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Biomedical subjects

N Sakai

Publications and source records attributed to N Sakai.

At least 379 records · Page 21Linked to original sources
PubMed1996

[Assessment of thalamic regional cerebral blood flow in patients with cerebrovascular disease].

The thalamus is believed to play an integrative role in the central nervous system. In the present study, thalamic rCBF was measured in 65 CVD patients and 15 normal volunteers by stable Xe/CT scanning. ROIs were chosen in the thalamic slice at a level 5cm over the OM line, and mean CBF was 7 cm over the OM line. The clinical factors focused on in multiple regression analysis were: age (A), sex (Se), stage from onset (St), lesion side (Sd); unilaterality or bilaterality, size (Sz) thalamic lesion (Tl). GCS (G), HDS-R (H); Hasegawa dementia score (revised), symptoms (Ss) such as anxiety, dizziness, head-headed feeling and headache, and neurological deficits (N). Each factor was graded and scored. Statistically, there was a significant correlation between thalamic rCBF (Y) and mean CBF (X) in the less affected hemisphere: Y = 1.82X + 2.2, r = 0.801, p < 0.001, n = 65. Multiple regression analysis of the thalamic rCBF revealed that the Sz factor was significant (p < 0.0001) on the lesion side: Y = 76.7-10.2Sz, r = 0.644, p < 0.001, n = 51, while the Se, Sd and St factors were significant (p < 0.005) on the less affected side: Y = 71.9 + 9.7Se-6.8Sd-5.0St, R = 0.585, p < 0.001, n = 65. The thalamic index (X), an indicator of thalamic atrophy, and thalamic rCBF were significantly correlated: Y = 28.7X + 10.2, r = 0.386, p < 0.001, n = 80. In conclusion, thalamic rCBF appeared to reflect the degree of organic changes and time course in the cerebral hemisphere, because factors such as size, sex and stage were statistically significant.

Cerebral Infarction↗
PubMed1996

[The dose-response relationship in treatment of strabismus with botulinum toxin].

The dose-response relationship between botulinum toxin and the alteration of ocular alignment of 15 esotropia cases (ET) and 15 exotropia cases (XT) was evaluated. We began with a dose of 0.25 units (U) per injection and stepped it up to 2.5 U per injection in ET and to 10 U per injection in XT. The average number of injections was 3.6 and 5.2, respectively. The maximum effect on ocular alignment developed 7 to 14 days after injection, and following recurrences ceased within 2 to 6 months, indicating a lasting effect. The maximum effect of each injection was within the limits of 10 to 30 prism diopters (delta). The maximum effect per unit dose of the small dose injection was greater than that of the large dose injection. In each dose, a greater effect was observed in the ET than in the XT, Recurrence was within the limits of 8 to 21 delta with both small dose injection and large dose injection. The recurrence amount per unit dose was greater with small dose injection than with large dose injection. The larger the dose injected, the more lasting was the effect obtained. This tendency was more prominent in ET than in XT. A roughly linear relationship between the dose and the ocular alignment was obtained on logarithmic graph paper, and the recurrence was reduced when the dose was increased. These findings suggest that repetitive injection effectively accumulates, resulting in a lasting effect.

Adolescent↗
PubMed1996

Exon 10 skipping caused by intron 10 splice donor site mutation in cholesteryl ester transfer protein gene results in abnormal downstream splice site selection.

Cholesteryl ester transfer protein (CETP) deficiency is the most common cause of hyperalphalipoproteinemia in Japan. However, the genetic basis of this disorder has not been fully characterized. We have studied a 49-year-old Japanese male presenting with total cholesterol, HDL-cholesterol, and apolipoprotein A-I levels of 300, 236, and 233 mg/dl, respectively, and total absence of CETP activity and mass in plasma. Sequence analysis of the patient's CETP gene revealed that the splice donor consensus GT was substituted by GG in intron 10 (intron 10 splice defect) and by AT in intron 14 (intron 14 splice defect). Restriction digestion of PCR-amplified DNA using NdeI and MaeIII established that the patient was a compound heterozygote for both gene defects. Sequencing of cDNA amplified by RT-PCR from the patient's monocyte-derived macrophage RNA demonstrated abnormal splicing with deletion of exon 10 as well as alternative splicing at a native AG site located 31 nucleotides 5' of the normal splice acceptor in intron 13. Thus, the intron 10 splice defect results in exon 10 skipping and the insertion of a 31 bp fragment between exon 13 and exon 14, which contains an in frame stop codon. The presence of abnormally spliced mRNA was further confirmed by amplification of patient cDNA using CETP specific primers. Abnormal splicing of exon 14 as a result of the intron 14 splice defect was not detected, indicating potential unstable CETP mRNA derived from that mutation. These findings demonstrate that a novel splice site mutation in intron 10 of the CETP gene results in the skipping of exon 10, as well as disruption of downstream splicing at intron 13 identifying a novel mechanism leading to CETP deficiency.

Base Sequence↗
PubMed1996

A novel nonsense mutation (G181X) in the human cholesteryl ester transfer protein gene in Japanese hyperalphalipoproteinemic subjects.

Cholesteryl ester transfer protein (CETP) plays an important role in regulating the concentration and composition of high density lipoprotein (HDL) and low density lipoprotein (LDL). Although several genetic abnormalities causing CETP deficiency have been identified in the Japanese subjects with a marked hyperalphalipoproteinemia (HALP), there are many CETP-deficient subjects for whom the genetic abnormalities have not been clarified. In the present study, we analyzed the molecular basis of an HALP subject without CETP activity and mass, and found a novel mutation in the CETP gene. This novel mutation (G181X) was a G-to-T substitution at codon 181 of exon 6 which replaced a codon for glycine (GGA) with a premature stop codon (TGA). The G181X mutation created a new cutting site by restriction enzyme MaeIII. To estimate the frequency of G181X, we investigated unrelated 294 HALP (HDL-cholesterol > or = 2.59 mmol/L = 100 mg/dl) subjects by restriction fragment length polymorphism (RFLP) analysis with Mae III. One (0.34%) HALP subject was homozygous and four (1.36%) were heterozygous for this mutation. The allelic frequency of a G-to-T substitution at codon 181 of exon 6 was 0.0102 in HALP subjects. From the lipid analysis of the proband and the homozygote, it was clarified that the G181X mutation had dominant effects on HDL and LDL metabolism, similar to a G-to-A substitution at the 5' splice donor site of the intron 14 (1451 + 1G-->A). In conclusion, the G181X mutation is one of causes of HALP in the Japanese HALP subjects, having dominant effects on lipid metabolism.

Carrier Proteins↗
PubMed1996

[A case study of immunohistochemical findings of rheumatic pseudocystic lesions in the femoral lateral condyle and tibial plateau--the comparison with synovial lesions].

Rheumatoid pseudocysts of which pathogenesis are not well known, are commonly observed in the major joints of the body, especially knees in rheumatoid patients. This report investigated the pseudocysts in the knee of a rheumatoid patient radiologically and immunohistochemically. A sixty-three-year-old woman with rheumatoid arthritis who had pseudocysts in the femoral lateral condyle and tibial plateau was hospitalized to have the lesions surgically removed. The MRI findings showed a connection between the pseudocysts and the joint cavity. A window of 1 x 1 cm2 was made at the tibial anterior cortex and the contents of the pseudocyst were resected and hydroxyapatite granules were inserted into the lesion after the removal of the pseudocyst tissue. In the histological findings, the specimen from the tibial pseudocyst revealed fibrous connective tissue with a few inflammatory cells, while the synovial specimen revealed the fibrous tissue with intense inflammatory cells infiltration forming lymphoid follicules. In immunohistochemical findings, both specimens showed positive with anti-HLA class I, anti-HLA DR, anti-CD44 and anti-HSP70 antibodies. The pathological findings of the pseudocystic lesion were similar to those of synovia, and it was considered that the synovia had invaded into the bone and formed the pseudocystic lesion. The MRI findings also support this hypothesis. The pseudocystic lesion was surrounded by bone and it was isolated from cytokain-rich joint effusion. This isolation from rheumatic joint effusion may explain the weaker inflammation of the pseudocystic lesion than that of synovia.

Arthritis, Rheumatoid↗
PubMed1996

In vitro study of patellar position during sitting, standing from squatting, and the stance phase of walking.

Muscle balance in quadricep muscles is an important factor for patellar instability. However, in vivo, the activity of the quadriceps varies during knee motion. To simulate this clinical condition, different loading conditions of the rectus femoris, vastus lateralis, and vastus medialis oblique at different knee flexion angles were studied, and patellar motion during knee extension was determined. Seven fresh-frozen adult cadaver knees were use. Patellar motion in terms of patellar shift, patellar tilt, and rotation were measured using a magnetic tracker system. The loads applied to each quadriceps muscle were calculated using clinical electromyographical data for three activities: 1) knee extension while sitting, 2) standing from squatting, and 3) stance phase of walking. The patellar tracking in these three loading patterns was compared with that under constant loading of each quadriceps muscle. Each activity demonstrated a neutral patellar shift and tilt, as did the traditional constant loading. However, the patella in walking showed internal rotation when the rectus femoris was much weaker than the other vasti.

Adult↗
PubMed1996

Renal leiomyoma: a case report.

We report a case of renal leiomyoma. A 46-year-old woman was found incidentally to have a solid and cystic renal mass on computerized tomography. The angiogram revealed no neovascularity. Nephrectomy was performed. Histologically, it was diagnosed as renal leiomyoma of vascular type. Although preoperative diagnosis of renal leiomyoma is difficult due to the various radiological findings, we should always consider this tumor in the differential diagnosis of renal tumors.

Diagnosis, Differential↗
PubMed1995

Long-term depletion of brain histamine induced by alpha-fluoromethylhistidine increases feeding-associated locomotor activity in mice with a modulation of brain amino acid levels.

We examined the long-term effects of administration of (S)-alpha-fluoromethylhistidine (FMH), a specific inhibitor of histidine decarboxylase, on the spontaneous locomotor activity, food intake and brain contents of histamine, catecholamines, serotonin and amino acids of ICR mice. The distance of ambulation and number of rearings significantly increased from 8 to 15 h (20.00-03.00 h) after treatment with FMH (100 mg/kg, i.p.) and the 24-h food intake also increased significantly. On FMH treatment, the locomotor activity in movements of 3-15 cm/0.5 s was greater than that of control mice, whereas the number of slight movements (0-1 cm/0.5 s) decreased, suggesting that once a mouse treated with FMH is in motion, it moves a longer distance than a control mouse. We sacrificed mice 12 or 24 h after FMH treatment to measure the brain contents of histamine, monoamines and amino acids. Decrease of the brain histamine content to 35% of the control level was observed until 24 h after FMH treatment, but no significant changes in the brain catecholamine and serotonin contents were detected. However, the brain GABA content of ICR mice decreased to 85% of control 12 h after FMH treatment. Moreover, decrease of the brain GABA content after FMH treatment was greater in mast cell-deficient W/Wv mice, being 70 and 62% of the control level 12 and 24 h after treatment, respectively. The present experiments support the idea that the locomotor activity is affected by the central histaminergic system, directly and/or indirectly.

Amino Acids↗
PubMed1995

Flow cytometric analysis of serum deprivation-induced apoptosis of PC12 cells, with special reference to role of bcl-2.

To investigate the mechanism of serum deprivation-induced apoptosis in PC12 cells, we performed flow cytometry with the viable cell-specific fluorogen, fluorescein diacetate (FDA). Intact PC12 cells were positive when stained with FDA, and those cells were identical with the major population which possess larger forward and side scattered light. Apoptotic PC12 cells decreased the forward and side scatter light associated with the loss of FDA-positive cells. Nerve growth factor (NGF) and the bcl-2 protein protected the cells from serum deprivation-induced apoptosis. These data suggested that the process of apoptosis in PC12 cells can be analyzed with flow cytometry.

Animals↗
PubMed1995

Transferrin induces nitric oxide synthase mRNA in rat cultured aortic smooth muscle cells.

Incubation with holo-transferrin, but not apo-transferrin, induced the nitrite accumulation in the culture medium of rat aortic smooth muscle cells concentration- and time-dependently, which occurred after a lag period of 6 hours. The accumulation of nitrite was inhibited by N omega-nitro-L-arginine and cycloheximide, but not by calmidazolium. Ferric or ferrous iron had no effect on the accumulation. In reverse transcription-coupled polymerase chain reaction analysis, one amplified fragment (580 bp) corresponding to the inducible form of nitric oxide synthase (iNOS) mRNA was expressed after incubation with holo-transferrin for 10 hours. These results suggest that holo-transferrin activates expression of iNOS mRNA in rat aortic smooth muscle cells accompanied by nitric oxide accumulation via a pathway dependent on L-arginine in the culture medium.

Amino Acid Oxidoreductases↗
PubMed1995

Frequency of exon 15 missense mutation (442D:G) in cholesteryl ester transfer protein gene in hyperalphalipoproteinemic Japanese subjects.

Cholesteryl ester transfer protein (CETP) transfers cholesteryl ester from high density lipoprotein (HDL) to apo B-containing lipoproteins. The hyperalphalipoproteinemia caused by CETP deficiency is fairly common in Japan and one of the most common mutations in the CETP gene is the splicing defect of the intron 14, the allelic frequency of which has been shown to be 0.0049 in the Japanese general population. Recently, we have reported a missense mutation in exon 15 of the CETP gene (442D:G), showing a dominant effect on the CETP activity and HDL-cholesterol level. In the current study, we determined the frequency of this new mutation in Japanese hyperalphalipoproteinemic (HDL-cholesterol > or = 100 mg/dl) subjects. A rapid and easy screening method for this new mutation was developed using a polymerase chain reaction (PCR)-mediated site-directed mutagenesis. Among 117 Japanese hyperalphalipoproteinemic subjects (HDL-cholesterol; 116.7 +/- 16.5 mg/dl, mean +/- S.D.) without the intron 14 splice defect, three homozygotes (2.5%) and 34 heterozygotes (29.1%) were found to have the 442D:G mutation. The relative allelic frequency of this mutation was calculated to be 0.17. One of the homozygotes for the 442D:G mutation was the patient previously described by us as having hyperalphalipoproteinemia with corneal opacity and coronary heart disease. This was the first reported subject homozygous for the CETP deficiency who also demonstrated atherosclerotic symptoms. In homozygous subjects, CETP activity ranged from 37% to 62% of the normal value, which was consistent with the results obtained from the transient expression experiment previously reported; however, the specific activity of CETP was not as low as expected.(ABSTRACT TRUNCATED AT 250 WORDS)

Asian People↗
PubMed1995

Temporal profile of nuclear DNA fragmentation in situ in gerbil hippocampus following transient forebrain ischemia.

To determine the time course of nuclear DNA damage in the gerbil hippocampus following transient ischemia, brain sections 48, 72, 96 h and 7 days following 5 min ischemia were evaluated by a specific in situ labeling method of DNA breaks. After 72 h, only the neurons located in the medial part of the CA1 sector were labeled. And then, DNA damage extended to the lateral part of the sector with time.

Animals↗
PubMed1995

Differentiation between dysmyelination and demyelination using magnetic resonance diffusional anisotropy.

Using magnetic resonance (MR) diffusion-weighted method, we examined the optic and the trigeminal nerves of jimpy and twitcher mice, considered to be animal models of Pelizaeus-Merzbacher disease, hypomyelination disorder, and Krabbe disease, demyelination disorder, respectively. In jimpy mice, diffusional anisotropy of optic nerve did not show a significant difference compared to age-matched control mice, suggesting that diffusional anisotropy does exist in absence of multiple layers of myelin sheath. In twitcher mice, diffusional anisotropy was attenuated remarkably in the optic and trigeminal nerves. Loss of axonal straightness on longitudinal section confirmed by electron microscopy appeared to be the principal explanation for it. It is further suggested that this MR diffusion-weighted imaging method enables us to differentiate hypomyelination from demyelination in vivo.

Animals↗
PubMed1995

Effectiveness of intraoperative radiation therapy for recurrent supratentorial low grade glioma.

Twelve adult patients in the records of 38 patients with histologically verified supratentorial low grade glioma showed recurrence at the Gifu University Hospital between 1980 and 1992. A mean period to recurrence from the initial surgery and postoperative radiation was 38 months. Six of these patients underwent intraoperative radiation therapy. The other six patients received chemotherapy with conventional cytoreductive surgery in three cases and additional external irradiation in three cases. The 2-year survival rate of the former patients was 83.8% and significantly higher than that of the latter ones, 16.7% (p < 0.05). Most cases showing recurrence of supratentorial low grade glioma were occurred locally, and dissemination or remote metastasis of the lesion were rare. The results revealed that the local control is important for recurrent tumors of supratentorial low grade gliomas. The effectiveness of the intraoperative radiation therapy as the second operation for the recurrent supratentorial benign glioma is discussed.

Adolescent↗
PubMed1995

New design of N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) lung imaging in the patient with lung cancer.

N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) was injected intravenously into primary non small cell lung carcinoma patients (n = 17). The average pixel count ratios of the cancerous area to the whole lung was measured in the initial and delayed images. In the initial image, this ratio was less than 1.0 for the entire group of patients, and was thought to reflect decreased blood flow in the cancerous tissues. The rate of counts within a ROI in the delayed image to counts in the same ROI in the initial image was also calculated and called the remain rate. The remain rate (delayed count/initial count) was significantly higher in the cancerous area than in the whole lung (0.65 +/- 0.30, median 0.62, 0.38 +/- 0.05, median 0.38, p < 0.01). This observation was thought to be due to a relative decrease in the blood flow and the accumulation of IMP, which forms pools within the alveolar spaces of the cancerous areas. The image prepared with the remain rate revealed a hot image in the cancerous regions, even when this was not apparent in the delayed image. The remain rate image may therefore be useful in the identification of cancerous areas in lung tissue if it is used in comparison with the initial image.

Adult↗