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Biomedical subjects

K Harada

Publications and source records attributed to K Harada.

At least 829 records · Page 46Linked to original sources

Activity of a novel thienodiazepine derivative as a platelet-activating factor antagonist in guinea pig lungs. Effects on platelet-activating factor and allergen induced eosinophil accumulation.

Platelet-activating factor (PAF) inhalation in guinea pigs caused a significant increase in the number of eosinophils recovered from bronchoalveolar lavage fluid (BALF). Oral administration of (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4]diazepine (E-6123), a novel PAF antagonist, at the dose of 100 micrograms/kg completely inhibited the PAF-induced eosinophil accumulation. Antigen inhalation in passively sensitized guinea pigs caused a significant increase in lung contents of PAF at 5 min, and accumulation of eosinophils in the bronchi 1 and 2 days thereafter, E-6123 inhibited the antigen-induced eosinophil accumulation and the maximum inhibition was approximately 65%. On the other hand, methylprednisolone completely inhibited the antigen-induced eosinophil accumulation. The results suggest that PAF is a potent attractant of eosinophils and is involved in antigen-induced eosinophil infiltration into bronchi. The results also suggest that E-6123 may be of therapeutic value in the treatment of asthma exhibiting eosinophil recruitment in airways.

Aerosols↗

[Evaluation of SPECT with N-isopropyl [I-123]-p-iodoamphetamine (IMP) or technetium-99m [99mTc]-d,l-hexamethylpropyleneamine oxime (d, 1-HM-PAO) in cerebral concussion].

123I-IMP and Tc-PAO SPECT were performed in 20 cases of cerebral concussion ranging in age from 4 to 20 years old, including six cases of the juvenile head trauma syndrome (JHTS). The SPECT findings were divided into two main types: six cases in the normal group with no blood flow abnormalities, and 14 cases in abnormal group showing reduced blood flow, mainly in cerebellum and occipital lobe except in one case. In 10 cases with reduced blood flow which could be analyzed, calculation of the blood flow ratio in the temporal and occipital lobes and the cerebellum with the frontal lobe taken as 100 showed values of 93.5% for the temporal lobe, 82.7% for the occipital lobe and 76.8% for the cerebellum. A statistically significant reduction in blood flow occurred in the occipital lobe and cerebellum. In blood examination, abnormally high values of white blood cell counts were observed transiently in 94% of cerebral concussion cases. Abnormalities in brain stem and hypothalamus appeared to cause these abnormal WBC values. From these findings, it was suggested that the blood flow regions of the basilar and posterior cerebral arteries, i.e., the brain stem and hypothalamus are closely connected with the lesions responsible for cerebral concussion. It also appeared that the JHTS occurs in cerebral concussion cases where recovery of the abnormal blood flow in these regions in poor.

Adolescent↗

[Effect of gastrectomy on release of gut hormones].

We investigated the effect of gastrectomy on the digestive system in 87 postoperative long-term survivors under test meal or egg yolk load. After test meal, gastrin and secretin responses were decreased in each of groups of proximal gastrectomy (PG), distal gastrectomy with Billroth-I (DG-B1), that with Billroth-II (DG-B2), total gastrectomy with interposition (TG-I), and that with Roux-Y (TG-RY). However, sufficient acid-secretors after partial gastrectomy showed secretin responses comparable to controls. Furthermore, cases of total gastrectomy given betain-hydrochloride with test meal increased secretin responses. Serum glucose response was higher in the TG-RY group while insulin response was high in the TG-RY and DG-B2 groups, compared with controls. GLI response was high in all groups compared with controls. Postgastrectomy gallstone occurred in 11.6%. Yolk-induced contraction of the gallbladder was decreased, and CCK release increased, for several years postoperatively. Gallbladder contraction with CCK was reduced for one year postoperatively. The contraction was reduced in persons with gallstone than those without it. This study shows that the digestive function after gastrectomy depends on acidification and duodenal passage of food, and that reduced contraction with CCK plays an important role in hypokinesis of the gallbladder.

Animals↗

[Computer assisted neurosurgery: development of a frameless and armless navigation system (CNS navigator)].

We have developed a computer assisted neurosurgical navigation system, which displays the point of ongoing surgical manipulation on the CT or MR images. The system utilizes magnetic field modulation technology for the detection of the 3 dimensional position and orientation angles of the probe, a resin pointer or suction tube with a small magnetic field sensor. Four fiducial markers on the scalp were used to translate the spatial data of the probe onto the CT/MRI images. This frameless and armless navigator with a spatial accuracy of 4mm, introduces CT/MRI-stereotaxy to conventional open neurosurgery without limiting the operative field or interfering with surgical procedures.

Adult↗

Oxidation-labile subfraction of human plasma low density lipoprotein isolated by ion-exchange chromatography.

We isolated subfractions of human plasma low density lipoprotein (LDL) using ion-exchange chromatography. Plasma LDL from normolipidemic subjects were applied to a DEAE Sepharose 6B column. After elution of the bulk of LDL at 150 mM NaCl (the major fraction), the residual LDL was eluted at 500 mM NaCl and designated as the minor fraction. The minor fraction, only less than 1% of total LDL, tended to be somewhat similar in certain properties to oxidized LDL, e.g., an increased negative charge, higher protein/cholesterol ratio, and a higher flotation density than native LDL. These results were consistent with data reported by Avogaro et al. (1988. Arteriosclerosis. 8: 79-87). However, assays of 125I-labeled LDL binding activity for LDL receptors equal to that of the major fraction. Incorporation of [14C]oleate into cholesteryl ester [acyl-CoA:cholesterol acyltransferase (ACAT) activity] in mouse peritoneal macrophages incubated with the minor fraction was only slightly greater than that with the major fraction. Incubation of the minor fraction with 0.5 microM Cu2+ caused a remarkable stimulation of ACAT activity, while stimulation by the major fraction required incubation with 5 microM Cu2+, suggesting that the minor fraction was relatively labile to oxidation. The minor but definite presence of a plasma LDL subfraction more negative and susceptible to oxidation implicates the possibility of its association with atherogenesis.

Arteriosclerosis↗

[Dynamic MRI of liver tumors--evaluation by inversion recovery snap shot FLASH MR imaging].

We have studied 20 patients with liver tumor (hepatoma 12, hemangioma 6, metastatic tumor 2) using inversion recovery snap shot FLASH dynamic MR imaging. After intravenous injection of Gd-DTPA, serial 17 images were obtained during 7 minutes. Hepatoma showed central enhancement on early phase (0-20 sec) in 11 patients and absent or less enhancement than surrounding liver parenchyma on late phase (1-3 min) in 12 patients. Hemangioma showed peripheral enhancement on early phase in 6 patients, and slight to moderate enhancement on late phase in 5 patients. Peripheral slight enhancement were seen on late and delayed (5-7 min) phase in two patients with metastatic liver tumor. These characteristic enhancement patterns should facilitate differential diagnosis of liver tumors.

Aged↗

Effect of tumor necrosis factor/cachectin on the activity of the low density lipoprotein receptor on human skin fibroblasts.

We have investigated the effects of recombinant human tumor necrosis factor (TNF)/cachectin on the cellular binding of human low density lipoprotein (LDL) to human skin fibroblasts. When recombinant TNF was added to cultured cells, LDL binding doubled after 24 h of incubation. The effect of TNF was dose-dependent and its maximal effect was observed at concentrations of 1-10 ng/ml. TNF also stimulated the growth of human skin fibroblasts 1.6-fold. These results indicate that TNF increases LDL-receptor activity, which might be related to its stimulatory effect on cell growth.

Dose-Response Relationship, Drug↗

In vitro and in vivo effects of protein phosphatase inhibitors, microcystins and nodularin, on mouse skin and fibroblasts.

Three microcystins, YR, LR and RR and nodularin, all of which are hepatotoxic compounds, inhibited dose-dependently the activity of protein phosphatase 2A in and the specific [3H]okadaic acid binding to a cytosolic fraction of mouse skin, as strongly as okadaic acid. However, microcytins and nodularin did not induce any effects on mouse skin or primary human fibroblasts. Microinjection of microcystin YR into primary human fibroblasts induced morphological changes which were induced by incubation with okadaic acid. Microcystins and nodularin penetrate into the epithelial cells of mouse skin and human fibroblasts with difficulty, which reflects tissue specificity of the compounds.

Animals↗

Hippocampal neurotrophic factors influence the perikaryal size of septal acetylcholinesterase-containing neurons in culture.

The septal neurons were cultured under the following conditions: (1) treated with 7S nerve growth factor (NGF) (50 ng/ml); (2) grown with hippocampal cell-conditioned medium supernatant; (3) cocultivated with hippocampal cells; (4) cocultivated with cerebellar cells; (5) no treatment. Acetylcholinesterase histochemistry was used to identify cholinergic cells after pretreatment with diisopropylfluorophosphate. The mean values of the perikaryal major axis and minor axis at day 14 of culture were significantly larger in septal cells cocultivated with hippocampal cells than in septal cells grown under other conditions. NGF-treated septal cells showed a smaller, but significant, increase in the mean value of the major axis of these neurons.

Acetylcholinesterase↗

Monocyte colony-stimulating factor enhances uptake and degradation of acetylated low density lipoproteins and cholesterol esterification in human monocyte-derived macrophages.

We have investigated effects of monocyte colony-stimulating factor (M-CSF) on the uptake of acetylated low density lipoproteins (acetyl-LDL) and the activity of cholesterol esterification in human monocyte-derived macrophage. The cells were cultured with M-CSF for 10 days and then incubated with acetyl-LDL for 24 h. M-CSF (128 ng/ml) enhanced the uptake and degradation of 10 micrograms/ml of 125I-acetyl LDL 7.5-fold (n = 6) and the effect of M-CSF was dose-dependent at the concentrations of 0.5-32 ng/ml. The binding experiments at 4 degrees C demonstrated that the number of acetyl-LDL receptor was increased by the addition of M-CSF. Supporting this, ligand blotting analysis revealed a significant increase in a receptor protein for acetyl-LDL (240 kDa). Binding of LDL was also enhanced by M-CSF but less significantly than that of acetyl-LDL. Cellular cholesterol esterification in the presence of 10 micrograms/ml acetyl-LDL was enhanced 24.1-fold (n = 13) by 128 ng/ml M-CSF. It was evident that M-CSF enhanced cholesterol esterification to a greater extent than the cellular uptake of acetyl-LDL (24.1- versus 7.5-fold). Cholesterol esterification was also enhanced by the addition of granulocyte-macrophage colony-stimulating factor and interleukin 1. We conclude that M-CSF enhances the uptake of both acetyl-LDL and LDL by increasing their receptor number, and further enhances the process of cholesterol esterification, resulting in a remarkable increase in cholesterol esterification in macrophages. These findings strongly suggest the significant involvement of cytokines such as M-CSF in cholesterol metabolism of macrophages.

Biological Transport↗

[Effects of sampling bandwidth in MR imaging].

Phantom and volunteer study was performed with spin-echo sequences of different sampling bandwidths to evaluate the narrow bandwidth signal acquisition technique. Our results demonstrated the characteristics of the narrow bandwidth sequence as follows: SNR improvement, sensitive to the field inhomogeneity and motion, loss of edge definition for short T2 tissues, and prominent chemical shift artifacts. Narrow bandwidth sequence with flow compensation was suitable for brain T2 weighted images because of its high SNR and less artifacts. In spite of the improvement of SNR, the narrow bandwidth technique may be inappropriate for short T2 tissues such as muscle, because of prominent chemical shift artifacts and loss of edge definition. Consequently, sampling bandwidth is one of the parameters which can be manipulated to improve MR image quality.

Brain↗

Human monocyte colony-stimulating factor enhances the clearance of lipoproteins containing apolipoprotein B-100 via both low density lipoprotein receptor-dependent and -independent pathways in rabbits.

To investigate the effects of recombinant human monocyte colony-stimulating factor (M-CSF) on plasma cholesterol metabolism, we injected M-CSF intravenously into New Zealand White rabbits (n = 13) at a dose of 100 micrograms/day for 7 days. After the treatment, the plasma cholesterol levels fell by 33.2% from 61.4 +/- 25.9 to 41.0 +/- 10.2 mg/dl (mean +/- S.D.). We also injected a large dose of M-CSF (500 micrograms/day) for 6 days into Watanabe Heritable Hyperlipidemic rabbits, which are deficient in low density lipoprotein (LDL) receptors. Again, there was a significant reduction in plasma cholesterol levels by 36.2% from 730.5 +/- 176.4 to 466.0 +/- 104.9 mg/dl (n = 4). In the kinetic studies in New Zealand White rabbits with very low density lipoprotein, LDL, and methylated LDL, the removal rates of those lipoproteins were increased 1.9-, 1.7-, and 2.0-fold, respectively, after the treatment. Immunoblot analysis of LDL receptors in the treated rabbits showed no significant changes in LDL receptor proteins in livers but a great increase in spleens and bone marrows compared with the controls. Messenger RNA was also estimated by Northern blotting in both groups, and the results were compatible with those from the immunoblot. The data suggest that M-CSF stimulates the clearance of lipoproteins containing apolipoprotein B-100 via both LDL receptor-dependent and -independent pathways in target cells of M-CSF and reduces plasma cholesterol.

Animals↗

[A short TE gradient-echo sequence using asymmetric sampling].

We have developed a gradient-echo pulse sequence with a short TE less than 4 msec using a data set of asymmetric off-center sampling with a broad bandwidth. The use of such a short TE significantly reduces T2* de-phasing effect even in a two-dimensional mode, and by collecting an off-center echo, motion-induced phase dispersion is also considerably decreased. High immunity of this sequence to these dephasing effects permits clear visualization of anatomical details near the skull base where large local field inhomogeneities and rapid blood flow such as in the internal carotid artery are present.

Brain↗

[A clinicopathological analysis of renal cell carcinoma in solitary kidney].

Seven patients with renal cell carcinoma, who had undergone uninephrectomy or who had only one functioning kidney were clinicopathologically studied. They were 5 males and 2 females, with ages ranging from 51 to 74 years (mean: 61 years). Of these cases, 4 had undergone uninephrectomy for renal cell carcinoma, and 1 had received uninephrectomy because of renal calculus. In the remaining 2 cases, one kidney did not function (hypoplastic kidney). Renal cell carcinoma was discovered by macroscopic hematuria in 2 cases, during the follow-up observation after a previous surgical treatment of renal cell carcinoma in 4 cases and by abdominal computed tomography during treatment of abdominal aneurysm in 1 case. Excluding one case with multiple metastases, all cases were surgically treated (3 with partial nephrectomy and 3 with enucleation). During surgery, renal blood vessels were clamped for 24-60 minutes (mean: 38 minutes). After operation, 5 cases showed an elevation in serum creatinine (greater than or equal to 2.0 mg/ml), which, however, was normalized rapidly by conservative treatment. They have been followed up for 6 months to 7 years and 8 months after operation (mean: 2 years and 11 months). The case which had undergone before and recently received enucleation (2 pieces) showed metastasis of cancer to the pancreas 2.5 years after the recent operation. Therefore, this case additionally received partial pancreatectomy. The results of this study suggest that conservative surgical treatments are appropriate for the treatment of renal cell carcinoma in patients with solitary kidney from viewpoint of the quality of life, so long as postoperative management is sufficiently made.

Aged↗