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Biomedical subjects

H Takada

Publications and source records attributed to H Takada.

At least 343 records · Page 19Linked to original sources
PubMed1986

Inhibitory effect of dietary selenium on carcinogenesis in rat glandular stomach induced by N-methyl-N'-nitro-N-nitrosoguanidine.

The influence of dietary selenium on the incidence of stomach carcinoma induced by N-methyl-N'-nitro-N-nitrosoguanidine was studied in 108 rats that survived for over 10 wk. The incidence of glandular stomach cancer in the high-selenium (4.0 ppm) diet group (20 carcinomas in 54 rats) was lower than in the low-selenium (0.1 ppm) diet group (33 carcinomas in 54 rats). The selenium level and glutathione peroxidase activity in the blood, liver, and stomach mucosa were significantly higher in the high-selenium diet group than in the low-selenium diet group. Glutathione peroxidase activity as well as the concentration of selenium in the glandular stomach was increased significantly in the high-selenium diet group.

Adenocarcinoma↗
PubMed1986

Effects of dietary saturated and unsaturated fatty acids on fecal bile acids and colon carcinogenesis induced by azoxymethane in rats.

To determine whether the kind of dietary fat affects colon carcinogenesis, male Donryu rats were fed a 5% fat diet containing linoleate, an unsaturated fat, or stearate, a saturated fat, in semipurified fat-free chow. The rats were given azoxymethane (7.4 mg/kg body weight) s.c. once a week for 11 weeks and killed 15 weeks after the last injection of the carcinogen. The rats on the unsaturated fat diet had a significantly higher incidence of colon tumors. Fatty acid analysis of cholesterol esters in the liver and examination of the amount of fecal bile acids showed that the unsaturated fat diet increased the level of cholesterol linoleate and arachidonate in the liver and also increased the fecal excretion of bile acids, especially that of lithocholic acid. The colon tumors in rats on the unsaturated fat diet, compared with those in rats on the saturated fat diet, contained a higher level of lysophosphatidylcholine. These results suggest that increased fecal excretion of bile acids due to increased polyunsaturated cholesterol esters in the liver stimulates phospholipase A2 activity of colon initiated cells and enhances colon carcinogenesis in rats on the unsaturated fat diet.

Animals↗
PubMed1985

In vitro antigenic reactivity of synthetic lipid A analogues as determined by monoclonal and conventional antibodies.

Cross-reactivities of synthetic lipid A analogues with monoclonal and conventional antibodies against Salmonella lipid A were studied. It was shown that the in vitro antigenicity of a synthetic compound 506, beta-(1----6) D-glucosamine disaccharide 1,4'-bisphosphate, which is acylated at 2'-amino and 3'-hydroxyl groups with (R)-3-dodecanoyloxytetradecanoyl and (R)-3-tetradecanoyloxytetradecanoyl groups, respectively, and has (R)-3-hydroxytetradecanoyl groups at 2-amino and 3-hydroxyl groups, was practically indistinguishable from that of the natural E. coli lipid A preparation, and that both phosphates in positions 1 and 4' as well as ester- and amide-linked fatty acyl residues, particularly 3-acyloxyacyl group, of the glucosamine disaccharide are involved in the cross-reactivity of lipid A as important antigenic determinants.

Animals↗
PubMed1985

The antitumor effects of human lymphoblastoid interferon on human renal cell carcinoma in athymic nude mice.

The antitumor effects of human lymphoblastoid interferon (HLBI) on human renal cell carcinomas transplanted in nude mice, i.e., KU-2 and RCC-1, were investigated and compared with those on other human tumors, viz. HeLa (cervical carcinoma), KB (nasopharyngeal carcinoma), H.Ep#2 (laryngeal carcinoma), and MX-1 (breast cancer). A pharmacokinetic study on HLBI was also carried out in non-tumor-bearing nude mice. HLBI therapy was performed with a dose of 10(5) IU/mouse by daily SC or IT (intratumoral) injection for 2-4 weeks. Two renal cell carcinomas, KU-2 and RCC-1, proved to be highly sensitive to HLBI. The growth of these tumors was inhibited not only by IT but also by SC injection of HLBI. In contrast, HLBI exerted only a slight effect or none at all on the other human tumors, namely, MX-1, KB, H.Ep#2, and HeLa, even when given by IT injection. The data show that the antitumor effects of HLBI depend on the types of human tumors and may be relevant to the clinical observation that renal tumors are sensitive to HLBI. The serum HLBI reached a peak level of 4,390 U/ml 1 h after a single SC injection at a dose of 10(5) IU/mouse and declined with a half-life of 4 h to 128 U/ml 24 h later. This time-course was not affected by 10 consecutive daily injections of HLBI. In nude mice, the consecutive administration of HLBI at this dose level appears to result in neither accumulation nor rapid clearance due to antibody formation. From this range of serum HLBI levels and its in vitro anticellular activity, the in vivo antitumor effects of HLBI in nude mice seemed to depend on its direct anticellular action.

Animals↗
PubMed1985

Echocardiographic assessment of left ventricular wall motion in myocarditis.

Segmental wall motion abnormalities are common in patients with myocarditis. Left ventricular (LV) regional wall motion was assessed in six patients with myocarditis by two-dimensional echocardiography. Some of our patients demonstrated regional thinning of the wall, similar to myocardial infarction. Therefore, segmental wall motion abnormalities with or without regional wall thinning detected by two-dimensional echocardiography cannot be used to differentiate myocarditis from coronary artery disease. Nevertheless, echocardiography can be performed repeatedly and is useful for evaluating the severity of myocarditis by assessing LV regional wall motion abnormalities, changes in LV wall thickness and cardiac pump function during the course of the disease.

Adult↗
PubMed1985

Enhancement of dengue virus infection in cultured mouse macrophages by lipophilic derivatives of muramyl peptides.

Dengue virus multiplication in cultures of a murine myelomonocytic cell line (WEHI-3) as well as mouse peritoneal macrophages was enhanced by treatment of the cells with lipophilic derivatives of muramyl peptides for 2 or 3 days before virus inoculation, but not for 2 hr before virus inoculation or during the adsorption period. The infection-enhancing activity of the materials was dependent on their chemical structure, correlating with their immunoadjuvanticity. The infection enhancement in WEHI-3 cells was due primarily to an increase in the number of virus-infected cells which was accompanied by an increased cellular capacity to bind latex particles to their cell surfaces.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Immunopharmacological activities of a synthetic counterpart of a biosynthetic lipid A precursor molecule and of its analogs.

Synthetic lipid A analogs (compounds 404 through 406) were examined for their immunopharmacological activities. These compounds had two amide-bound and two ester-bound (R)-3-hydroxytetradecanoyl groups at the C-2 and C-2' and the C-3 and C-3' positions, respectively, of beta (1-3)glucosamine disaccharide. In all of the in vitro assays, these synthetic compounds exhibited high activities comparable to those of a reference lipid A prepared from Escherichia coli O8:K27 Re-mutant strain F515. The compounds activated the clotting enzyme cascade of the horseshoe crab, activated the human complement via the classical pathway, caused polyclonal B-cell activation, stimulated the phagocytosis of sheep erythrocytes by murine peritoneal macrophages, and enhanced the migration of human polymorphonuclear leukocytes. They also increased the thymidine uptake of splenocytes of BALB/c nu/nu and C3H/HeN mice but not those of C3H/HeJ (a nonresponder to lipopolysaccharide). A dephosphorylated derivative, compound 403, was barely active in all of the above assays except for the enhancement of polymorphonuclear leukocyte migration. However, compounds 404 through 406 were feeble in pyrogenicity and could not prepare the local Shwartzman reaction, although they were very lethal to galactosamine-loaded mice. Therefore, synthetic lipid A analogs described here were fully immunopharmacologically active in in vitro assays, but all of them were far less active than natural E. coli F515 lipid A regarding the biological activities characteristic of endotoxic lipopolysaccharides and lipid A's. The high lethal toxicity of compound 406 (1,4'-bisphosphate) to the galactosamine-loaded mice may not reflect its real toxicity to normal mice. In all activities examined, compound 406 was quite comparable to a biosynthetic lipid A precursor, a natural counterpart of compound 406. The immunopharmacological activities of these newly synthesized lipid A analogs, especially compound 406, were much stronger than those of compounds that had been synthesized earlier by using the originally proposed model of the lipid A structure. The findings described in this report justify the acylation pattern of a disaccharide backbone of lipid A, revised on the basis of recent analytical studies. The low in vivo endotoxic activities of the present lipid A analogs are most probably due to the fact that the kinds of acyl groups were different from those of the complete lipid A from E. coli, although there were no differences in the acylation positions on the disaccharide backbone.

Adjuvants, Immunologic↗
PubMed1985

Synthetic lipid A with endotoxic and related biological activities comparable to those of a natural lipid A from an Escherichia coli re-mutant.

A synthetic compound (506), beta (1-6) D-glucosamine disaccharide 1,4'-bisphosphate, which is acylated at 2'-amino and 3'-hydroxyl groups with (R)-3-dodecanoyloxytetradecanoyl and (R)-3-tetradecanoyloxytetradecanoyl groups, respectively, and has (R)-3-hydroxytetradecanoyl groups at 2-amino and 3-hydroxyl groups, exhibited full endotoxic activities identical to or sometimes stronger than those of a reference lipid A from an Escherichia coli Re-mutant (strain F515). Endotoxic activities tested include pyrogenicity and leukopenia-inducing activity in rabbits, body weight-decreasing toxicity in normal mice, lethal toxicity in galactosamine-sensitized mice and chicken embryos, and the preparation and provocation of the local Shwartzman reaction in rabbits. Compound 406, a synthetic counterpart of a biosynthetic precursor of lipid A molecule, showed by contrast only weak activities in all of the above assay systems except for the lethality in galactosamine-loaded mice. This finding strongly suggests that the presence of acyloxyacyl groups at the C-2' and C-3' positions of the disaccharide backbone is one of the most important determinant structures of the lipid A molecule for exhibition of strong biological activities characteristic of lipopolysaccharide and its lipid A moiety. The activities of the corresponding 4'-monophosphate (compound 504) and 1-monophosphate (505) analogs were considerably less than those of the parent molecule 506 and the reference F515 lipid A. Regarding other biological activities, not only compound 506 but also compounds 504, 505, and 406 showed definite activities, sometimes comparable to those of F515 lipid A and other reference natural products. These are the activation of Tachypleus tridentatus amoebocyte clotting enzyme cascade and human complement via the classical pathway, mitogenic and polyclonal B-cell activation of murine splenocytes, stimulation of peritoneal macrophages in a guinea pig, enhancement of migration of human blood polymorphonuclear leukocytes, and induction of a serum factor that is cytostatic and cytocidal to L-929 cells in Mycobacterium bovis BCG-primed mice. Relative potencies of test synthetic compounds depended on the assay systems and varied from one system to another. Dephospho-compound 503 lacked most of the biological activities that were definitely observed with phosphorylated compounds, probably because of its insolubility. This study demonstrates the successful chemical synthesis of an E. coli-type lipid A.

Adjuvants, Immunologic↗
PubMed1985

Rats with congenital tremor and curled whiskers and hair.

In a colony of Kyo: Wistar strain of rats, we found animals with curled whiskers and hair. These rats exhibited tremor when they moved. There were no sex differences in phenotype and behavior, and the affected animals of both sexes were sterile. Among pairs that produced at least one tremulous offspring, 21.8% of the females and 21.7% of the males were affected; these proportions suggest that the anomaly is caused by an autosomal recessive gene. When the presumed heterozygous males were crossed with WAG/Rij females, about half of their female F1 hybrids were heterozygous, and they produced 26.1% (43/165) of the affected offspring when backcrossed to the sires. Again these results suggested that the disorder is caused by an autosomal recessive gene. We tentatively designated the gene as tremor (tm). The main pathological changes were seen in the gonad and central nervous system. The gonads of both sexes were aplastic even in adult animals. Vacuole formation was seen widely in the central nervous system and sometimes exhibited a spongy appearance. After administration of alpha-methyl-p-tyrosine, the norepinephrine content of the cerebellum was high, indicating that some anomalies of catecholamine release were present. The mutation is being maintained by random mating of the littermates of affected animals. Detailed pathological, endocrinological, neuropharmacological, and genetical studies are proceeding.

Animals↗
PubMed1985

[Clinical evaluation of cefmenoxime (CMX) for complicated urinary tract infection].

Cefmenoxime (CMX), a new semisynthetic antibiotic, was administrated in 29 cases diagnosed as complicated urinary tract infection. All patients received drip injection of 2 g (twice a day) for 5 days. Clinical results were excellent in 1 patient (3.4%), good in 15 patients (51.8%) and poor in 13 patients (44.8%). Effectiveness rate was 55.2%. In bacteriological response, out of 35 strains 27 (77.1%) strains were eradicated and 8 (22.9%) strains persisted. As for side effects, except one case of transient diarrhea after administration, no noteworthy reactions were observed. Laboratory abnormalities attributed to CMX treatment consisted of 4 cases of elevated serum transaminase and 2 cases of elevated serum creatinine.

Adult↗
PubMed1984

Immunobiologically active lipid A analogs synthesized according to a revised structural model of natural lipid A.

Synthetic lipid A analogs which have two amide-bound and two ester-bound (R)-3-hydroxytetradecanoyl groups at the C-2 and -2' and C-3 and -3' positions of beta(1-6)glucosamine disaccharide mono- or diphosphates showed high activities in most in vitro assays, and the lethality of a diphosphate derivative to galactosamine-treated mice was almost comparable to that of natural lipid A. The pyrogenicity and Shwartzman induction activity of the synthetic analogs, however, were much less than those of natural lipid A.

Adult↗