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Biomedical subjects

Y Yoshioka

Publications and source records attributed to Y Yoshioka.

At least 163 records · Page 9Linked to original sources

CV-3988 - a specific antagonist of platelet activating factor (PAF).

CV-3988, rac-3-(N-n-octadecylcarbamoyloxy)-2-methoxypropyl 2-thiazolioethyl phosphate was shown to be a specific inhibitor of platelet activating factor (PAF). This compound in concentrations of 3 x 10(-6) to 3 x 10(-5)M inhibited aggregation of rabbit platelets induced by PAF (3 x 10(-8)M), while it had no effect on the aggregation induced by arachidonic acid, ADP, collagen or A-23187. CV-3988 alone even at a concentration of 10(-3)M had no effect on platelet aggregation. The inhibitory action of CV-3988 on the PAF-induced aggregation was independent of the formation of micelles. The PAF (0.1 to 1.0 micrograms/kg, i.v.)-induced hypotension in anesthetized rats was also inhibited dose-dependently by the i.v. administration of CV-3988 (1 and 10 mg/kg), while the hypotensive actions induced by the i.v. administration of acetylcholine (1 micrograms/kg), arachidonic acid (1 mg/kg), bradykinin (10 micrograms/kg), isoproterenol (1 microgram/kg) and histamine (100 micrograms/kg) were not altered by CV-3988 (10 mg/kg, i.v.). All these findings indicate that CV-3988 specifically inhibits the action of PAF in vitro and in vivo. This is the first report of a PAF antagonist which can specifically inhibit the PAF-induced hypotension as well as the PAF-induced platelet aggregation.

Adenosine Diphosphate↗

Antitumor activity of tetrahydro-2-furanyl- and tetrahydro-2-pyranyl-glucans obtained by chemical modification of (1 leads to 3)-beta-D-glucan from Alcaligenes faecalis var. myxogenes IFO 13140 and its lower molecular weight glucans.

The well-defined (1 leads to 3)-beta-D-glucan with DP (degree of polymerization) 540 and the various chain-length (1 leads to 3)-beta-D-glucans prepared by its hydrolysis were chemically modified to furanyl- and pyranyl-derivatives. As a primary screening, the effect of 20 derivatives thus obtained was tested on Sarcoma 180 solid tumor transplanted sc into allogeneic ICR mice; the dose was 10 mg/kg ip for 10 days. Eleven derivatives that showed a strong antitumor effect on Sarcoma 180 were also tested on Meth-A solid tumor in syngeneic mice. Of the derivatives tested, five furanyl-derivatives (F-4, F-6, F-7, F-10, and F-11) and one pyranyl-derivative (P-5) had potent antitumor effects on this syngeneic tumor system at ip doses of 10 or 30 mg/kg for 10 days. By oral administration, only two derivatives (F-10 and P-3) showed moderate antitumor activity against Sarcoma 180, without complete tumor regression. The mechanism of action of these derivatives was considered to be host-mediated and similar to that of the original glucan, because of a lack of effect in vitro.

Alcaligenes↗

Experimental study on immunological reactions against the articular cartilage.

In rats immunized with articular cartilage antigens, delayed hypersensitivity was detected by the macrophage migration inhibition test and delayed footpad reaction. Additionally, a proliferative response was found in the regional lymph nodes of immunized rats. The mixed addition of sensitized lymphocytes and antibodies exerted a cytotoxic effect on cultured chondrocytes. Articular damage including accelerated chondrolysis may have some relation to delayed hypersensitivity to autologous articular cartilage antigens.

Animals↗

Studies on antitumor polysaccharides of Flammulina velutipes (Curt. ex Fr.) Sing.II. The structure of EA3 and further purification of EA5.

An antitumor polysaccharide, EA3 isolated from a Japanese edible mushroom, Flammulina velutipes (CURT. ex FR.) SING. is composed of D-glucose. Studies to determine its structure were performed by mean of partial acid hydrolysis, acetolysis and the chemical analysis of the complete hydrolysates of the fully methylated polysaccharide. Thus the chemical structure of EA3 was found to be that of a beta-(1 leads to 3)-glucan. Another antitumor polysaccharide (EA5) also isolated from F. velutipes was fractionated on a concanavalin A-Sepharose 4B column. The active antitumor component was further purified by column chromatography on Sephadex G-200. Among the polysaccharides isolated the highest molecular weight polysaccharide (EA501) showed the highest rate of antitumor activity. The component sugar of EA501 were found to be D-glucose 42.3%, D-galactose 17.3%, D-mannose 12.2%, D-xylose 6.7% and L-arabinose 14.7%.

Agaricales↗

Functional abnormalities of hemoglobin Toyoake (142 (H20)beta, Ala leads to Pro).

Oxygen equilibrium of Hb Toyoake (142 (H20)beta, Ala leads to Pro) is characterized by an oxygen affinity 6-times higher than that of Hb A, a slightly decreased alkaline Bohr effect, diminished cooperativity, with Hill's coefficient decreased by 1.2, and reduced response to 2,3-diphosphoglycerate and inositol hexaphosphate. These properties are in qualitative agreement with those shown previously from oxygen equilibrium data for hemolysate containing Hb Toyoake. The heat of oxygenation was -13.5 kcal/mol for Hb Toyoake and -12.9 kcal/mol for Hb A at pH 7.4 in 0.1 M Cl- and they became equal when corrected for the heat of oxygen-linked proton and Cl- release. OxyHb Toyoake autooxidized faster than oxyHb A. The visible absorption spectrum and electron paramagnetic resonance spectrum of oxidized Hb Toyake indicated that oxidation of this hemoglobin, either by autooxidation or by K3Fe(CN)6, is followed by gradual conversion into hemichrome derivatives. The soret peak of deoxyHb Toyoake was lowered compared to that of deoxyHb A and the magnitude of narrow-banded oxy-minus-deoxy difference spectrum around 290 nm was smaller for Hb Toyoake than for Hb A, indicating that the former remains predominantly in the R state upon deoxygenation. The functional abnormalities, including tendency to lose heme groups previously reported, were interpreted in terms of structural disturbance by proline at 142beta of 141 leucine, 143 histidine, 145 tyrosine, and 146 histidine residues of the same beta chain.

Diphosphoglyceric Acids↗

[A study on the stress analysis of the pelvis by means of the three-dimensional photoelastic experiments (author's transl)].

The processes are as follows: 1) Life-sized photoelastic models molded from a cadaver pelvis are made of Epoxy resin. 2) In order to practice the stress freezing process, the models are set to our original loading apparatus in the electric heater. The forces exerted on the hip models are both body weight and four kinds of muscular forces, those of the abductor, adductor, rectus femoris and gluteus maximus. 3) After the stresses are frozen in the models, they are cut off into slices to observe isochromatic and isoclinic lines. 4) In the stress analysis both the shear difference method and the double slice method are utilized to obtain more accurate stress distributions. And the results have been summarized as follows: 1) In the ring-shaped slices large stresses are observed especially at four areas; namely the central area of the iliac bone, the acetabulum proximal to the ilium, the pubic ramus and the area adjacent to the sacroiliac joint. The specific areas where hydrostatic pressure works are seen at two points in the deep acetabular cavity. 2) The principal stress lines of almost all slices tend to flow smoothly and monotonously along the ilium, the sacrum and the pubic bone, but as they approach the acetabulum they run in complex patterns and make some singular points. 3) Around the acetabulum the principal stress lines of one group run in concentric circles and those of the other group radiate in all directions from the center of the acetabulum at the upper half of the dome which supports the load. The stress here was 5 to 6 times greater than in the lower half of the dome. 4) The acetabulum is stretched vertically and deformed into an oval shape. The horse shoe-shaped articular facet is deformed as both beaks approach each other. 5) As for the slices of the pelvic ring the normal acetabulum tends to be obviously deformed as it holds or embraces the femoral head. As a result of this deformity the stability between the acetabulum and the head increases. On the other hand the dysplastic acetabulum shows none of those phenomena. 6) The iliac bone of the pelvic ring is deformed into the "S" shape and the pubic ramus the "C" shape, the "S" shape, or the "Z" shape depending on the limb position. The pelvic ring tends to be deformed into a heart shape during abduction.

Acetabulum↗

Nonsteroidal antiinflammatory agents. 2. Derivatives/analogues of dibenz[b,e]oxepin-3-acetic acid.

6,11-Dhydro-11-oxodibenz[b,e]oxepins and some related compounds have been synthesized and evaluated for antiinflammatory effect according to the carrageenan paw edema method in rats. The structure-activity relationships have been discussed among acetic acid, carboxylic acid, alcohol, and tetrazole derivatives of dibenzoxepins and acetic acid derivatives of thienobenzoxepins and of the corresponding thiepins. The 3-isopropyl alcohol 9 and 11-deoxo-3-propionic acid (49) were more active than indomethacin but not as active as the title compound (i.e., 43). Carboxylic acids, tetrazoles, esters, amides, and ketones were less active than the corresponding acetic acids. Three compounds (31, 33, and 34) were evaluated for ulcerogenicity and lethality but none surpassed 6,11-dihydro-11-oxodibenz[b,e]oxepin-3-acetic acid (41) in therapeutic ratio.

Animals↗

A two-dimensional echoaortocardiographic approach to dissecting aneurysms of the aorta to prevent false-positive diagnoses.

Two patients with dissecting aneurysms of the aorta of Debakey type I and II, 10 healthy subjects, and 2 patients with signs mimicking aortic-root dissection were studied by two-dimensional echoaortocardiography, standard echocardiography, and M-mode scanning. In both electrocardiographically gated and nonelectrocardiographically gated two-dimensional echoaortocardiograms of each patient, aortic-root dissections were clearly visualized. Because of the possibility of a false-positive diagnosis of an aortic-root dissection by previously reported criteria (including cases in the authors' experience and in the literature), the authors are convinced that the combination of two-dimensional and standard echoaortocardiography provides the most reliable echo diagnosis of this disease.

Adult↗

Breeding of cynomolgus monkeys through successive generations by indoor cage system.

Vital statistics on the breeding through successive generations were presented for the cynomolgus monkey colony of NIH, Tokyo. The results of this retrospective survey clearly demonstrated the third (F2) and the fourth (F3) generations could be bred and reared successfully by the indoor caged-breeding system in which either individual timed-mating or group mating procedure was adopted. Several important and difficult problems involved in the production of successive generations of the cynomolgus monkey by our breeding system were discussed from the standpoint of laboratory animal science.

Age Factors↗