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Biomedical subjects

K Endo

Publications and source records attributed to K Endo.

At least 19 recordsLinked to original sources

Binding of vitamin D to low-density-lipoprotein (LDL) and LDL receptor-mediated pathway into cells.

The present study was undertaken to identify serum components other than vitamin D-binding proteins that bind to 1,25(OH)2 D3, and its analog. The binding rate of 1,25(OH)2 D3, 22-oxa-1,25(OH)2D3 (OCT) or 25(OH) D3 to total lipoprotein(TLP) represented 16.7%, 4.65%, and 3.11% of total counts added, respectively. Polyacrylamide gel electrophoresis of the TLP revealed that 1,25(OH)2 D3 and OCT were associated with LDL. The binding studies of OCT-bound LDL to the fibroblasts showed specific pathway to the cells mediated by LDL-receptor. These findings may have important implications in understanding the mechanisms of the diverse biological actions of 1,25(OH)2 D3 and in designing a novel delivery system for vitamin D analogs.

Apolipoprotein B-100

Vestibular inputs to the lateral tegmental field of the cat: potential role in autonomic control.

The lateral tegmental field (LTF), which is comprised of the lateral reticular formation near the obex, is an important integrative area involved in cardiovascular control and the production of emesis. Using neuroanatomical and electrophysiological techniques, we tested the hypothesis that LTF neurons receive vestibular inputs; the neurons studied included those projecting into the subretrofacial rostral ventrolateral medulla (sRVLM), which contains cells that make direct connections with sympathetic preganglionic neurons. Injections of the anterograde tracer PHA-L into the medial and inferior vestibular nuclei produced labeled terminals in the LTF. Electrical stimulation of the vestibular nerve affected the firing rate of LTF neurons, including approximately one-third of those antidromically activated from the sRVLM. The response latencies ranged from 1.5 to 20 ms, suggesting that the neurons received both direct and polysynaptic vestibular inputs from the vestibular nuclei. The LTF may be involved in the production of vestibulosympathetic reflexes and vestibular-elicited vomiting.

Animals

GTP cyclohydrolase I gene in hereditary progressive dystonia with marked diurnal fluctuation.

We previously reported four different mutations in the coding region of GTP cyclohydrolase I (GCH-I) gene in patients with hereditary progressive dystonia with marked diurnal fluctuation (HPD). We found two independent new mutations (leucine 79 proline and a deletion in exon 4) in patients with HPD. We also found four families of HPD without any mutations in the coding region of GCH-I gene.

Base Sequence

Remarkable activity enhancement of thermolysin mutants.

Most attempts to modify the properties of enzymes by amino acid substitution around the active sites have resulted in suppression of the biological activity, suggesting that the structure of natural enzymes should be almost optimized evolutionally to show the highest activity. In contrast, we found an interesting site of a well-known metalloendopeptidase, thermolysin (EC.3.4.24.4), where almost all the amino acid replacement causes a remarkable increase in the hydrolytic activity. Negative correlation between the activity and the thermal stability was observed. The flexibility around the substrate binding site is suggested to be a key to the correlation. Nature may have selected the amino acid at this site, which suppresses the flexibility of the molecule, to get the highest thermal stability at the expense of the activity.

Enzyme Activation

Axonal projections of utricular afferents to the vestibular nuclei and the abducens nucleus in cats.

Axonal projections of utricular (UT) afferents in cats were examined by three approaches: recordings of field potentials, labelling of UT nerve fibres by localized infusion of horseradish peroxidase (HRP) and intraaxonal infusion of HRP into a single UT afferent. UT afferents project principally into the rostral part of the descending nucleus and the ventral part of the lateral nucleus. Projection into the superior and the medial nuclei and the ipsilateral abducens nucleus were also observed.

Abducens Nerve

The gene for hereditary progressive dystonia with marked diurnal fluctuation maps to chromosome 14q.

Hereditary progressive dystonia with marked diurnal fluctuation (HPD) is a childhood-onset, postural dystonia that is characterized by marked diurnal fluctuation and a dramatic response to levodopa. Recently, the gene for dopa-responsive dystonia (DRD), an autosomal dominant dystonia showing similarly marked response to levodopa, has been mapped to chromosome 14q. Since HPD and DRD share many clinical characteristics, we have analyzed microsatellite polymorphisms in the region of the DRD locus and obtained a maximal lod score of 2.0 at D14S52 without obligate recombination events in the affected individuals. The results strongly suggest that HPD and DRD are to be caused by mutations in the same gene on the long arm of chromosome 14.

Chromosome Mapping

Mechanism of inhibition of IgE-dependent histamine release from rat mast cells by penasterol and penasterone.

Penasterol and penasterone, constituents of the Okinawan marine sponge Penares incrustans, dose-dependently inhibited anti-IgE-induced histamine release from rat mast cells. The concentrations of penasterol and penasterone required for 50% inhibition of anti-IgE-induced histamine release (IC50) were 0.5 and 1.5 microM, respectively. Both compounds dose-dependently inhibited phospholipase A2 (PLA2) activity. Moreover, they inhibited anti-IgE-induced [3H]arachidonic acid from rat mast cells. These results suggest that the mechanism of inhibition by these compounds of the histamine release induced by anti-IgE was through the inhibition of PLA2.

Animals

A novel translocation involving chromosomes 2, 9, 14, and 22 in chronic myeloid leukemia.

A 46-year-old man with chronic myelogenous leukemia was found to have a new complex translocation. In chronic phase, all of the bone marrow cells had a rearrangement of a t(2;9;14;22) (p21;q34;q32;q11). Southern blot analysis of leukocyte DNA revealed rearrangement of the breakpoint cluster region (bcr) within the 5.8-Kb bcr. The patient eventually died in blast crisis 28 months later. The cytogenetic findings of bone marrow cells showed a 46,XY,t(2;9;14;22)(p21;q34;q32;q11),add(1p),del(3q) karyotype in blast crisis.

Chromosome Banding

Endothelium-derived hyperpolarizing factor does not contribute to the decrease in endothelium-dependent relaxation in the aorta of streptozotocin-induced diabetic rats.

1. We examined the contribution of endothelium-derived hyperpolarizing factor (EDHF) to the impairment of endothelium-dependent relaxation caused by acetylcholine (ACh) in the aorta of streptozotocin-induced diabetic rats, by using N omega-L-nitro-arginine methylester (L-NAME) and tetraethylammonium chloride (TEA) to inhibit nitric oxide (NO) and EDHF, respectively. 2. ACh-induced relaxation of the aorta decreased in diabetic rats. In contrast, sodium nitroprusside-induced relaxation was the same in diabetic rats and control rats. 3. Treatment with 5 x 10(-7) M L-NAME resulted in a right shift of the dose-response curves of ACh-induced relaxation in the aorta. The shift was greater in the control aorta. 4. Treatment with 5 x 10(-4) M TEA resulted in a similar right shift in both the control and diabetic aorta. 5. Therefore, while endothelium-derived NO appears to contribute to the impairment of ACh-induced endothelium-dependent relaxation in the aorta of diabetic rats, EDHF does not.

Acetylcholine

Repeating the avidin "chase" markedly improved the biodistribution of radiolabelled biotinylated antibodies and promoted the excretion of additional background radioactivity.

Immunoscintigraphy using radiolabelled biotinylated monoclonal antibodies followed by infusion of avidin as a "chase" has been recently reported to improve the biodistribution for both immunoscintigraphy and radioimmunotherapy. In this study the circulating protein-bound and avidin-binding fractions of radiolabelled biotinylated antibodies were determined serially after injection of an avidin "chase", and the effect of repeating the avidin chase was also studied. Nude mice bearing KT005 human osteogenic sarcoma were injected with radiolabelled biotinylated antitumour monoclonal antibody (OST7). After injection of an avidin chase, the protein-bound and avidin-binding fractions in plasma were determined serially using the trichloroacetate method and avidin-Sepharose gel. The biodistribution of radiolabelled biotinylated OST7 was compared after single and double avidin chases with no chase. At 6 h after the first avidin chase in mice injected with radioiodinated and technetium-labelled biotinylated OST7, 67.7% and 67.8%, respectively, of the plasma radioactivity was available for binding to avidin and was cleared from the circulation. Reinjection of avidin decreased the plasma radioactivity and improved the biodistribution of the radiolabelled biotinylated antibodies. Repeating the avidin chase markedly improved the biodistribution of the radioiodine-labelled biotinylated antibody when compared with the use of a single avidin chase. This new method for radioimmunotherapy is sure to protect the critical organs from radiation injury without decreasing the therapeutic effect.

Animals

Synthesis and preliminary evaluation of [11C]KF15372, a selective adenosine A1 antagonist.

As a radioligand for mapping the presynaptic adenosine A1 receptors in the central nervous system by PET, [1-propyl-11C]8-dicyclopropylmethyl-1,3-dipropylxanthine ([11C]KF15372), a selective adenosine A1 antagonist, was prepared by the reaction of 8-dicyclopropylmethyl-3-propylxanthine and [11C]propyl iodide with decay-corrected radiochemical yield of 5% based on the [11C]propyl iodide, radiochemical purity of > 99%, sp. at. of 10-56 GBq/mumol and preparation time of 45-55 min. Another 11C-labeled A1 antagonist with much lower affinity for the A1 receptors, 7-[11C]methyl-KF15372 ([11C]KF17109), was also prepared using [11C]methyl iodide with a decay-corrected radiochemical yield of > 50%. In mice, the brain uptake of [11C]KF15372 (1.91% ID/g at 5 min) decreased gradually with time. Carrier KF15372 competitively reduced the brain uptake to a level (43% of the control) comparable to the brain uptake of [11C]KF17109. On the other hand, an A2 antagonist 3,7-dimethyl-1-propargylxanthine showed no effect on the brain uptake of [11C]KF15372. The results show that [11C]KF15372 has potential as a PET radioligand for mapping the adenosine A1 receptors and that [11C]KF17109 may be a reference compound reflecting the non-specific uptake of the [11C]KF15372.

Animals

Kinetics of platelets in dogs with thrombocytopenia induced by antiglycoprotein IIb/IIIa receptor monoclonal antibody.

To experimentally assess the kinetics of platelets in thrombocytopenia, we constructed a canine model using 111In-oxine labeled autologous platelets and an intact antiplatelet monoclonal antibody (MAb) NNKY2-11 (IgG2a). With the infusion of radiolabeled autologous platelets into dogs, the peripheral platelet count and blood radioactivity level were examined, and the radioactivity in the liver, spleen and heart was determined with scintigraphic analysis. Thereafter, i.v. injection of 100 micrograms/kg of NNKY2-11 had no effect on platelet counts or the biodistribution of radiolabeled platelets. However, 200 and 300 micrograms/kg of MAb reduced the platelets, and the radioactivity of the liver and spleen augmented clearly after injection of MAb. Platelet radioactivity in serum, which had decreased after MAb infusion, did not recover, even when peripheral platelet counts returned to the normal levels, indicating that these new platelets might be derived from the platelet-storage pool or new thrombocytogenesis. This model of antiplatelet MAb induced thrombocytopenia seems to be useful for analyzing the kinetics of platelets in thrombocytopenia.

Animals

A tumour-associated cell-surface glycoprotein accompanying p53 overexpression and higher growth potential for gastric cancer.

Tumour-associated cell-surface glycoprotein is associated with tumour progression in gastric cancer. We investigated the biological significance of tumour-associated cell-surface glycoprotein, determined by the binding of Helix pomatia agglutinin (HPA), with regard to survival time and to the malignant potential of cancer cells in serosally invasive gastric cancer in 119 patients. HPA was positively stained in 75 of 119 patients (63.0%) with gastric cancer with serosal invasion. In patients with HPA-positive tissue, the tumour was larger than in HPA-negative cases and was frequently located in the middle third of the stomach. The incidence of lymph node metastasis was higher than in patients with HPA-negative tissue. There were no differences between the cases staining negatively and positively with HPA with respect to the other factors examined. Gastric cancer tissues with HPA-positive staining revealed a higher positive rate of abnormal p53 staining and a higher concentration of proliferating cell nuclear antigen (PCNA) labelling. The survival time of the patients with HPA positive staining was shorter than for those whose tissues were HPA negative. Thus, tumour-associated cell-surface glycoprotein is apparently closely related to the malignant potential of serosally invasive gastric cancer.

Aged

Discordant findings between krypton-81m gas and Tc-99m labeled ultrafine aerosol lung ventilation SPECT in two patients with idiopathic pulmonary fibrosis.

Technegas, a newly developed ultra-fine dry dispersion of Tc-99m labeled carbon with a particle size of approximately 5 nm to 20 nm, possesses the properties for lung ventilation imaging using SPECT. The authors observed a discrepancy between krypton-81m gas and technegas lung ventilation SPECT in two patients with idiopathic pulmonary fibrosis who demonstrated heterogeneously decreased distribution of technegas without regions of high count density (focal hot spots) of tracer in their lungs in spite of the almost homogenous distribution of krypton-81m gas. This finding could be explained by the duration of radioactive gas inhalation. Technegas lung ventilation SPECT images reflected lung ventilation with tidal breathing. Conversely, Kr-81m gas lung ventilation SPECT images reflected not only lung ventilation, but also lung volumes. These two radioactive agents for lung ventilation SPECT show different findings.

Administration, Inhalation

Diagnostic value of Tc-99m (V) DMSA for chondrogenic tumors with positive Tc-99m HMDP uptake on bone scintigraphy.

Technetium-99m (V) DMSA scintigraphy was performed in 17 patients with 37 chondrogenic tumors (13 osteochondromas, 14 enchondromas, and 10 chondrosarcomas) that had previously shown uptake of Tc-99m HMDP. Technetium-99m (V) DMSA showed high uptake by all chrondrosarcomas, but low or no uptake always indicated benign chondrogenic tumors. Technetium-99m (V) DMSA scintigraphy may be superior to Tc-99m HMDP scintigraphy for distinguishing benign and malignant chondrogenic tumors, and could also be useful for diagnosing the malignant transformation of chondrogenic tumors.

Bone Neoplasms

Increased pulmonary clearance of aerosolized 99Tcm-DTPA in patients with a subset of stage I sarcoidosis.

Measurement of the pulmonary clearance of aerosolized 99Tcm-diethylenetriamine pentaacetate (99Tcm-DTPA) as a marker of pulmonary parenchymal damage was performed in 10 non-smokers with sarcoidosis, none of whom was on medication, and the results compared with 12 normal controls. Posterior images were obtained using a single-headed gamma camera, with the subjects in a supine position, for 30 min after inhalation of aerosolized 99Tcm-DTPA had ceased. The pulmonary clearance of 99Tcm-DTPA was significantly increased in the sarcoidosis patients (57.6 +/- 22.1 min in the right lung, 62.2 +/- 22.7 min in the left lung) compared with the controls (79.3 +/- 10.2 and 78.4 +/- 7.7 min in the right and left lungs, respectively) (P < 0.05). Six of the 10 patients with sarcoidosis showed levels of pulmonary clearance, in both the right and left lungs, below the 95.5% confidence limit (mean +/- 2 S.D.) for the controls. Increased pulmonary clearance of 99Tcm-DTPA was also found in 2 of 4 patients with stage I sarcoidosis. No relationship was found between the pulmonary clearance of 99Tcm-DPTA and inflammatory markers (ACE, lysozyme) in the serum.

Adult

Comparison of the chase effects of avidin, streptavidin, neutravidin, and avidin-ferritin on a radiolabeled biotinylated anti-tumor monoclonal antibody.

Injection of avidin can decrease the background radioactivity due to a radiolabeled biotinylated monoclonal antibody. We compared the chase effects of avidin, streptavidin, neutravidin, and avidin-conjugated ferritin on a radiolabeled antitumor monoclonal antibody in tumor-bearing nude mice. A radioiodine-labeled biotinylated monoclonal antibody (OST7) was administered to athymic mice bearing osteogenic sarcomas. After 24 h, an avidin, streptavidin, neutravidin or avidin-conjugated ferritin chaser was intravenously injected into the mice. At 2 h after the chase, the biodistribution of the radiolabeled monoclonal antibody was determined. Clearance from the blood was dose-dependently accelerated by avidin and its effect was 10-fold stronger than that of neutravidin or avidin-ferritin. Streptavidin did not promote clearance of the biotinylated antibody. Avidin was the most effective chasing agent for improving the biodistribution of the radiolabeled biotinylated monoclonal antibody among the four avidin derivatives tested.

Animals

Hemodialysis: relationship between signal intensity of the posterior pituitary gland at MR imaging and level of plasma antidiuretic hormone.

PURPOSE: To investigate the correlation between signal intensity of the posterior pituitary gland on magnetic resonance (MR) images and levels of plasma antidiuretic hormone (ADH) in patients undergoing hemodialysis. MATERIALS AND METHODS: The cases of 25 patients undergoing hemodialysis (15 men and 10 women, aged 24-75 years [mean, 51 years]) were prospectively evaluated. Laboratory testing and MR imaging were performed both before and after hemodialysis in 14 patients and only before hemodialysis in 11 patients. RESULTS: Before hemodialysis, nine patients (36%) had normal hyperintensity in the posterior pituitary gland, with almost normal plasma ADH levels and slightly elevated plasma osmolality. In six patients (24%) with less hyperintensity than is characteristic in the posterior pituitary gland, plasma ADH levels were slightly increased or normal. In 10 patients (40%) with an isointense posterior pituitary gland, plasma ADH and osmolality levels were evaluated. CONCLUSION: Elevated plasma osmolality may cause increased plasma ADH concentration and a lack of hyperintensity in the posterior pituitary gland at MR imaging.

Adult