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Biomedical subjects

N Yasui

Publications and source records attributed to N Yasui.

At least 127 records · Page 7Linked to original sources

Lengthening of the lower limbs in patients with achondroplasia and hypochondroplasia.

Ten years of experience in lower limb lengthening achieved in 35 patients with achondroplasia and seven patients with hypochondroplasia is reported. A uniform method of callus distraction (callotasis) was used in all cases, although the order of lengthening of each bone differed among the cases. The mean age of the patients at the time of first operation was 14.5 years; at followup, the mean age was 18.8 years. The mean lengthening achieved in the femur was 7.2 cm (range, 4.5-12 cm) and in the tibia 7.1 cm (range, 4.5-13 cm). More lengthening was achieved in the more recent cases. The function of lengthened limbs, evaluated by physical strength tests, was better at followup than before lengthening in the growing children, although the mechanical axes of the lengthened bones were not necessarily in correct alignment.

Achilles Tendon↗

Tumor growth and metastasis of human colorectal cancer cell lines in SCID mice resemble clinical metastatic behaviors.

Ten human colorectal cancer (CRC) cell lines were implanted orthotopically into the ceca and also into the livers, muscles and peritoneal cavities of SCID mice in order to analyze the characteristics regulating metastatic behaviors of CRCs. All the CRC cell lines formed tumors in the muscle and cecum, but they could be classified into two groups: (1) six cell lines with high tumorigenicity in the liver (HTLs) forming differentiated tumors, and (2) four with no tumorigenicity in the liver (NTLs) forming poorly differentiated tumors in SCID mice. After orthotopic implantation, NTLs never metastasized to the liver, whereas HTLs did. Therefore, intrahepatic tumorigenicity and differential status were closely associated with liver metastasis whereas differentiation was not associated with lung metastasis. The 6 HTLs demonstrated an inverse correlation between liver metastases and peritoneal dissemination, and immunohistochemistry indicated expression of sLeX, CA19-9 and carcinoembryonic antigen in tumors which correlated well with the liver metastatic rate. We found a strong correlation between liver metastasis and intrahepatic tumorigenicity and could reproduce the clinical correlations between the pattern of the metastatic spread and the differentiation phenotype of CRC in vivo. We consider further examination using this model will be useful for analyzing the complex mechanisms involved in clinically metastasizing CRCs.

Adenocarcinoma↗

Human brain tumor O(6)-methylguanine-DNA methyltransferase mRNA and its significance as an indicator of selective chloroethylnitrosourea chemotherapy.

O(6)-methylguanine-DNA methyltransferase (MGMT) removes and repairs chloroethylnitrosourea (CENU)-induced O(6)-methylguanine-DNA by accepting the alkyl group at a cysteine moiety. MGMT activity is, therefore, predictive of resistance or sensitivity to CENU chemotherapy. We measured the levels of MGMT mRNA expression in human brain tumors using a reverse transcription-polymerase chain reaction (RT-PCR) method, and studied the significance of MGMT mRNA levels in CENU chemotherapy. The level of MGMT mRNA was represented as a percentage relative to the MGMT mRNA in U138MG brain tumor cells. Forty-three patients with brain tumors were entered into the study. High-grade gliomas had significantly lower levels of MGMT mRNA than did low-grade gliomas and non-glial tumors (p < 0.05 determined by analysis of covariance). Out of 14 high-grade gliomas, 4 had a level of MGMT mRNA below 10%, indicating chemosensitivity to CENU. Out of 11 patients who received CENU chemotherapy, 3 had a partial response. All 3 responders had a low level of MGMT mRNA. The time to tumor progression (TTP) for 6 patients with a level lower than the median was short, but significantly longer than the TTP for 5 patients with a higher level (p < 0.05 determined by Gehan's Wilcoxon test). These results indicate that a fraction of brain tumors have a low expression of MGMT mRNA, and that the level of MGMT mRNA is a useful indicator of effectiveness in selective CENU chemotherapy.

Antineoplastic Agents, Alkylating↗

Functional localization of sensorimotor cortex by somatosensory evoked potentials produced by femoral nerve stimulation.

Cortical somatosensory evoked potentials (SSEPs) can be used to localize the central sulcus during a craniotomy. In particular, contralateral median nerve stimulation producing SSEPs can disclose the location of the central sulcus around the sensorimotor hand representation area. However, the median nerve cannot be stimulated in patients who undergo craniotomy at locations other than the hand representation area. The present study attempts to localize the central sulcus in the lateral surface of the brain near the interhemispheric fissure by stimulating the contralateral femoral nerve to produce SSEPs. Somatosensory evoked potentials were recorded between the superior lip of the interhemispheric fissure and 1.5 to 2 cm laterally in the cortex. Only seven of the 12 patients studied showed a phase reversal of the initial component across the central sulcus. The polarity was negative in the postcentral gyrus and positive in the precentral gyrus. The other five patients did not show a phase reversal of the initial component across the central sulcus. The amplitude was highest in the postcentral gyrus and the polarity was positive. Based on these results, the authors hypothesize that stimulating the contralateral femoral nerve to produce SSEPs and then analyzing the distribution of the SSEPs may provide a method for functional localization of the sensorimotor cortex around the interhemispheric fissure during craniotomy.

Journal Article↗

Dominant negative inhibition of the association between beta-catenin and c-erbB-2 by N-terminally deleted beta-catenin suppresses the invasion and metastasis of cancer cells.

Aberrant tyrosine phosphorylation of beta-catenin inactivates the E-cadherin-mediated cell adhesion and invasion suppressor system in cancer cells. Elucidation of the association between beta-catenin and c-erbB-2 protein prompted us to investigate whether interference with this interaction can change the invasive phenotype. In a human gastric cancer cell line, TMK-1, N-terminally deleted beta-catenin, which binds to c-erbB-2 but not to cadherin, inhibited the association between endogenous beta-catenin and c-erbB-2 protein, and suppressed the tyrosine phosphorylation of beta-catenin. Cells expressing truncated beta-catenin exhibited markedly reduced invasiveness in vitro and peritoneal metastasis in vivo, and developed an epithelial morphology. These results suggest that tyrosine phosphorylation of beta-catenin regulated by c-erbB-2 protein may play an important role in the invasion, metastasis and morphogenesis of cancer cells and that inhibition of the aberrant tyrosine phosphorylation of beta-catenin effectively prevents invasion and metastasis of cancer cells.

Animals↗

Quantitative evaluation of neutral amino acid transport in cerebral gliomas using positron emission tomography and fluorine-18 fluorophenylalanine.

To elucidate the mechanism of large neutral amino acid (LNAA) transport in cerebral gliomas and to evaluate the clinical usefulness of positron emission tomography (PET) with fluorine-18 fluorophenylalanine (18F-Phe), we examined 18 patients with cerebral glioma using dynamic PET and 18F-Phe. By employing two-compartment model analysis, the influx rate K1, the efflux rate k2 and the distribution volume (Vd) of 18F-Phe were estimated in tumour tissue and contralateral normal grey matter. 18F-Phe showed increased accumulation in tumour tissue regardless of the grade of malignancy in all patients. The rate of uptake of 18F-Phe in high-grade glioma was significantly higher than in low-grade glioma (P <0.05). However, it was difficult to evaluate the tumour grade only from the 18F-Phe accumulation in individual cases. Values of K1 and Vd were significantly increased in the tumour tissue. The K1 value of the tumour tissue tended to decrease with increasing LNAA concentration in plasma. Therefore, influx of 18F-Phe into tumour tissue is mainly related to the carrier-mediated active transport. It is concluded that PET with 18F-Phe is of clinical value for tumour detection rather than assessment of tumour malignancy.

Amino Acids↗

New display methods of combined topographic EEG and cerebral blood flow images in the evaluation of cerebral ischemia.

To evaluate complicated changes in the EEG and cerebral blood flow (CBF) in cerebral infarction, EEG was recorded under various blood pressure levels, during CBF measurement with positron emission tomography, in patients with chronic cerebral infarction. Newly developed display methods which combine topographic EEG and its significance probability mapping with CBF, clearly provided objective measures of changes in EEG parameters and CBF, during induced hypo- and hypertension.

Aged↗

A recurrent 1992delCT mutation of the type X collagen gene in a Japanese patient with Schmid metaphyseal chondrodysplasia.

We report here a recurrent frameshift mutation within the carboxyl-terminal noncollagenous domain coding region of the type X collagen gene (COL10A1) in a Japanese patient with Schmid metaphyseal chondrodysplasia. The mutation involves deletion of a CT dinucleotide from position 1992 (1992delCT), and produces a frameshift which creates a premature termination codon close to the site of the deletion. The predicted length of the mutant polypeptide is 664 amino acids, which is shorter than the wild type polypeptide (680 amino acids). A 1992delCT mutation of COL10A1 has been previously reported in one family. The independent occurrence of de novo mutation of this specific dinucleotide repeat suggests that this region is a possible mutational hot spot on COL10A1.

Asian People↗

A kinetic and dynamic study of oral alprazolam with and without erythromycin in humans: in vivo evidence for the involvement of CYP3A4 in alprazolam metabolism.

OBJECTIVE: To assess the possible involvement of CYP3A4 in the metabolism of alprazolam in vivo. METHOD: Twelve healthy male volunteers were randomly allocated to one of the two different treatment sequences, placebo-erythromycin or erythromycin-placebo, with an at least 6-week washout period between the two trial phases. Each volunteer received 400 mg erythromycin or matched placebo given orally three times a day for 10 days and an oral dose (0.8 mg) of alprazolam on the posttreatment day 8. Plasma concentration of alprazolam was measured up to 48 hours after the administration, and psychomotor function was assessed at each time of blood samplings with use of the Digit Symbol Substitution Test, visual analog scale, and Udvalg for kliniske undersøgelser side effect rating scale. RESULTS: Erythromycin significantly (p < 0.001) increased the area under the plasma concentration-time curves (200 +/- 43 versus 322 +/- 49 ng . hr/ml from 0 to 48 hours and 229 +/- 52 versus 566 +/- 161 ng . hr/ml from 0 hour to infinity), decreased the apparent oral clearance (1.02 +/- 0.31 versus 0.41 +/- 0.12 ml/min/kg), and prolonged the elimination half-life (16.0 +/- 4.5 versus 40.3 +/- 14.4 hours) of alprazolam. However, any psychomotor function variables did not differ significantly between the erythromycin and placebo trial phases. CONCLUSION: This study suggests that erythromycin, an inhibitor of CYP3A4, inhibits the metabolism of alprazolam, providing an in vivo evidence for the involvement of CYP3A4 in its metabolism. However, the kinetic change of alprazolam by erythromycin does not result in the pharmacodynamic change of this triazolobenzodiazepine, at least after single dosing.

Administration, Oral↗

No interaction between desipramine and bromperidol.

1. The authors studied the effects of coadministration of desipramine, which is a substrate of CYP2D6, on plasma concentrations of bromperidol and its reduced metabolite (reduced bromperidol). Clinical changes were also evaluated by the CGI and UKU. 2. The subjects were 13 schizophrenic inpatients receiving bromperidol 12.24 mg/day for 1.20 weeks. Desipramine 50 mg/day was coadministered for 1 week, and blood samplings and clinical ratings were performed before and after the coadministration. 3. Plasma concentrations of bromperidol and reduced bromperidol were measured by a HPLC method. 4. Desipramine coadministration did not affect plasma concentration of bromperidol (9.6 +/- 4.5 vs. 9.6 +/- 2.8 ng/ml) nor that of reduced bromperidol (2.8 +/- 2.5 vs. 2.8 +/- 2.1 ng/ml). 5. There was no significant change in the CGI scores nor UKU scores after desipramine coadministration. 6. The present study thus suggests that there is no interaction between desipramine and bromperidol.

Adult↗

Plasma prolactin concentration and psychopathology of schizophrenia.

1. The correlation between plasma prolactin concentration and psychopathology, as assessed by the BPRS, was studied in 56 unmedicated schizophrenic patients (28 males, 28 females). 2. There was no significant correlation between plasma prolactin concentration and total BPRS score or each item score. 3. No significant correlation was found when the BPRS items were classified into five clusters, i.e., positive, excitement, cognitive, negative, and anxiety-depression symptoms. 4. When males and females were analyzed separately, no significant correlation was found except a weak negative correlation (rs = -0.388, p < 0.05) for hostility score in females. 5. The present study suggests that plasma prolactin concentration does not reflect psychopathology of schizophrenia.

Adolescent↗

Carbamazepine augmentation therapy in three patients with trazodone-resistant unipolar depression.

In three patients with trazodone-resistant unipolar depression, carbamazepine 400 mg/day was co-administered for 4 weeks. They all showed favourable responses; two non-delusional patients completely or almost recovered, while one delusional patient showed considerable improvement in depressive symptoms other than delusions of guilt. Plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) were decreased, while the m-CPP/trazodone ratio was increased in all cases. The present report suggests that carbamazepine augments antidepressant effects of trazodone by an enhancement of serotonin function.

Aged↗

Anosmia after anterior communicating artery aneurysm surgery: comparison between the anterior interhemispheric and basal interhemispheric approaches.

The olfactory function could be examined in 101 of 138 patients with anterior communicating artery aneurysms, whom we treated during a recent 6-year period. Among them, 49 patients underwent surgery by the anterior interhemispheric approach and 52 underwent surgery by the basal interhemispheric approach. Fifteen patients (31%) exhibited anosmia after surgery by the anterior interhemispheric approach, whereas only one patient (1.9%) exhibited anosmia after surgery by the basal interhemispheric approach. Unilateral dural incision and unilateral brain retraction without elevation of the frontal lobe from the frontal base are important, because frontal lobe depression and elevation during surgery may injure the olfactory nerve.

Adult↗

Anatomic study of anterior frontal cortical bridging veins with special reference to the frontopolar vein.

Anatomic variations of the frontopolar vein were investigated in 21 cadaver brains to improve the preservation rate of this vein in interhemispheric surgery for anterior communicating aneurysms. Most of the frontopolar vein has been considered to drain the outer convex side of the frontal lobe, but in reality, the area of its venous drainage was found to cover a large part of the frontal lobe, including its medial and basal surfaces. This observation suggests that sacrifice of the vein during surgery carries a risk of venous infarction. Therefore, care must be taken to not injure the vein during surgery. The mean distance between the frontopolar vein and the most anterior point of the frontal lobe was 31.1 mm. Although the vein became smaller close to the frontal tip, the mean diameter of the vein was 1.9 mm. Morphologically, approximately two-thirds of the frontopolar veins was found to have a "main trunk." The frontopolar vein can be spared during surgery by using a flexible surgical technique incorporating vein dissection or additional craniotomy.

Aged↗

Glasgow Coma Scale in the prediction of outcome after early aneurysm surgery.

OBJECTIVE: A prospective study was performed to analyze whether the Glasgow Coma Scale (GCS) was useful in predicting the outcome after early surgical intervention for aneurysmal subarachnoid hemorrhage (SAH). METHODS: In a consecutive series of 765 patients who underwent surgery for aneurysms within 7 days after SAH, the level of consciousness was assessed by the GCS just before surgery and the outcome was graded by the Glasgow Outcome Scale 6 months after surgery. RESULTS: The patient distribution in accordance with the GCS sum scores in descending order from 15 to 3 was as follows: 334, 140, 58, 27, 20, 26, 27, 19, 26, 17, 20, 27, and 24 patients, respectively. In general, the higher the preoperative GCS score was, the better the surgical outcome was. The overall surgical result was significantly correlated with the preoperative GCS score (rs = 0.615, P < 0.001). With respect to the levels that distinguish the outcome along the GCS axis, a significant difference in the outcome was observed only between the GCS scores of 15 and 14 (P < 0.001, Wilcoxon test). CONCLUSION: The GCS proved useful in the preoperative evaluation of patients with SAH, in terms of outcome prediction. It is suggested that the SAH scale proposed by the World Federation of Neurosurgical Societies be reexamined, because differences in outcomes were not clear between the GCS scores of 13 and 12 or between those of 7 and 6, in which Grades III and IV and Grades IV and V are differentiated in the scale, respectively.

Adult↗

Subarachnoid hemorrhage caused by previously diagnosed, previously unruptured intracranial aneurysms: a retrospective analysis of 25 cases.

OBJECTIVE: We conducted a retrospective analysis of the clinical features of angiographically diagnosed unruptured intracranial aneurysms that were treated conservatively and subsequently ruptured. METHODS: At our center, we reviewed the angiographic and clinical features of 25 patients with subarachnoid hemorrhage caused by previously unruptured aneurysms. RESULTS: Eleven of the 25 patients died, including 1 patient who had undergone surgery. Ten patients had single aneurysms, and 15 had multiple aneurysms. Thus, multiple aneurysms were significantly more common than single aneurysms. The associated disease was cerebral infarction in 12 patients, previous subarachnoid hemorrhage from different aneurysm in 8 patients, intracerebral hemorrhage in 3 patients, and other conditions in 2 patients. Aneurysm size was able to be evaluated after rupture in 20 patients. At initial diagnosis, 16 aneurysms measured less than 5 mm in maximum diameter; the size of most aneurysms had increased by the time of rupture, although the aneurysm size remained less than 5 mm in five patients. No relationship was found between aneurysm rupture and patient age, aneurysm size at initial diagnosis, or time interval from diagnosis to rupture. The incidence of aneurysm rupture in patients with cerebrovascular disease, although higher than the incidence in patients with other underlying disease, was not significant. CONCLUSION: We conclude that small unruptured intracranial aneurysms measuring less than 5 mm are susceptible to the risk of rupture, so that radical treatment or careful follow-up examination should be considered.

Adult↗

Identification of novel missense mutations (Phe310Leu and Gly439Arg) in a neonatal case of hypophosphatasia.

Hypophosphatasia is associated with a defect of the tissue-non-specific alkaline phosphatase gene. We performed a mutational analysis in a surviving patient diagnosed at birth as having hypophosphatasia, on the basis of a low level of serum alkaline phosphatase (ALP) activity and characteristic radiographical findings. She had two sisters, one of whom died of respiratory failure complicated by perinatal hypophosphatasia; the other seemed healthy, with a relatively low activity level of ALP. The patient's parents also had low ALP activity. Sequence analysis of the tissue-nonspecific alkaline phosphatase gene was performed, using genomic DNA and total RNA from the skin fibroblasts of the patient and the peripheral mononuclear cells of her parents. The conversion of Phe to Leu at codon 310 (F310L) and Gly to Arg at 439 (G439R) were identified in the patient. Interestingly, the reconstructive experiments demonstrated that the F310L mutant exhibited an ALP activity level 65% of the normal level, whereas the mutant G439R had no activity. Moreover, the digestion by StuI, after a PCR using complementary DNA extracted from fibroblasts of the patient and lymphocytes of her father, revealed a relatively low messenger RNA level of F310L. These findings suggest that the neonatal case of hypophosphatasia was associated with compound mutations, one of which caused the loss of ALP activity and the other of which caused a slight reduction of the ALP activity, with a relatively low level of messenger RNA.

Adult↗