Search PubMed⌕ Search

Biomedical subjects

N Yasui

Publications and source records attributed to N Yasui.

At least 91 records · Page 5Linked to original sources
PubMed1998

p53 tumor suppressor gene in acoustic neuromas.

Alterations of the p53 tumor suppressor gene in 21 cases with acoustic neuroma were investigated by polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) and single strand conformation polymorphism (PCR-SSCP). Neither mutation nor deletion was found. In 13 informative cases, no loss of heterozygosity (LOH) was confirmed. Thus our results further substantiate the scant contribution of p53 gene tumorigenesis and cell proliferation to acoustic neuromas.

Genes, p53↗
PubMed1998

Significance of hearing preservation in acoustic neuroma surgery.

In the past 10 years, 43 patients with acoustic neuroma have been operated on by the middle cranial fossa approach. In all cases, meticulous care was taken to preserve the cochlear function regardless of the degree of preoperative hearing disorder. Thirty-nine of 43 patients had various degrees of residual hearing, hearing was preserved in 16 of these (41%). The best result was obtained in patients with a tumor located less than 1 cm from the porus. The hearing preservation rate was 64% (11/17). The patients recovered hearing acuity quite well, especially at low frequencies in 2 cases who had a pure tone hearing level of more than 50 dB and less than 50% of speech discrimination. These 2 cases had a history of sudden deafness that was intractable 5 months preoperatively. Thus it is not correct to set certain criteria for hearing preservation for patients whose preoperative hearing may not be serviceable.

Audiometry↗
PubMed1998

Single oral dose kinetics of zotepine and its relationship to prolactin response and side effects.

The authors investigated the single oral dose kinetics of zotepine and its relationship with prolactin response and side effects in 14 healthy male volunteers. Each subject took a single oral 25-mg dose of zotepine, and plasma concentrations of zotepine, prolactin, and their side effects were monitored up to 36 hours after dosing. The means +/- SD of the time of maximal plasma concentration (tmax), the apparent oral clearance, the apparent volume of distribution, and the elimination half-life (t1/2) were 3.8 +/- 1.2 hours, 4.6 +/- 4.2 1/h.kg, 109.0 +/- 59.0 1/kg, and 21.0 +/- 8.9 hours, respectively. The change in prolactin concentrations and side effect scores were parallel with that of drug concentrations, although no significant correlation was found between these three parameters at any time-point. The current results clearly indicate that the tmax and t1/2 of zotepine are much longer than those previously reported, which are reflected in the changes in prolactin concentrations and side effect scores.

Administration, Oral↗
PubMed1998

Anticipation in familial cavernous angioma: ascertainment bias or genetic cause.

OBJECTIVES: Anticipation has been linked to unstable trinucleotide repeats in many neurological disorders. We examined the hypothesis of genetic anticipation in familial cavernous angioma (FCA) of the central nervous system. MATERIAL AND METHODS: The mean ASO of affected individuals was compared between successive generations in 55 families. Intergenerational pair-wise comparisons were employed to avoid several ascertainment biases. Regarding severity of disease both type of manifestation and number of cavernous angiomas were compared between generations. RESULTS: The mean ASO decreased significantly both from the first to the second generation (31.6 vs 17.8 years; P = 0.000) and from the second to the third generation (17.8 vs 6.7 years; P = 0.002). The pair-wise comparisons also showed significantly earlier ASO. No clear evidence for anticipation with regard to severity of disease was found. CONCLUSIONS: Molecular genetic studies will determine whether trinucleotide repeats are the underlying mechanism for our observation of anticipation in FCA.

Adolescent↗
PubMed1998

Prolactin response to bromperidol treatment in schizophrenic patients.

The prolactin response to an antipsychotic drug, bromperidol was studied in 24 schizophrenic in-patients (13 males. 11 females). Eight patients were given 6 mg/day, 8 were given 18 mg/day. Duration of treatment was 3 weeks. Plasma concentrations of bromperidol and reduced bromperidol were measured by high-performance liquid chromatography, and that of prolactin was measured by radioimmunoassay. Bromperidol treatment significantly (P < 0.01) increased plasma concentration of prolactin each week. The mean +/- S.D. of the delta-prolactin (the mean concentration during treatment minus the pretreatment concentration) was 13.3 +/- 12.4 ng/ml. Multiple regression analysis showed that the delta-prolactin concentration was significantly greater in females than in males (P < 0.05) and correlated to plasma concentrations of bromperidol (P < 0.001) and reduced bromperidol (P < 0.0001). These results suggest that the prolactin response to bromperidol treatment depend on plasma concentrations of both bromperidol and reduced bromperidol and gender, and that reduced bromperidol is involved in the pharmacological effects during bromperidol treatment.

Adult↗
PubMed1998

Analysis of localization of mutated tissue-nonspecific alkaline phosphatase proteins associated with neonatal hypophosphatasia using green fluorescent protein chimeras.

Hypophosphatasia is associated with a defect of the tissue-nonspecific alkaline phosphatase (TNSALP) gene. The onset and clinical severity are usually correlated in hypophosphatasia; patients with perinatal hypophosphatasia die approximately at the time of birth. In contrast, we describe a male neonatal patient with hypophosphatasia who had no respiratory problems and survived. He was compound heterozygous for the conversion of Phe to Leu at codon 310 (F310L) and the deletion of a nucleotide T at 1735 (delT1735), causing the frame shift with the result of the addition of 80 amino acids at the C-terminal of the protein. Because the C-terminal portion of TNSALP is known to be important for TNSALP to bind to the plasma membrane, the localization of wild-type and mutated TNSALP proteins was analyzed using green fluorescent protein chimeras. The expression vectors containing the complementary DNA of fusion proteins consisting of signal peptide, green fluorescent protein, and wild-type or mutated TNSALP, caused by delT1735 or F310L mutation, were introduced transiently or stably in Saos-2 cells. The delT1735 mutant failed to localize at the cell surface membrane, whereas the wild-type and the F310L mutants were located in the plasma membrane and cytoplasm. The assay for enzymatic activity of TNSALP revealed that the delT1735 mutant lost the activity and that the F310L mutant exhibited an enzymatic activity level that was 72% of the normal level. The F310L mutation was also detected in another neonatal patient with relatively mild (nonlethal) hypophosphatasia (reported in J Clin Endocrinol Metab, 81:4458-4461, 1996), suggesting that residual ALP activity of the F310L mutant contributes to the less severe phenotype. The patient is unique, with respect to a discrepancy between onset and clinical severity in hypophosphatasia.

Alkaline Phosphatase↗
PubMed1998

Residual deformity in congenital radial club hands after previous centralisation of the wrist. Ulnar lengthening and correction by the Ilizarov method.

We used the Ilizarov method in seven patients with severe congenital radial club hands who had had previous wrist surgery, to correct residual shortening and bowing of the ulna together with recurrent wrist deformity. The mean age at operation was 6.5 years. The mean ulnar shortening was 5.3 cm and the mean angular deformity 42 degrees. The mean length gained was 51% of the original ulna. The mean healing index was 46.9 days (29.8 to 64.0). The ratio of the length of the lengthened ulna to the normal side improved on average from 64% to 95%. The angular deformity was initially completely corrected in six out of seven patients. The length ratio, however, decreased to 83% at the final follow-up. In four patients, the angular deformity partially recurred. We recommend correction of congenital radial club hand by staged procedures. The first is centralisation and stabilisation of the wrist and the second lengthening of the ulna and correction of the angular deformity using the Ilizarov method.

Bone Lengthening↗
PubMed1998

Genotype phenotype correlation in achondroplasia and hypochondroplasia.

Recent studies of the fibroblast growth factor receptor 3 (FGFR3) gene have established that achondroplasia and hypochondroplasia are allelic disorders of different mutations. To determine whether the genotype could be distinguished on the basis of the phenotype, we analysed height, arm span, and skeletal radiographs from 23 patients with achondroplasia and the G380R mutation of FGFR3 and eight with hypochondroplasia and the N540K mutation. Both conditions share the classical pathological features of micromelic short stature, reduced or unchanged interpedicular distances in the lumbar spine, disproportionately long fibulae, and squared and shortened pelvic ilia. These were significantly more severe in the G380R patients than in the N540K patients. Our findings have shown a firm statistical correlation between the genotype and the phenotype, although there were a few exceptional cases in which there was phenotypic overlap between the two conditions.

Achondroplasia↗
PubMed1998

Impaired expression of noncollagenous bone matrix protein mRNAs during fracture healing in ascorbic acid-deficient rats.

In scorbutic patients, fractures are slow to heal because of impaired collagen synthesis. To investigate the influence of impaired collagen synthesis on the differentiation and proliferation of osteogenic and chondrogenic cells, we examined the expression of genes encoding bone matrix proteins, including osteonectin (ON), osteopontin (OPN), osteocalcin (OC), and matrix Gla protein (MGP), as differentiation markers for osteogenic and chondrogenic cells during fracture healing in Osteogenic Disorder Shionogi (ODS) rats, which have a hereditary defect in the ability to synthesize ascorbic acid (Asc). In ODS rats without Asc supplementation, intramembranous ossification was completely inhibited. Although a few fibroblast-like cells expressing ON mRNA were observed, no OPN mRNA-expressing cells were detected. During endochondral ossification, a small amount of metachromatic staining cartilage appeared at the fracture site, but there was no provisional calcification zone in the cartilage. Chondrocytes expressed ON and MGP mRNAs, but not OPN mRNA. When Asc was given to these rats, callus formation was soon detected around the fracture site, while OPN mRNA was expressed by differentiated osteoblasts and hypertrophic chondrocytes. Our data indicate that impaired collagen synthesis due to Asc deficiency inhibited the increase of ON and MGP mRNA-expressing cells as well as the appearance of OPN mRNA-expressing cells. Since OPN is considered to play an important role in normal and pathological mineralization, lack of OPN mRNA expression accompanying impaired collagen synthesis may have a role in defective mineralization and delayed fracture healing in scurvy.

Animals↗
PubMed1998

Expression of bone matrix proteins mRNA during distraction osteogenesis.

Distraction osteogenesis is a recently advanced principle of bone lengthening in which a bone separated by osteotomy is subjected to slow progressive distraction using an external fixation device. Appropriate mechanical tension-stress is believed not to break the callus but rather to stimulate osteogenesis. To study the molecular features of this process, the expression and localization of the mRNAs encoding osteopontin (OPN), osteocalcin (OC), matrix Gla protein (MGP), osteonectin (ON), and collagen type I and I during distraction osteogenesis were examined by in situ hybridization and Northern blot analysis. The process can be divided into three distinct phases: the lag phase for 7 days between osteotomy and the beginning of distraction, the distraction phase for 21 days, and the consolidation phase for several weeks. The histologic and molecular events taking place during the lag phase were similar to those observed in fracture healing. The osteotomy site was surrounded by external callus consisting of hyaline cartilage. As distraction started at the rate of 0.25 mm/12 h, the cartilaginous callus was elongated, deformed, and eventually separated into proximal and distal segments. The chondrocytes were stretched along the tension vector and became fibroblast-like in shape. Although morphologically these cells were distinguishable from osteogenic cells, they expressed OPN, OC, and alkaline phosphatase mRNAs. As distraction advanced, the cartilaginous callus was progressively replaced by bony callus by endochondral ossification and thereafter new bone was formed directly by intramembranous ossification. OPN mRNA was detected in preosteoblasts and osteoblasts at the boundary between fibrous tissue and new bone. ON, MGP, and OC mRNAs appeared early in the differentiation stage. The variety of cell types expressing mRNA encoding bone matrix proteins in distraction osteogenesis was much greater than that detected in the embryonic bone formation and fracture healing process. Moreover, the levels of OPN, ON, MGP, and OC mRNA expression markedly increased during the distraction phase. These results suggested that mechanical tension-stress modulates cell shape and phenotype, and stimulates the expression of the mRNA for bone matrix proteins.

Animals↗
PubMed1998

Effects of treatment with nilvadipine on cerebral ischemia in rats.

The protective effects of a Ca2+ antagonist, nilvadipine, on focal cerebral ischemia were studied in male spontaneously hypertensive rats. The animals received either nilvadipine (3mg x kg(-1) x day(-1)) or a vehicle subcutaneously. Group 1 (n=11) was treated for 7 days, and Group 2 (n=11) for 14 days. The middle cerebral artery was occluded on the 6th (Group 1) or 13th (Group 2) day of the treatment, and neuropathological outcomes were quantified 24 hours later. The mean arterial blood pressure was significantly reduced with nilvadipine to normal levels. The % infarct volumes of Groups 1 (37+/-2) and 2 (34+/-3) were significantly less than those of their controls (39+/-3 [n=11] and 40+/-4 [n=12], respectively), although the difference between Groups 1 and 2 was not significant. When infarct areas were compared in each of 8 coronal sections, the infarct size had decreased in the 5 posterior sections in Group 2, but only in 2 sections of Group 1. A significant decrease in the edema volumes was observed in Group 2, but not in Group 1. Thus, nilvadipine provided protective effects against cerebral ischemia in rats having chronic hypertension, and the effects were dependent on the duration of treatment.

Animals↗
PubMed1998

Arterial occlusive lesions following wrapping and coating of unruptured aneurysms.

Seven patients (mean age 57 years) developed arterial occlusive lesions following both wrapping and coating during surgery for unruptured aneurysms. Five patients had no risk factors for arteriosclerosis, and two had hypertension or diabetes mellitus. The aneurysms were located in the middle cerebral artery in four cases, and the internal carotid artery in three. Both 100%-cellulose cotton (Bemsheet) and cyanoacrylate glue (Biobond) were used as reinforcement materials. Postoperative angiography revealed complete clipping, and no parent artery stenoses, although one patient had a non-symptomatic diffuse narrowing in the entire carotid fork 7 days following surgery. Three patients had progressive stroke 4-5 weeks following surgery, and two had no symptoms. Both reinforcement materials were used as little as necessary in the last two patients, but they had either transient ischemic attacks or progressive stroke 2 months following surgery. Arterial steno-occlusion was confirmed angiographically in all patients. These vascular lesions were probably induced by both direct toxicity of the cyanoacrylate glue and fibrosis or granuloma formation caused by the cotton fibers. The observed angiographical reversibility suggests that the cyanoacrylate glue is more likely to be the cause of the lesions than the cotton fibers.

Aged↗
PubMed1998

Effects of dobutamine on brain surface microvessels in rats.

The effects of dobutamine on the diameters of rat pial vessels were investigated in vivo using a closed cranial window technique. Dobutamine (10(-7)-10(-3) M) was dissolved in artificial cerebrospinal fluid (CSF). Arterioles (17-78 microns in diameter) and venules (20-97 microns in diameter) were observed through the cranial window over the left parietal cortex. Superfusion of the brain surface with only artificial CSF had no effect on vessel diameter. Dobutamine, even at a high concentration of 10(-4) M, did not induce significant diameter changes in the pial vessels, compared with control animals. The arterioles showed marked dilatation (+73%) during superfusion with 10(-3) M dobutamine (p < 0.01 vs. control). The venules were also dilated (+12%), although the increased diameter was not statistically different from controls. Therefore, dobutamine did not induce a dose-dependent dilation. The results strongly suggest that dobutamine at clinical dosages does not have a direct vasomotor effect on brain microvessels.

Animals↗
PubMed1998

[Japan Coma Scale as a grading scale of subarachnoid hemorrhage: a way to determine the scale].

BACKGROUND: The grading scale for subarachnoid hemorrhage (SAH) with inter-grade outcome differences is essential for evaluating the effectiveness of newly developed therapeutic modalities. Although Hunt's grade and WFNS scale have been widely used, these grading scales do not meet this requirement. We previously proposed a revised WFNS scale based solely on the Glasgow Coma Scale (GCS) that has intergrade outcome differences of high-level significance. The Japan Coma Scale (JCS) has been long and widely used in Japan. The purpose of this study is to show whether it is possible to determine a reasonable SAH grading scale based on the JCS and to show a way to determine an SAH grading scale. PATIENTS AND METHODS: We retrospectively analyzed 1398 consecutive cases of aneurysmal SAH operated on within Day 7 of the latest onset. The preoperative JCS and GCS were evaluated just before the surgery and the Glasgow Outcome Scale (GOS), analyzed with numerical transformation (1 = dead to 5 = good recovery), was estimated at 6 months after the onset. All 510 possible combinations of scores of JCS were statistically tested under the following 2 assumptions; (1) JCS = 0 and JCS = 100 fall into a single independent grade. (2) No other single JCS score should fall into a single grade. RESULTS: The outcome differences between JCS 0 and 1, and 100 and 200 are significant. The outcome difference between JCS 30 and 100 is relatively higher than any other set of 2 scores of JCS. Only 5 combinations are practical among the candidates to be analyzed. Out of 510 combinations, the following combination shows the highest inter-grade outcome differences; I (JCS = 0, n = 375, mean GOS = 4.78) II (JCS = 1, 2; n = 310; mean GOS = 4.47) III (JCS = 3-30; n = 476; mean GOS = 3.96) IV (JCS = 100; n = 96; mean GOS = 3.10) V (JCS = 200, 300; n = 141; mean GOS = 2.33). In JCS, the mean outcome of JCS = 3 is worse than those of JCS = 10, 20, and 30. The outcome difference between JCS 0 and 1 is only significant in patients over 60 years old. CONCLUSION: Taking all the 510 possible combinations of JCS into consideration, we obtained a reasonable combination containing 5 grades. Although this grading scale showed good inter-grade outcome differences, JCS is not preferable to GCS as a consciousness evaluation system in the acute phase of SAH. We emphasize the importance of this way to determine a grading scale with a combinatorial approach, which can be applicable for re-evaluating the grading scales in the future.

Age Factors↗
PubMed1997

Relationship between the CYP2D6 genotype and the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine.

The relationship between the cytochrome P450 (CYP) 2D6 genotype and the steady-state plasma concentrations (Css) of trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) was studied in 54 depressed Japanese patients receiving trazodone 150 mg at bedtime. By use of allele-specific PCR analysis, the wild type allele, three mutated alleles causing absent enzyme activity (CYP2D6A, CYP2D6B and CYP2D6D) and one mutated allele causing decreased enzyme activity (CYPZD6 Ch) were identified. The means (ranges) of the Css of trazodone, corrected to the median body weight in 17 cases with no mutated allele, 27 cases with one mutated allele and 10 cases with two mutated alleles, were 556 (281-1115), 643 (302-1362) and 671 (234-1418) ng/ml, respectively, while the values of mCPP were 60 (35-121), 65 (33-99) and 58 (38-112) ng/ml, respectively. Neither the Css of trazodone (F = 0.80, P = 0.45) nor that of mCPP (F = 0.49, P = 0.61) significantly differed among the three groups. The present study thus suggests that the CYP2D6 genotype cannot predict the Css of these compounds.

Adult↗
PubMed1997

Interaction between carbamazepine and bromperidol.

OBJECTIVE: The interaction between carbamazepine and bromperidol was studied in 13 schizophrenic inpatients. METHODS: Before carbamazepine addition, the subjects were taking bromperidol 12-24 mg.day-1 for 1-20 weeks. Carbamazepine 400 mg.day-1 was coadministered for 4 weeks, and blood samplings were performed before carbamazepine addition and at weekly intervals after the addition. Plasma concentrations of bromperidol and its reduced metabolite were measured by high-performance liquid chromatography. RESULTS: Carbamazepine significantly decreased plasma concentrations of both bromperidol and reduced bromperidol for all weeks. On average, the plasma concentrations of bromperidol and reduced bromperidol at 4 weeks were 37% and 23% of the corresponding precarbamazepine values. Despite these decreases in plasma concentration, the Clinical Global Impression scores decreased slightly but significantly after carbamazepine addition. CONCLUSION: The present study suggests that carbamazepine decreases plasma concentrations of bromperidol and its reduced metabolite by inducing the metabolism of these compounds. Nevertheless, adjunctive carbamazepine may be useful for schizophrenic patients treated with bromperidol.

Adult↗