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Biomedical subjects

K Tsujikawa

Publications and source records attributed to K Tsujikawa.

At least 73 records · Page 4Linked to original sources

The inhibitory effect of bis[2-[(E)-2-octenoylamino]ethyl] disulfide on the cyclooxygenase pathway.

Bis[2-[(E)-2-octenoylamino]ethyl] disulfide (compd. I-3) inhibited collagen- and arachidonic acid-induced rat platelet aggregation, although not adenosine 5'-diphosphate (ADP)-induced rat platelet aggregation. Based on these results, we then investigated the inhibitory effect of compd. I-3 on thromboxane B2 formation from arachidonic acid in rat platelets, and prostaglandin I2 formation in rat aortae. Compound I-3 inhibited both thromboxane B2 and prostaglandin I2 formation, suggesting that it has an inhibitory effect on cyclooxygenase. The inhibitory effect of compd. I-3 was confirmed in experiments using a crude preparation of sheep seminal vesicle microsomal prostaglandin synthetase. These findings suggested that compd. I-3 has an inhibitory effect on cyclooxygenase activity, like nonsteroidal anti-inflammatory drugs.

Animals↗

Suppression of gastric ulcer induced by stress and HCL-ethanol by intravenously administered metallothionein-II.

A metallothionein isoform metallothionein-II was isolated from the livers of zinc acetate-treated rats. Metallothionein-II, which showed a single band on polyacrylamide gel electrophoresis, was subjected to two kinds of anti-ulcer screening systems. It was shown that intravenously administered metallothionein-II suppressed the formation of rat water-immersion stress- and HCl-ethanol-induced gastric ulcer significantly. The effect may partly be derived from the zinc contained in the metallothionein-II. However, the effect of metallothionein-II was much stronger than that of an equivalent mole of zinc. Apparently, metallothionein-II had an anti-ulcerogenic activity not based on the effect of intrinsic zinc.

Acetates↗

A mortality study of patients with Itai-itai disease.

A follow-up study was carried out from April 1967 to October 1982 on 117 patients with Itai-itai disease and 117 controls matched for age, sex, and residential area. The number of deaths during this period was significantly higher in the patients with Itai-itai disease (85, 72.6%) than in the controls (59, 50.4%). Comparison of the annual data from 1968 to 1982 showed that the number of deaths was significantly larger in the patient group. The mean survival time in years up to October 1982 was 76.4 in the patient group and 78.3 in the control group; the difference is statistically significant. These results show a long-lasting influence of Itai-itai disease on the prognosis of the patients.

Aged↗

Studies on pharmacological activation of human serum immunoglobulin G by chemical modification and active subfragments. IV. Induction of anti-inflammatory activity by chemical cleavage of interchain disulfide bonds in human immunoglobulin G and pharmacological activity of alkylated subfragments.

Commercially available human serum immunoglobulin G (IgG, native IgG) was separated into two fractions (Fr.I and II) using a diethylaminoethyl cellulose column. Heavy and light chains containing fractions were obtained from these two fractions after carboxamide-methylation. Thus, these fractions were subjected to an anti-inflammatory screening procedure and were shown to have a potent inhibitory activity against rat carrageenin induced paw edema, while no effect was observed in native IgG, Fr.I or II. The reduction and alkylation of the interchain disulfide bonds were essential to induce the anti-inflammatory activity. The anti-inflammatory activity of alkylated heavy and light chains of Fr.I (Fr.I-H and I-L) was also noted in subacute inflammation caused by the felt pellet and croton oil granuloma methods. Moreover, strong membrane stabilizing activities of Fr.I-H and I-L were demonstrated in vitro using rat red blood cell membrane and liver lysosomal membrane.

Alkylation↗

Studies on pharmacological activation of human serum IgG by chemical modification and active subfragments. V. Mechanism of anti-inflammatory action of carboxamide-methylated L-chain (Fr. I-L) and H-chain (Fr. I-H) from human serum IgG.

Using the xylene ear method in mice, it was demonstrated that the reduced and carboxamide-methylated fragments of human serum IgG (Fr. I-H and Fr. I-L) significantly suppressed capillary permeability. It was also shown that leucocyte emigration and protein leakage into and esterase activity of the pouch fluid, which was accumulated by carboxy-methyl cellulose injections, were suppressed by the administration of the fragments. Moreover, the lipid peroxide level was lowered by both Fr. I-H and Fr. I-L in the liver of either carrageenin-induced, paw edema-bearing or kaolin pouch inflammation in rats. The facts obtained in this study indicated the mechanisms of the anti-inflammatory effects of Fr. I-H and Fr. I-L were mainly caused by both the inhibitory effect on leucocyte emigration into the site of injury and stabilization of the membrane by inhibiting lipid peroxidation of the inflammatory tissue.

Acid Phosphatase↗

Na-K ATPase activity of erythrocyte membrane correlated with urinary Na/K ratio in normotensive adolescents with a family history of hypertension.

In female adolescents with a normal blood pressure range, the correlation between urinary sodium excretion and Na-K ATPase activity of erythrocyte membrane was investigated. 34 subjects with a family history of hypertension showed a significantly positive correlation between body mass index and mean blood pressure (r = 0.64, p less than 0.01), and a significantly lower urinary Na/Cr and Na/K ratio compared with 37 subjects without the same family history (p less than 0.05 and p less than 0.01, respectively). The positive correlation between urinary Na/K ratio and Na-K ATPase activity of erythrocyte membrane was demonstrated in only subjects with a family history of hypertension (r = 0.41, p less than 0.05). The authors discuss these significant correlations in terms of the abnormal membrane cation fluxes associated with essential hypertension.

Adolescent↗

[Mortality of silicosis patients among migrant workers].

Migrant workers known in Japanese as "dekasegi" refer to workers who migrate seasonally from their town of residence to areas where work is readily available. The eastern part of Toyama Prefecture is well known as a source of migrant workers who engage in jobs associated with dust exposure such as tunnel projects. Most of these workers suffered from silicosis. A total of 695 migrant workers suffering from silicosis who had underwent health screening between 1977 and 1982 were followed until the end of 1983. For cases of death, the cause and date of death were individually confirmed on the basis of death certificates. Based on these data, the person-years of risk and cause-specific mortality rates were calculated. The mean person-years of risk per person was 4.7. During this period of observation, there were 75 deaths among these silicosis patients, giving a mortality rate of 23.0 per 1,000 person-years of risk. When classified by the Japanese roentgenographic category of pneumoconiosis, the mortality rate was 10.5 for category 1, 21.3 for category 2, 38.6 for category 3 and 49.3 for category 4. The mortality rates of categories 3 and 4 were significantly higher than those of categories 1 and 2. The highest cause-specific mortality rate among silicosis patients per 1,000 person-years was 5.2 for malignant neoplasms followed by 3.7 for pulmonary tuberculosis, 3.1 for both cardiovascular diseases and pneumoconiosis, and 2.8 for pneumonia and bronchitis. High mortality rates in the 50-69 age group were found among silicosis patients belonging to categories 3 and 4. By cause of death, the mortality rates of all malignant neoplasms (especially lung cancer), pulmonary tuberculosis, and cerebrovascular diseases were relatively high in this age group. In the 70-89 age group, the mortality rate of those belonging to categories 2, 3 and 4 was high and by cause of death the mortality rates of pneumoconiosis, pulmonary tuberculosis, all malignant neoplasms (especially lung cancer), cardiovascular diseases and pneumonia and bronchitis were high. The mortality rates of silicosis patients with abnormal findings in %VC, FEV1% and AaDO2 by pulmonary function tests tended to be higher than those of silicosis patients without such abnormalities.

Adult↗

Purification and characterization of a fish lectin from the external mucus of ophidiidae, Genypterus blacodes.

A lectin was isolated from the external mucus of fish, Genypterus blacodes. This is the first lectin isolated from fish. The molecular weight of the lectin, determined by gel filtration, was approximately 32 000, whereas 8 000 was indicated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence of 2-mercaptoethanol. Amino acid analysis demonstrated that the lectin contained large amounts (near 30% of the residues) of lysine, but no tryptophan. The lectin agglutinated mouse, rabbit and human erythrocytes at a concentration of 15.6 micrograms/ml. An inhibition test revealed that the lectin was strongly inhibited by N-acetyl-glucosamine, mucin and orosomucoid. Binding studies performed with iodinated asialo-orosomucoid indicated that the lectin contained a high affinity binding site with a dissociation constant of 1.1 X 10(-8) M. The lectin required the presence of calcium ion for both its hemagglutination and binding activity.

Amino Acids↗

Studies on pharmacological activation of human serum immunoglobulin G by chemical modification and active subfragments. III. Mechanism of anti-ulcerous action of alkylated light chain (Fr. I-L).

The effects of a new anti-ulcer agent Fr. I-L, a reduced and carboxamide-methylated light chain of human immunoglobulin G, on defensive factors in gastric mucosa were studied. Fr. I-L increased the mucopolysaccharide contents (hexosamine, uronic and sialic acids) in the gastric mucosa of intact rats and inhibited the decrease of mucopolysaccharide contents in the gastric mucosa of rats with phenylbutazone-induced gastric ulcers. The activation of the biosynthesis of mucopolysaccharides by Fr. I-L was suggested by tracing the incorporation of 35SO4(2-) into the gastric mucosa. The administration of aspirin or phenylbutazone caused an increase of mucopolysaccharase activity in the gastric mucosa and the concomitant administration of Fr. I-L blocked the elevation of the enzyme activities. Fr. I-L also showed inhibitory activities on the local fibrinolysis and lipid peroxidation in the gastric mucosa.

Animals↗

Mitogenic activity and in vitro fertilization inhibitory activity of Genypterus blacodes lectin.

A lectin which we purified from the mucous of Ophidiidae Genypterus blacodes showed a potent mitogenic activity which was comparable to that of concanavalin A (con A). On the other hand, the lectin treated with 2-mercaptoethanol showed an anti-mitogenic activity against con A and lipopolysaccharide (LPS). Lymphocytes were separated into a T cell rich fraction and B cell rich fraction by soybean agglutinin. The mitogenic activity of G. blacodes lectin was examined using these cells. It was suggested that the mitogenic activity of G. blacodes lectin was based on the stimulation of T cells. The lectin was also subjected to both the sperm agglutination and the in vitro fertilization tests in mouse. It was demonstrated that: a) the lectin receptors were ubiquitous on sperm; b) in vitro fertilization of mouse ova was completely blocked by the binding of the lectin to the zona pellucida of the ova.

Animals↗

Studies on pharmacological activation of human serum IgG by chemical modification and active subfragments. II. Inhibitory effects of carboxamide-methylated L chain from human serum IgG on various ulcer models and its inhibition mechanism.

In view of the strong inhibitory effects of the carboxamide-methylated L chain (Fr. I-L) from human IgG on gastric ulceration and juice secretion, we carried out various experiments to clarify the mechanism of its action and obtained the following results. Fr. I-L inhibited the gastric ulceration induced by phenylbutazone or aspirin in rats, but no appreciable effect was observed on stress or acetic acid ulceration. The distribution of 14C-labelled Fr. I-L increased particularly in the stomach mucous membrane of rats after the intravenous or intraperitoneal administration. The hexosamine content in the gastric mucous membrane, reduced by the treatment with phenylbutazone, aspirin or pylorus-ligation, was recovered by the administration of Fr. I-L to an intact level. The high total of hexosamine levels found in the gastric juice after aspirin treatment or pylorus-ligation were decreased by the injection of Fr. I-L or cimetidine. The histochemical observation revealed that the concomitant administration of Fr. I-L with phenylbutazone or aspirin prevented the abolishment of Hematoxylin-Eosin, Periodic Acid Schiff and Alcian Blue staining polysaccharides from the stomach epithelial cells.

Animals↗