[Adverse effect of sclerosants on the liver, kidney and lung].
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Esophageal and Gastric Varices↗
Biomedical subjects
T Okano
Publications and source records attributed to T Okano.
Effect of chloride ion on the thermal decay process of the batho intermediate of iodopsin at low temperature.
The photochemical and the subsequent thermal behaviors of iodopsin (Cl(-)-bound form) and N-iodopsin (iodopsin whose Cl- was replaced by NO3-) in CHAPS-phosphatidylcholine (PC) were studied by low-temperature spectrophotometry. Irradiation of the iodopsin preparation at -185 degrees C produced a photo-steady-state mixture composed of iodopsin, bathoiodopsin, and isoiodopsin. Bathoiodopsin was thermally reverted to the original iodopsin. These results were almost the same as those reported previously [Yoshizawa, T., & Wald, G. (1967) Nature 214, 566-571] in which iodopsin was extracted with 2% digitonin. Therefore, photochemical and subsequent thermal behaviors of iodopsin were independent of the detergent to solubilize iodopsin. Irradiation of N-iodopsin at -185 degrees C produced the similar photo-steady-state mixture. However, N-bathoiodopsin was thermally converted to the next intermediate, presumably N-lumiiodopsin. These results suggest that the batho-lumi transition of iodopsin at low temperature is likely to be inhibited by the Cl- bound to the protein moiety of iodopsin, while at room temperature the Cl- bound to iodopsin could be released on the conversion process of batho- to lumiiodopsin.
Animals↗
Stabilization of disulfide linkage in drug-polymer-immunoglobulin conjugate by microenvironmental control.
The stability of disulfide linkage in the conjugate composed of the anti-cancer agent adriamycin, poly(ethylene glycol)-poly(aspartic acid) block copolymer, and immunoglobulin G was studied. The disulfide linkage between the block copolymer and immunoglobulin G was found to be resistant to reduction with dithiothreitol (DTT). This extraordinary resistance is considered to be brought about by steric hindrance of the poly(aspartic acid) chain binding adriamycin.
Aspartic Acid↗
Purification of cone visual pigments from chicken retina.
A novel method for purification of chicken cone visual pigments was established by use of a 3-[(3-cholamidopropyl)dimethylammonio]-1- propanesulfonate-phosphatidylcholine (CHAPS-PC) mixture. Outer segment membranes isolated from chicken retinas were extracted with 0.75% CHAPS supplemented with 1.0 mg/mL phosphatidylcholine (CHAPS-PC system). After the extract was diluted to 0.6% CHAPS, it was loaded on a concanavalin A-Sepharose column. Elution from the column with different concentrations of methyl alpha-mannoside yielded three fractions: the first was composed of chicken violet, blue, and red in roughly equal amounts, the second predominantly contained chicken red, and the third was rhodopsin with a small amount of chicken green, which was separated from rhodopsin by DEAE-Sepharose column chromatography. Since CHAPS has little absorbance at both ultraviolet and visible regions, we could demonstrate the absolute absorption spectra of chicken red (92%) and rhodopsin (greater than 96%) in these regions. The maximum of the difference spectrum between either chicken red or rhodopsin and its photoproduct (all-trans-retinal oxime plus opsin) was determined to be 571 or 503 nm, respectively. Although chicken green was contaminated with a small amount of rhodopsin having a similar spectral shape, the maximum of its difference spectrum was located at 508 nm by taking advantage of the difference in susceptibility against hydroxylamine between these pigments. Although chicken blue and chicken violet were minor pigments present in the first fraction from the concanavalin A column, their maxima in the difference spectra were determined to be at 455 and 425 nm, respectively, by a partial bleaching method.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Regulatory activities of 2 beta-(3-hydroxypropoxy)-1 alpha, 25-dihydroxyvitamin D3, a novel synthetic vitamin D3 derivative, on calcium metabolism.
Regulatory activities of 2 beta-(3-hydroxypropoxy)-1 alpha, 25-dihydroxyvitamin D3 [ED-71], a novel synthetic vitamin D3 derivative, on calcium metabolism were investigated. The compound behaved similar to 1 alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3] in the ex vivo intestinal calcium transport using rat everted gut sac and the in vivo bone mobilization using vitamin D-deficient rats. By means of Raisz's assay method, 45Ca releasing activity of ED-71 was not greater than that of 1,25(OH)2D3. The time course curve of ED-71 in plasma made a mild round shape compared with that of 1,25(OH)2D3 and the former's plasma concentration remained increased longer than the latter's. The therapeutic effect of ED-71 for the animal models with osteoporosis seemed to be better than that of 1,25(OH)2D3. The results suggest that ED-71 may be a promising drug for therapy of osteoporosis.
Animals↗
Identification and determination of 1 alpha,25-dihydroxyvitamin D3 in rat skin by high-performance liquid chromatography and radioreceptor assay.
Endogenous 1 alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in normal rat skin was identified by using thermal isomerization to convert the metabolite into its pre-isomer, high-performance liquid chromatography (HPLC) and displacement potency with a chick intestinal cytosol receptor. When the metabolite in normal rat skin was determined by a radioreceptor assay after purification by Sep-Pak silica cartridge column chromatography and HPLC, the concentration was 71.0 +/- 6.6 pg/g of wet tissue (mean +/- S.D.). It is also shown that [3H]-1,25-(OH)2D3 and [3H]-25-hydroxyvitamin D3 administered intravenously in the mouse are located in the skin. These results suggest that the metabolite may play an important role in the skin.
Animals↗
Chicken red-sensitive cone visual pigment retains a binding domain for transducin.
Iodopsin (a red-sensitive cone visual pigment) and rhodopsin (a rod pigment) were isolated from chicken retina. They were separately reconstituted into phosphatidylcholine liposomes and then mixed with rod transducin (T alpha and T beta gamma) purified from bovine retina. Iodopsin enhanced, only when irradiated, the binding of GppNHp to T alpha to a similar extent to irradiated rhodopsin. Furthermore, the binding of GppNHp to T alpha in the presence of a photobleaching intermediate of iodopsin preferably required T beta gamma-2 rather than T beta gamma-1, which is very similar in profile to that in the presence of the intermediate of rhodopsin (J. Biol. Chem., in press). These results indicate that the binding domain for transducin in iodopsin should closely resemble that in rhodopsin.
Animals↗
Separation of B and T lymphocytes by a hybrid field-flow fractionation/adhesion chromatography technique.
A hybrid of the techniques of cellular adhesion chromatography and field-flow fractionation has been used for the effective separation of rat mesenteric B and T lymphocytes with nearly complete recovery of both cell species. Use of this hybrid technique also allows the relative binding strengths of cells to biomaterials and other surfaces to be rapidly and simply estimated. For the copolymer surface used here, B cells appear to bind with a force five times greater than T cells.
Animals↗
Antithrombogenic surfaces: characterization and bioactivity of surface immobilized PGE1-heparin conjugate.
A covalently bonded conjugate of commercial grade heparin and prostaglandin E1 (PGE1) was synthesized to prevent both fibrin formation and platelet aggregation during thrombus formation. The PGE1-heparin conjugate was immobilized on an imidazole carbamate derivatized sepharose bead surface through hydrophilic spacer groups (diamino-terminated polyethylene oxides). One end of the spacer group was coupled to the derivatized surface through a urethane bond between the amine group of the spacer and the derivatized surface. The free amine group of the immobilized spacers was coupled to a carboxylic group of the PGE1-heparin conjugate through an amide bond. Bioactivity of the immobilized conjugate (heparin activity) was measured in terms of increased clotting times (thrombin time assay) and for the inactivation of Factor Xa. Bioactivity of the immobilized compound (PGE1 activity) was analyzed by platelet adhesion and platelet release reactions using C14-5-hydroxytryptamine (5-HT). The conjugate immobilized via the C2 spacer showed the highest incidence of platelet adhesion, 5-HT released and the lowest activity for coagulation factors. In contrast, the 1000 and 4000 immobilized systems showed a significant reduction in platelet activation, while having the greatest effect on coagulation factors. The results of these experiments imply that the immobilized conjugate is active in preventing both pathways of thrombus formation, and the efficacy is improved through the use of long-chain hydrophilic spacer groups.
Alprostadil↗
In vitro and ex vivo platelet interactions with hydrophilic-hydrophobic poly(ethylene oxide)-polystyrene multiblock copolymers.
Hydrophilic-hydrophobic multiblock copolymers synthesized from telechelic oligomers of poly(ethylene oxide) (PEO) and polystyrene (PS) have been used to study the influence of hydrophilic and hydrophobic balance on interfacial interactions of these surfaces with blood components. In vitro coagulation assays show no inherent ability of these amphiphilic surfaces to affect contact activation or coagulation factors. In vitro platelet adhesion and release reactions from rabbit platelet-rich plasma were shown to be greatest on Biomer and PS homopolymer surfaces and least on cross-linked PEO surfaces, with the PEO-PS block copolymers demonstrating intermediate responses. These same substrates were tested in a new low-flow, low-shear arterio-artery shunt system in rabbits. Whole blood occlusion times were not a direct function of hydrophilic content as both PEO and PS homopolymers and Biomer showed short occlusion times, while PEO-PS block copolymers prolonged occlusion times considerably, depending on composition. Overall, results suggest that PEO-PS block copolymers promote unique whole blood responses in contrast to homopolymer and Biomer controls which are more complex than direct correlations to bulk hydrophilic and hydrophobic contents.
Anastomosis, Surgical↗
Human spleen cathepsin D: its characterization and localization in human spleen.
1. The cathepsin D was purified 1830-fold under mild conditions by a rapid procedure, based on two-step affinity chromatography. 2. Its molecular weight, amino acid composition and substrate specificity were shown to display minor differences from materials of other origins. 3. Inhibition with thiol compounds was found to be a specific phenomenon of the cathepsin D from the human spleen. 4. Production of antiserum specific for purified cathepsin D was demonstrated by immunodiffusion test, an immunoadsorbent column and immunoblotting of the crude enzyme in SDS gel. 5. In an immunocytochemical study, the antigenic sites for this enzyme were found to be localized in the reticuloendothelial system of the human spleen. 6. The role of this enzyme in human spleen cell was discussed.
Cathepsin D↗
Effects of ergocalciferol supplementation on the concentration of vitamin D and its metabolites in human milk.
The effect of maternal ergocalciferol (vitamin D2) supplementation on the concentrations of vitamin D, 25-hydroxyvitamin D (25-OH-D), 24R,25-dihydroxyvitamin D [24,25-(OH)2D], and 1 alpha,25-dihydroxyvitamin D [1,25-(OH)2D] in their milk was studied. Vitamin D2, D3, 25-OH-D2 and 25-OH-D3 were simultaneously determined by high performance liquid chromatography, and the determination of 24,25-(OH)2D and 1,25-(OH)2D was performed by competitive protein binding assay and radioreceptor assay, respectively, after separation of the D2 and D3 compounds. After healthy lactating mothers had received a daily oral dose of vitamin D2 (1,200 IU/d) for 4 wk, the concentrations of vitamin D2, D3 and the metabolites were determined in their plasma and milk. Although the plasma levels of 25-OH-D2 were significantly increased, the increase in milk was relatively small. On the other hand, the increase of vitamin D2 levels in milk was greater than that of 25-OH-D2 in milk after supplementation. The levels of 1,25-(OH)2D in milk was lower after 5 wk of lactation than after 1 wk of lactation, regardless of maternal vitamin D2 supplementation. When total antirachitic activities in milk were calculated, only a very slight increase was observed as a result of supplementation.
24,25-Dihydroxyvitamin D 3↗
Transport of cephalosporin antibiotics in rat renal basolateral membranes.
Transport mechanisms of cephalosporin antibiotics in rat renal basolateral membranes have been studied in isolated membrane vesicles. Uptake of [14C]p-aminohippurate, a typical organic anion, by basolateral membrane vesicles was enhanced when membrane vesicles were preloaded with unlabelled p-aminohippurate (counter-transport). Cephalosporins such as cephradine, cephalexin, and cefazolin inhibited the counter-transport of [14C]p-aminohippurate, as did unlabelled p-aminohippurate and probenecid. In contrast, cephalexin did not affect the uptake of [3H]tetraethylammonium, an organic cation, by basolateral membrane vesicles. These results suggest that most cephalosporins are transported via organic anion transport systems in rat renal basolateral membranes.
Animals↗
Bone marrow and serum concentrations of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1 alpha,25-dihydroxyvitamin D in patients with leukemia and normal subjects.
Concentrations of 25-hydroxyvitamin D (25-OH-D), 24,25-dihydroxyvitamin D [24,25(OH)2D], and 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] in bone marrow and serum of patients with leukemia and normal subjects were assayed. There were highly significant correlations between the bone marrow and serum concentrations of the respective vitamin D metabolites. Especially, the concentrations of 25-OH-D and 1,25(OH)2D in the bone marrow gave very similar values to those in serum. This is a big advantage in controlling the bone marrow levels of vitamin D metabolites in patients with leukemia, because doctors can calculate the bone marrow levels from the serum levels of the respective vitamin D metabolites without bone marrow aspiration. When 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) was administered orally to eight patients with leukemia, clinical conditions were improved in seven patients: four complete remissions (CR), one partial response (PR), and two minor responses (MR) without severe hypercalcemia. The results suggest that the therapy with 1 alpha-OH-D3 is fairly effective for curing human leukemia although it is not dramatic.
Adult↗
Concentrations of vitamin D-binding protein and vitamin D metabolites in plasma of patients with liver cirrhosis.
Plasma levels of vitamin D-binding protein (DBP) and vitamin D metabolites in patients with decompensated and compensated liver cirrhosis were assayed. Plasma levels of DBP in the decompensated group were significantly lower than those in the compensated group, but both were lower than the normal range. The plasma levels of 25-hydroxyvitamin D (25-OH-D) and 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] in the compensated group were within the respective normal ranges, whereas both values in the decompensated group were significantly lower than those in the compensated group. Most of 25-OH-D (higher than 96%) was confirmed to be circulated as a bound form with DBP in the plasma of not only the compensated but also the decompensated group. When vitamin D2 was given to the decompensated group, a significant increase of 1,25(OH)2D levels in the plasma could not be observed while 25-OH-D levels were increased. On the other hand, the administration of 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) to the decompensated group caused a significant increase in the plasma levels of 1,25(OH)2D. Therefore, we suggest that the administration of 1 alpha-OH-D3 is useful for the treatment of bone disease induced by liver cirrhosis.
Calcifediol↗
Changes in the concentrations of vitamin D and its metabolites in the plasma of healthy subjects orally given physiological doses of vitamin D2 by multivitamin or vitamin D preparations.
Changes in the concentrations of vitamin D and its metabolites in plasma of healthy subjects orally given physiological doses of vitamin D2 by multivitamin or vitamin D liquid preparations were determined and the bioavailability of vitamin D was studied. Separative assay on the D2 and D3 compounds of vitamin D, 25-hydroxyvitamin D (25-OH-D), 24R,25-dihydroxyvitamin D [24,25(OH)2D], and 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] was performed in plasma of eight healthy male volunteers. When the concentrations of vitamin D and its metabolites in plasma of volunteers were assayed after daily oral administration of 400 IU of vitamin D2 in a form of multivitamin tablet for 1 week, the variations of vitamin D3 and its metabolites in plasma levels were very small. In contrast, the concentrations of 25-OH-D2 and 1,25(OH)2D2 slightly increased after the administration, while neither vitamin D2 nor 24,25(OH)2D2 was detected. A single dose of 4,000 IU of vitamin D2 was orally given to the volunteers in a form of a vitamin D liquid preparation and the hourly variations were observed during 24 h. These concentrations of vitamin D2, 25-OH-D2, and 1,25(OH)2D2 were slightly higher than those of the repeated doses. The result suggests that even the high dose of 4,000 IU has little effect on the plasma levels of vitamin D2 and its metabolites by a single dose, indicating a low risk for hypervitaminosis D.
Administration, Oral↗
Protein-binding properties of 22-oxa-1 alpha,25-dihydroxyvitamin D3, a synthetic analogue of 1 alpha,25-dihydroxyvitamin D3.
Protein binding properties of 22-oxa-1 alpha,25-dihydroxyvitamin D3 (22-oxa-1,25-D3), a synthetic analogue of 1 alpha,25-dihydroxyvitamin D3 (1,25-D3), were compared with those of vitamin D3 derivatives. The order of binding affinity to the chick embryonic intestinal receptor was 1,25-D3 greater than 22-oxa-1,25-D3 greater than 25-hydroxyvitamin D3 (25-D3) greater than 24R, 25-dihydroxyvitamin D3 (24, 25-D3) greater than vitamin D3 (D3), while that to the rat plasma vitamin D-binding protein (DBP) was 25-D3 greater than 24,25-D3 greater than D3 greater than 1,25-D3 greater than 22-oxa-1,25-D3. The binding potencies of 22-oxa-1,25-D3 to the receptor and DBP were about 1/8 and 1/600 of the respective values of 1,25-D3. When the distribution of the tritiated compounds in human plasma components was examined by an in vitro polyacrylamide gel electrophoretic method, [3H]-22-oxa-1,25-D3 was found to bind only to the lipoproteins including chyromicron. These results suggest that the replacement of a carbon atom into an oxygen atom in the side chain structure of 1,25-D3 results significant decrease in the binding affinity to DBP and that 22-oxa-1,25-D3 is transported as a complex-form not with DBP but with lipoprotein to the target tissues.
Animals↗
[Recurrence and prognosis of renal pelvic and ureteral carcinoma].
Eighty-three patients with renal pelvic and ureteral carcinoma operated in Chiba University Hospital were followed. Age ranged between 23 and 79 years old (average 61.8 years) with the male-to-female ratio of approximately 2:1. Localization of tumors was in renal pelvis in 41 (49.4%), ureter in 29 (34.9%) and both in 13 (15.7%). Significant correlation in prognosis was obtained with macroscopic hematuria, histological classification, grade, stage and regional lymph node involvement. Recurrence was found on 49 cases (59%), 21 had intra-vesical tumor and 28 showed retroperitoneal recurrence or distant metastasis. In the former the mean tumor free interval was 14.8 months and 5 year survival rate was 62.1%. In the later the mean tumor free interval was 6.5 months and 3 year survival rate was 5%. 8 (38.1%) in 21 cases with low stage papillary transitional cell carcinoma showed recurrence and it was all intra-vesical tumor. 25 (56.8%) in 44 cases with high stage papillary transitional cell carcinoma showed recurrence. Retroperitoneal recurrence or distant metastasis was recognized in 12 cases. On the other hand 14 (87.5%) in 16 cases with non-papillary transitional cell carcinoma showed recurrence, which was all retroperitoneal recurrence or distant metastasis.
Adult↗