high myopia were examined, especially regarding the point of the predictive refraction. We examined 170 eyes with axial lengths of 27 mm or longer, with postoperative visual acuity of 0.5 or more, and postoperative astigmatism of less than +/- 2D. Five formulas were tested for accuracy in predicting postoperative refraction. They were the L-SRK, SRK, SRK II, SRK/T, and Binkhorst formulas. The SRK formula tended to predict less myopia than the actual postoperative refraction. The SRK II and Binkhorst formulas predicted more myopia than the actual postoperative refraction. The best results were produced by the L-SRK and SRK/T formulas. The accuracy of the L-SRK formula predictions were measured for each of the four myopic levels. The same was done for the SRK/T formula. For both formulas, there was no statistically significant difference in accuracy of prediction for the four myopic categories. The two formulas are considered to be useful for high myopic cases.

Humans↗
PubMed1995

Dentatorubral-pallidoluysian atrophy (DRPLA). Molecular basis for wide clinical features of DRPLA.

Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder characterized clinically by various combinations of myoclonus, epilepsy, cerebellar ataxia, choreoathetosis, dementia and psychiatric symptoms. Based on the phenomenon of anticipation, the gene for DRPLA was recently identified. DRPLA is caused by unstable expansion of a CAG repeat in the gene located on the short arm of chromosome 12. As have been observed in Huntington's disease and SCA1, there is a strong correlation between the age of onset and the size of CAG repeats. Furthermore, patients with larger repeats tend to show a PME (progressive myoclonus epilepsy) phenotype as well as earlier ages of onset. More prominent anticipation and larger intergenerational increase of CAG repeats in paternal transmission can be accounted for by the meiotic instability of CAG repeats in male gametogenesis. Comparison of size distributions of CAG repeats in Japanese, African-American and white populations revealed that 7.4% of the Japanese alleles had greater than 19 repeats, whereas none of the whites and 1% of the African-American alleles were of this size. The results may account for the ethnic predilection of DRPLA.

Adult↗
PubMed1995

[A study of the intraorbital blood flow using ultrasound color Doppler mapping images in optic canal fracture cases].

Ultrasound color Doppler flow mapping image (CFMI) equipment, SSA-270A (Toshiba Co) was used to measure the blood flow velocity of the ophthalmic artery (OA) and the central retinal artery (CA) in eyes with optic canal fracture. The maximal blood flow velocity (V max), the minimal blood flow velocity (V min), the mean blood flow velocity (V mean), and the resistance index (RI) before and after transethmoidal decompression of the optic nerve were compared. The examination was conducted on 13 patients. There was no difference in blood flow velocity in the CA after the operation. Pre-operative V max and RI of the OA in the damaged eyes were lower than in normal eyes, but they increased the day after the operation. We measured the intraorbital blood flow velocity by CFMI because ultrasound does not penetrate bone. Since the peripheral artery from the optic foramen did not change after the operation, we concluded that the peripheral blood flow of OA had been quantitatively improved by the trans-ethmoidal decompression of the optic nerve.

Adolescent↗
PubMed1995

[Application of microdialysis for pharmacokinetic study in rabbit anterior chamber].

We evaluated a microdialysis technique for analyzing the pharmacokinetics of instilled or orally administered ofloxacin in the anterior chamber of pigmented rabbits. A microdialysis probe was inserted into the anterior chamber and was perfused (2 microliters/min) with Ringer solution using a microinjection pump. Two hours later, 20 microliters of 0.15 and 0.3% ofloxacin was instilled into an eye, or 20 mg/kg of the drug was administered into the stomach through an intubated catheter. Dialysate was then collected every 15 or 20 min for 6 (instillation) or 8 (oral administration) hours. Ofloxacin concentration in dialysates was determined with a HPLC-spectrofluorometry system. Ofloxacin levels in dialysates increased after the instillation in a dose-related manner, reached a maximum at 30 and 45 min, and then decreased gradually with t1/2 of 136 and 114 min after the 0.15% and 0.3% instillation, respectively. After oral administration, ofloxacin levels in dialysates reached a maximum at 120 min and decreased with t1/2 of 175 min. These data suggest the usefulness of microdialysis for pharmacokinetic studies in the anterior chamber, since continuous and stable data can be obtained from each animal.

Animals↗
PubMed1995

[A sporadic dentatorubral-pallidoluysian atrophy (DRPLA) diagnosed by gene analysis].

We report a 48-year-old woman with dentatorubral-pallidoluysian atrophy (DRPLA). She is the only patient in her 15 family members in two generations. She developed cerebellar ataxia and epilepsy at age 43. On admission at 48, she showed mild dementia and choreic movement in her face and extremities as well as truncal and limb ataxia. Routine laboratory examinations were normal. The point mutations in the tRNALys gene of mitochondrial DNA specific for MERRF were not found. A cranial CT scan and MRI showed mild atrophy of the cerebellum and prominent atrophy in the pons, especially in the tegmentum. Although she was thought to have DRPLA from the clinical point of view, absence of family history made the diagnosis difficult. Her parents were healthy until their 80's and died of cerebrovascular diseases and her 5 siblings had no symptoms. Hereditary DRPLA is known as an autosomal dominant disorder, with a high rate of penetrance and low rate of new mutation. According to our recent findings of a CAG repeat expansion in the DRPLA gene, this patient was diagnosed as a sporadic DRPLA. Considering the wide varieties of clinical manifestations, it is essential to examine this gene abnormality for diagnosing sporadic DRPLA.

Atrophy↗
PubMed1995

[Distribution of free amino acids and related compounds in ocular fluids of rat--I. Aging and inherited cataracts].

The distribution of free amino acids and their related compounds has been determined in the aqueous humors of Wistar strain and Ihara cataract f-strain (ICR) aging rats. Taurine was the most abundant amino acid in aqueous humors except in ICR rats of 16 and 70 weeks. It was supposed that the increase of serine and glutamine, and the decrease of aspartate, proline and glycine in aqueous humors were related to aging. There were interesting changes in amino acids related to opacity of lens, concentration of taurine was lower than that of Wistar rats in ICR rats of 4, 16, and 70 weeks, alanine and citrulline increased in Wistar rats and decreased in ICR rats, and histidine increased in ICR rats with aging. The changes in free amino acids in aqueous humors were the greatest in ICR rats, and these data will provide useful clues for the formation of cataract and the transportation of amino acids.

Aging↗
PubMed1995

[Intraocular lens power calculation for short eye].

The accuracy of intraocular lens power calculation formulas for short eyes was examined. We examined 217 eyes with an axial length of shorter than 22.5 mm, with postoperative visual acuity of 0. 5 or more, and postoperative astigmatism of less than +/- 2D. Five formulas were tested for accuracy in prediction for postoperative refraction, the S-SRK, the SRK, the SRK II, the SRK/T, and the Binkhorst formulas. The best results were produced by the S-SRK formula which predicted 74% of the cases within +/- 1D error, if the axial length was shorter than 22 mm. The A-constant was also examined to study the effect of postoperative refraction. The A-constant takes into consideration the depth of the anterior chamber lens, so that the differences in depth would be influenced for short eyes rather than regular eyes in prediction. However, there was no significant difference among the different A-constant groups.

Cataract Extraction↗
PubMed1994

Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA).

Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurologic disorder characterized by variable combinations of myoclonus, epilepsy, cerebellar ataxia, choreoathetosis and dementia. By specifically searching published brain cDNA sequences for the presence of CAG repeats we identified unstable expansion of a CAG in a gene on chromosome 12 in all the 22 DRPLA patients examined. A good correlation between the size of the CAG repeat expansion and the ages of disease onset is found in this group. Patients with earlier onset tended to have a phenotype of progressive myoclonus epilepsy and larger expansions. We propose that the wide variety of clinical manifestations of DRPLA can now be explained by the variable unstable expansion of the CAG repeat.

Adolescent↗