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Biomedical subjects

H Imai

Publications and source records attributed to H Imai.

At least 577 records · Page 32Linked to original sources

Intratumor immunochemotherapy with 5-fluorouracil emulsion and BCG in C3H/HE mice transplanted with MH134.

Responses to intratumor immunochemotherapy by intralesional injections of BCG and 5-fluorouracil (5-FU) emulsion, prior to resection of a transplanted primary tumor, were investigated using a host-tumor system consisting of C3H/He mice and MH134. A significant prolongation of survival and suppression of lymph node metastasis were attained by the combined use of BCG and 5-FU emulsion, compared to treatment with either BCG or 5-FU emulsion alone. However, this did not alter the survival rate of the combined regimen group as compared with those of the latter treatment groups. When rechallenged with the same tumor cells after resection of the primary lesion, mice treated with BCG alone exhibited a marked tumor growth suppression while the control and BCG + 5-FU emulsion group showed a less effective suppression. No such effects were observed in the group given 5-FU emulsion alone. Assessment by the splenic plaque-forming cell assay with sheep erythrocytes revealed a marked inhibition in the development of humoral immunity in the animals treated with 5-FU emulsion alone. Concomitant administration of BCG was effective to some extent in preventing the depression of these immune functions. The data obtained indicate that the clinical response to immunochemotherapy is determined by a balance between the antitumor effect of the antitumor agent administered and its influence on the host's immune functions.

Animals↗

[Experimental study on local immunochemotherapy].

The purposes of this work were twofold: firstly to determine whether intratumor chemoimmunotherapy was more effective than either treatment alone or systemic therapy and; secondly to study how the intratumor therapy affected on the development of the tumor-specific immunity. Inbred male C3H/He mice and mouse ascited hepatoma 134 (MH 134) of C3H origin were used as host-tumor system. Mitomycin C was used as the chemotherapeutic agent and BCG as the immunopotentiating agent. Intratumor treatment of MMC + BCG led to complete cure in 85 percent of the mice. The lymph node metastases were markedly inhibited in the group treated with MMC + BCG compared to the groups treated with MMC alone or BCG alone. The growth of rechallenged tumor was investigated; 79% of mice treated with MMC + BCG were immune to rechallenge, whereas 57% of mice treated with BCG alone. The number of PFC and DTH against SRBC of the mice treated with MMC intraperitoneally significantly decreased compared to that treated with MMC intratumorally.

Animals↗

Evans blue dye: its accumulation in extracellular space in relation to endothelial cell basement membrane in normal an atherosclerotic areas of abdominal aorta.

Intravenously (IV) injected Evans blue dye consistently accumulates at particular areas in aortas of normal swine. Theses areas are also where IV injected tracer cholesterol accumulates. We studied the ultrastructural characteristics of blue vs nonblue areas in the abdominal aortas of both control and atherosclerotic swine. In blue areas, the basement membrane was largely missing beneath the endothelial cells in both normal swine and swine with raised atherosclerotic lesions; the basement membrane that was present was often discontinuous. If the basement membrane helps regulate the transport of Evans blue dye across the arterial wall, its absence may play a part in the accumulation of the dye. In raised atherosclerotic lesions, those portions that accumulated Evans blue dye had a larger amount of amorphous extracellular matrix than did nonblue areas. No consistent difference between blue and nonblue areas were seen in the endothelial cell junctions of abdominal aortas in either control or atherosclerotic swine. Similarly, no differences were demonstrable in the number of Golgi complexes, mitochondria, or profiles of smooth or rough endoplasmic reticulum per cell.

Animals↗

[Effect of tiemonium iodide on colonic motility in dogs].

Effects of tiemonium iodide (tiemonium, 20 micrograms/kg), mepenzolate bromide (mepenzolate, 20 micrograms/kg), butylscopolamine bromide (butylscopolamine, 50 micrograms/kg) and atropine sulfate (atropine, 10 micrograms/kg) on the colonic motility in dogs were evaluated using a balloon method. The frequency of the wave motion was analyzed by fast Fourier transform, and the power spectra were obtained. The value of the first term of the power spectrum is regarded as an indication of the colonic tonus. Inhibitory effects of tiemonium on both the normal proximal colonic motility and the accelerating motility induced by neostigmine metylsulfate (neostigmine, 50 micrograms/kg) were equal to those of butylscopolamine. In the case of distal colonic motility, tiemonium showed potent mepenzolate-like inhibition. When the drugs were injected into the veins after administration of PGF2 alpha (10 micrograms/kg), all of the drugs depressed the colonic constriction induced by PGF2 alpha. The colonic motility was not restored by the administration of tiemonium or mepenzolate before the injection of PGF2 alpha, but such an effect was not observed in the case of butylscopolamine and atropine. It is suggested that tiemonium shows an extensive inhibition on the colonic motility in the mode of mepenzolate-like action and by some additional mechanism.

Animals↗

[Clinical evaluation of the serum level of immunosuppressive acidic protein (IAP) and immunosuppressive substance (IS) in gastric cancer patients].

Recently, immunosuppressive acidic protein (IAP) and immunosuppressive substance (IS) were reported by two institutions, and they have been currently under extensive clinical investigations. As these two acidic proteins seemed to be very similar glycoproteins, we tried to elucidate clinically the dissimilarities between these two substances. The mean value of IAP of 106 healthy donors was 378 +/- 100 micrograms/ml, and as 95% of them was under 550 micrograms/ml, therefore, the upper limit of normal value of IAP was determined to be 550 micrograms/ml. On the other hand, the mean value of IS was 553 +/- 125 micrograms/ml and the upper limit of normal value was 750 micrograms/ml. In 110 gastric cancer patients, the incidence of the abnormal value of IS (43%) was higher than that of IAP (33%), and abnormal values were observed at earlier stage in IS than that observed in IAP. The reaction of skin tests was more highly correlated with the value of IS than the value of IAP. From these facts, it was suggested that the value of IS was more predictable than that of IAP as the parameter of the immunosuppression of the gastric cancer patients.

Adolescent↗

[Effect of PSK on DMH (dimethyl hydrazine) induction of cancer].

The effect of PSK on the induction of intestinal tumors by DMH in Wistar rats was examined. One hundred and fifty-one rats were divided into two groups. Seventy-two rats were treated with DMH alone and 79 rats were treated with DMH and PSK. All animals were subjected to a sequential autopsy and all lesions within the GI tract were examined macroscopically and histologically. Tumor incidence in the DMH and PSK treated group was significantly lower than that in the DMH treated alone, and peritoneal disseminations and distant metastases were also significantly decreased in the PSK treated rats. The number of circulating lymphocytes dropped in the 25th and 35th week in the group treated with DMH alone, but the drop in the PSK treated group was not remarkable. DTH reaction to PPD and antibody forming capacity to SRBC were well maintained in the PSK treated rats than in those treated with DMH alone. The most interesting findings in these experiments were the differences concerning the serum blocking activities and serum immunosuppressive factor in these two groups; these were markedly reduced in PSK-treated rats. From these experiments, the mechanisms may be explained by the competitive action of PSK against the immunosuppressive factor produced by a tumor-bearing host.

Adjuvants, Immunologic↗

Comparative anatomy of the distribution of catecholamines within the inferior olivary complex from teleosts to primates.

The distribution of catecholamine (CA) in the inferior olivary complex (IO) of various vertebrate (from fish to monkey) was investigated by means of the histofluorescence technique. In addition, using rats, a further attempt was made to elucidate the origins of CA in the IO. The IO of the lower vertebrates (from fish to birds) was in general poorly innervated by the CA neuron system. IO in the lower mammals, such as insectivora and bats, contained only a few CA nerve terminals, while that in the higher mammals such as rat, guinea pig, rabbit, cat, and monkey revealed quite a number. In these animals, species-species patterns of CA nerve terminals were found. In the rat, the highest concentration was observed in the dorsal lamella of the principal nucleus and in guinea pig ventral lamella. In the rabbit and cat, maximum CA nerve terminals were detected in the dorsal accessory nucleus, while in the monkey, they were detected in the medial accessory nucleus. The retrograde tracer technique of horseradish peroxidase (HRP) suggested that the main source of the abundant CA terminals in IO of the rat might be A1, A2, and A3 noradrenaline neurons, though not locus coeruleus and not dopaminergic ones.

Animals↗

The effect of pyrazines on the metabolism of tryptophan and nicotinamide adenine dinucleotide in the rat. Evidence of the formation of a potent inhibitor of aminocarboxy-muconate-semialdehyde decarboxylase from pyrazinamide.

The intraperitoneal or oral administration of pyrazinamide and pyrazinoic acid (pyrazine 2-carboxylic acid) resulted in a marked increase of the NAD content in rat liver. The injections of pyrazine and pyrazine 2,3-dicarboxylic acid exhibited no significant effect on the hepatic NAD content. The boiled extract obtained from liver and kidney of rat injected with either pyrazinamide or pyrazinoic acid exhibited a potent inhibitory effect on the aminocarboxymuconate-semialdehyde decarboxylase (EC 4.1.1.45) activity in either lier or kidney, although pyrazinamide or pyrazinoic acid per se did not inhibit the enzyme activity. The unknown inhibitor of aminocarboxymuconate-semialdehyde decarboxylase was dialysable and heat-stable, and mostly excreted in urine by 6 and 12 h after injected of pyrazinoic acid and pyrazinamide, respectively. Pyrazine 2,3-dicarboxylic acid, pyrazine, nicotinamide, nicotinic acid, tryptophan, anthranilic acid, 5-hydroxyanthranilic acid and quinolinic acid exhibited no significant effect on the aminocarboxymuconate-semialdehyde decarboxylase activity in liver and kidney at the concentration of 1 mM in the reaction mixture. The expired 14CO2 from L-[benzen ring-U-14C]tryptophan was markedly decreased by the pyrazinamide injection, while the urinary excretion of 14C-labeled metabolites from L-tryptophan, mainly quinolinic acid, was markedly increased. These results suggest that the glutarate pathway of L-tryptophan was strongly inhibited by the inhibitor produced after the administration of pyrazinoic acid and pyrazinamide. Pyrazinamide but not pyrazinoic acid also exhibited a significant inhibition of the nuclear enzyme poly(ADP-ribose) synthetase in rat liver.

Animals↗

[Interaction of phenothiazinic anti-inflammatory agent, protizinic acid, with the biopolymers: Inhibitory effects on functions of platelets (author's transl)].

Two types of phenothiazinic anti-inflammatory agents, protizinic acid (PZA) and metiazinic acid (MZA) were examined using 1) heat denaturation test, 2) heat-induced erythrocyte lysis, 3) several platelet functions, 4) model membrane systems containing the same phospholipids and cholesterol compositions as in platelets. PZA and MZA were inhibited with heat denaturation in a similar manner seen with BSA and heat-induced erythrocyte lysis, and effects were more potent than indomethacin (IM). PZA showed inhibitory effects similar to MZA on ADP or collagen-induced platelet aggregation. However, in arachidonic acid (AA)-induced rabbit platelet aggregation, PZA had a more potent effect, similar to effects seen with IM and more potent than those of MZA. PZA inhibited the lethal effect of AA in rabbits at concentrations lower then MZA. To determine the sites of action, we examined the effects on uptake and release reactions of 3H-serotonin. PZA and MZA did not affect the uptake reaction but did reduce the release of serotonin to a greater extent than seen with IM. The tested drugs had little effect on the platelet aggregation in vivo. To investigate the interaction of these drugs with lipid bilayers, we used liposomes as a model membrane, of which the lipids compositions were the same as that of platelets. The tested drugs showed inhibitions of the liposome aggregation with addition of 6 mM Ca2+, in a dose dependent manner and similar to findings in the drug-platelet system. In this experiment, PZA had a more potent interaction with lipid bilayers than did MZA. These results suggest that interactions of PZA with the platelet membrane may be the origin of the PZA-induced inhibition of the platelet aggregation, in addition to the effect on the biosynthesis of prostaglandins.

Animals↗