Biomedical subjects

M Iigo

Publications and source records attributed to M Iigo.

At least 55 records · Page 3Linked to original sources

PubMed1995

Characterization of extrathymic T cells induced by recombinant murine interferon-beta in the peritoneal cavity of nude mice.

The effects of recombinant murine interferon-beta (rMuIFN-beta) on extrathymic lymphocyte formation in the peritoneal cavity of BALB/c athymic nude mice and tumor-bearing nude mice were examined for comparison with BALB/c normal euthymic mice. The 7 days of administration of 1 x 10(5) IU rMuIFN-beta caused the number of these cells to increase remarkably in the peritoneal cavity as a unique subset of asialoGM1+CD4+CD8-TcR alpha beta+ T cells. The asialoGM1+CD4+ T cells produced IL-2 and IFN-gamma in primary culture without stimulant but did not proliferate. Thus, extrathymic T cells can be induced easily in the peritoneal cavity in addition to the thymus for host defense systems.

Adenocarcinoma↗

PubMed1995

Characteristics of the inhibitory effect of mitoxantrone and pirarubicin on lung metastases of colon carcinoma 26.

This study was performed to evaluate the antimetastatic activity of antitumor agents against metastatic colon carcinoma 26 (Co 26Lu), and to investigate their mechanisms of action. Pirarubicin demonstrated the most striking antitumor activity in mice bearing intravenously injected Co 26Lu cells. Etoposide and mitoxantrone also showed marked antitumor activity. Pirarubicin and mitoxantrone also exerted remarkable inhibitory effect on spontaneous lung metastases from subcutaneously implanted Co 26Lu. Pirarubicin showed marked inhibition of both primary tumor growth and lung metastases. Mitoxantrone was effective in preventing lung metastases even at doses that did not exhibit an antitumor effect on the primary tumor. Moreover, mitoxantrone administered two days after intravenous injection of tumor cells obviously reduced the number of lung colonies, while simultaneous injection of the drug did not inhibit colony formation. Mitoxantrone effectively inhibited angiogenesis on the chorioallantoic membrane at doses that did not affect the growth rate of embryos. These results suggest that mitoxantrone, besides its direct antitumor effect on tumor cells, may inhibit lung metastases by inhibiting angiogenesis.

Animals↗

PubMed1995

Effects of season, temperature, and photoperiod on plasma melatonin rhythms in the goldfish, Carassius auratus.

Effects of season, environmental temperature, and photoperiod on plasma melatonin concentrations were studied in the goldfish, Carassius auratus. When goldfish were reared under natural conditions, melatonin levels at mid-dark exhibited seasonal changes, with higher levels obtained in June and September than in December and March. When fish were kept under light:dark (LD) cycle of 12:12 at 5, 15, or 25 degrees C during March-April, temperature-dependent increases in melatonin levels at mid-dark were observed. When animals were maintained under LD 16:8 or LD 8:16 in combination with temperature changes (5, 15, and 25 degrees C) during January-February, the duration of nocturnal elevation in melatonin was controlled by the length of the scotophase while the amplitude was influenced by environmental temperature. These results indicate that plasma melatonin profiles in the goldfish exhibit seasonal changes that are regulated by both photoperiod and temperature.

Animals↗

PubMed1995

Influences of season and of temperature, photoperiod, and subcutaneous melatonin infusion on the glomerular filtration rate of ewes.

Influences of season and of temperature, photoperiod, and subcutaneous melatonin infusion on glomerular filtration rate (GFR) were measured in ewes. There was a seasonal difference of GFR between summer (June-August) and winter (December-February) in Tokyo (35 degrees, 35' N); GFR was significantly (P < 0.05) higher in summer (4.2 +/- 0.3 ml/min/kg) than in winter (3.0 +/- 0.2 ml/min/kg). GFR was measured after exposure to three types of photoperiod, 24L:0D, 12L:12D, and 0L:24D, for 7 to 8 days. The value for GFR obtained at 20 degrees C was significantly lower (P < 0.05) with 0L:24D than with the other two photoperiodic conditions. GFR obtained during subcutaneous melatonin infusion (20 micrograms/hr for 16 hr/day for 7 days) with 24L:0D conditions was significantly (P < 0.05) lower (2.5 +/- 0.1 ml/min/kg) than without infusion (3.8 +/- 0.3 ml/min/kg) and was about the same as that obtained in animals under 0L:24D conditions. At 30 degrees C, GFR exhibited no difference between the 3 photoperiodic conditions and was always lower than that found at 20 degrees C. Possible influences of melatonin on GFR are discussed.

Animals↗

PubMed1995

Identification of melatonin in plants and its effects on plasma melatonin levels and binding to melatonin receptors in vertebrates.

Twenty-four edible plants were investigated for the presence of melatonin, heretofore considered to be a molecule found only in the animal kingdom. The amount of melatonin in different plants varied greatly with highest melatonin being present in plants of the rice family. Melatonin was identified by radioimmunoassay and verified by high performance liquid chromatography with fluorescence detection. Feeding a diet containing plant products rich in melatonin to chicks increased radioimmunoassayable levels of melatonin in their blood. Likewise, melatonin extracted from plants inhibited binding of [125I]iodomelatonin to rabbit brain. Thus, melatonin ingested in foodstuffs enters the blood and is capable of binding to melatonin binding sites in the brain of mammals.

Animals↗

PubMed1994

Characteristics, day-night changes, subcellular distribution and localization of melatonin binding sites in the goldfish brain.

Melatonin binding sites in the goldfish brain were characterized by radioreceptor assay using 2-[125I]iodomelatonin as the radioligand. Specific binding of 2-[125I]iodomelatonin was rapid, stable, saturable and reversible. Saturation experiments demonstrated that 2-[125I]iodomelatonin binds to a single class of receptor site with an affinity constant (Kd) of 29.8 +/- 0.7 pM and a total binding capacity (Bmax) of 11.47 +/- 0.33 fmol/mg protein at mid-light. At mid-dark, the Bmax value decreased significantly to 7.90 +/- 0.23 fmol/mg protein (P < 0.01) with no significant variation in the Kd value (33.8 +/- 1.5 pM). Competition experiments revealed the following order of pharmacological affinities: 2-iodomelatonin > melatonin > 6-hydroxymelatonin > N-acetyl-5-hydroxytryptamine > 5-methoxytryptamine > 5-methoxytryptophol > 5-methoxyindole-3-acetic acid. 5-Hydroxytryptamine, 5-hydroxytryptophol, 5-hydroxyindole-3-acetic acid, norepinephrine and acetylcholine exhibited no inhibition. Subcellular distribution of melatonin binding sites was demonstrated to be greatest in the P2 and P3 fractions as compared with the P1 fraction. Localization of melatonin binding sites in discrete brain areas was determined to be highest in the optic tectum-thalamus and hypothalamus, intermediate in the telencephalon, cerebellum and medulla oblongata, and lowest in the olfactory bulbs and pituitary gland. These results suggest that characteristics of melatonin receptors are highly conserved during evolution and that in this species melatonin plays neuromodulatory roles in the central nervous system through specific receptors.

Animals↗

PubMed1994

Enhanced therapeutic effects of anti-tumour agents against growth and metastasis of colon carcinoma 26 when given in combination with interferon and interleukin-2.

Chemoimmunotherapy of pulmonary metastases was investigated in a protocol of combined anti-tumour agents and interferon-beta and/or interleukin-2. The combination of interferon-beta and interleukin-2 after treatment with etoposide or cisplatin exerted profound therapeutic effects in an experimental model (lung colonization) using colon carcinoma 26, which was resistant to interferon-beta or to interleukin-2 alone. Cured mice treated with anti-tumour agents and cytokines rejected re-implanted tumours. Moreover, this approach also had profound effects on spontaneous pulmonary metastases, together with the effect on primary tumours. However, this combination of cytokines did not enhance the anti-tumour activity of etoposide in athymic mice with pulmonary metastases. Injections of tumour-bearing BALB/c mice with a combination of etoposide and these cytokines resulted in a marked increase in CD8+, asialo-GM1+ cells. Thus the combined treatment with interferon-beta and interleukin-2 after administration of cytotoxic drugs may induce specific anti-tumour immunity, and such combinations may offer a new approach to the development of effective therapy for cancer metastases.

Animals↗

PubMed1994

Melatonin signal transduction in the goldfish, Carassius auratus.

Generation and reception of melatonin signals in the goldfish, Carassius auratus, are reviewed. The photoreceptive pineal gland of the goldfish generates circulating melatonin rhythms according to a given photoperiod under light-dark cycles and in a circadian manner under continuous dark conditions. Melatonin is also produced in the retina in a similar fashion. Melatonin produced in the pineal gland and retina is considered to act as internal zeitgeber in the brain and retina, respectively, controlling various physiological events via specific melatonin binding sites that are coupled with G protein. The goldfish exhibit clear diurnal locomotor activity rhythms under light-dark cycles and free-running rhythms under constant conditions. However, the relationship between melatonin and locomotor activity rhythms in the goldfish remains unclear. Further studies should be required to demonstrate the roles of melatonin in the circadian system in this species.

Animals↗

PubMed1994

Chemopreventive effects of beta-carotene, alpha-tocopherol and five naturally occurring antioxidants on initiation of hepatocarcinogenesis by 2-amino-3-methylimidazo[4,5-f]quinoline in the rat.

Inhibitory effects of naturally occurring antioxidants on the initiation stage of hepatocarcinogenesis were studied. Group 1 rats were given a diet containing beta-carotene (beta-CT, 0.02%), alpha-tocopherol (alpha-TP, 1.5%), glutathione (GLT, 5%), vanillin (VNL, 1%), quercetin (QCT, 1%) or ellagic acid (ELA, 1%), or 3 doses of diallyl sulfide (DAS, 200 mg/kg, i.g.) over an 8-day period. On day 7, the animals received a single dose of 2-amino-3-methylimidazo[4,5-f] quinoline (IQ, 100 mg/kg, i.g.), 12 h after two-thirds partial hepatectomy for initiation and 2 weeks thereafter, were placed on promotion regimen comprising phenobarbital (0.05% in diet) and a single dose of D-galactosamine (100 mg/kg, i.p.). Groups 2 and 3 were treated as described for Group 1, but without test material or IQ, respectively. Survivors were killed at week 11 and antioxidant influence was assessed by comparing values for preneoplastic glutathione S-transferase placental form-positive (GST-P+) foci between Groups 1 and 2. All lesions larger than 70 microns in diameter consisting of approximately 5 cells in cross section were counted. Numbers of GST-P+ foci/cm2 in Group 1 were: beta-CT, 7.99; alpha-TP, 8.21; GLT, 9.71; DAS, 10.37; VNL, 10.57; QCT, 11.1; ELA, 12.5 (n = 11-15). All, except ELA, showed a significant decrease as compared with the Group 2 value of 14.54 (n = 15). Only beta-CT showed a significant decrease for the area value. This is the first report to show that beta-CT, alpha-TP, GLT, DAS, VNL, QCT exert inhibitory effects on initiation of hepatocarcinogenesis by the food carcinogen IQ, suggesting that these antioxidants might find application as chemopreventive agents. Furthermore, the current protocol proved practical for the assessment of chemopreventive agents within 11 weeks, a relatively short period.

Allyl Compounds↗

PubMed1993

Relationship between development of diarrhea and the concentration of SN-38, an active metabolite of CPT-11, in the intestine and the blood plasma of athymic mice following intraperitoneal administration of CPT-11.

Severe diarrhea occurred during daily intraperitoneal administration of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) at a dose of 50 mg/kg in athymic mouse. Serial determination of CPT-11 and 7-ethyl-10-hydroxycamptothecin (SN-38), with the use of an on-line solid extraction HPLC system, demonstrated that much higher levels of the compounds are retained in the intestine and the blood plasma after five consecutive daily injections than after a single injection. Histologic examination of the gastrointestinal tract showed hemorrhagic colitis on day 7 and later after five consecutive daily injections of CPT-11. The direct cause of diarrhea associated with CPT-11 administration is considered to be enterocolitis caused by high levels of SN-38 and/or CPT-11 retained for a long period in the intestine.

Animals↗

PubMed1993

Synergistic antitumor effects of carboplatin and interferons on hepatic metastases of colon carcinoma 26 and M5076 reticulum cell sarcoma.

The effects of combination therapy including various antitumor agents and interferon on mice bearing hepatic metastases of colon carcinoma 26 were determined. Combined treatment with interferon-alpha A/D and carboplatin (CBDCA) was associated with a considerably more pronounced antitumor effect than was treatment with either drug alone. Murine interferon-beta and -gamma each also potentiated the antitumor activity of CBDCA. Combination therapy with interferon-alpha A/D and CBDCA also resulted in marked inhibition of hepatic metastasis of M5076 reticulum cell sarcoma. However, interferon-beta did not potentiate the antitumor activity of CBDCA against either subcutaneously implanted colon carcinoma 26 or pulmonary metastases of this tumor. Thus, in our model the combined administration of interferon and CBDCA was associated with a synergistic antitumor effect on hepatic metastases alone.

Animals↗

PubMed1992

Antitumor effect and tumor level of 5-fluoro-2'-deoxyuridylate following oral administration of tetradecyl 2'-deoxy-5-fluoro-5'-uridylate.

The antitumor effect and tumor levels of 5-fluoro-2'-deoxyuridylate (FdUMP) following oral administration of tetradecyl 2'-deoxy-5-fluoro-5'-uridylate (TT-62) were compared with those attained following intravenous (i.v.) or intraperitoneal (i.p.) administration of 5-fluorouracil (5-FU) or 5-fluoro-2'-deoxyuridine (FUdR) in BDF1 mice bearing murine mammary adenocarcinoma 755 and athymic mice bearing the transplantable human colon adenocarcinoma LS174T. Oral administration of TT-62 showed a stronger antitumor effect against adenocarcinoma 755 than FUdR. The maximum effect of TT-62 was similar to that of 5-FU. However, TT-62 and FUdR treatments were more effective than i.v. administration of 5-FU against LS174T. Thus, oral administration of TT-62 showed marked antitumor activity in both tumor systems. The maximum tolerated dose of FUdR resulted in a much higher level of free FdUMP in the LS174T tumor than that obtained with 5-FU. After oral administration of TT-62 the levels of FdUMP in the tumor were about 10 times those attained with 5-FU, but significantly lower than the levels obtained following i.v. administration of FUdR. With TT-62 the levels of FdUMP in the tumor reached their peak at 60 min following the administration and gradually decreased thereafter. However, FdUMP levels after administration of FUdR decreased rapidly. Three hours after the administration of TT-62 and for up to 24 h the FdUMP levels in the LS174T tumor were almost the same as after administration of FUdR, i.e. effective levels of FdUMP were maintained for a long time with TT-62.

Adenocarcinoma↗

PubMed1992

In vivo antitumor effects of fluoropyrimidines on colon adenocarcinoma 38 and enhancement by leucovorin.

Antitumor effect and active metabolites of fluoropyrimidines were examined in mice with transplantable colon adenocarcinoma 38 (Co 38). 5-Fluoro-2'-deoxyuridine (FUdR) treatment resulted in a much higher level of free 5-fluoro-2'-deoxyuridine-5'-monophosphate in the tumor than 5-fluorouracil (5-FU) did, and thymidylate synthase was almost completely inhibited after FUdR treatment, but FUdR showed weaker antitumor activity than 5-FU did. Moreover, 5-fluorouridine (FUR) also hardly inhibited tumor growth. A more marked tumor inhibition was obtained when FUdR and FUR were administered together. The antitumor activity of 5-FU was similar to that of the combination of FUdR and FUR. In combination with 2,2'-anhydro-5-ethyluridine, a uridine phosphorylase inhibitor, FUdR lost its antitumor activity, but that of FUR was somewhat potentiated. On the other hand, in combination with leucovorin (LV), 5-FU showed markedly potentiated antitumor activity, while the antitumor activity of FUdR or FUR was not potentiated. Addition of LV to the combination of FUdR and FUR enhanced the inhibitory effect of the drugs. From these results, the combination of FUdR and FUR together with LV, and the combination of 5-FU and LV seem to be highly efficacious against Co 38.

Adenocarcinoma↗

PubMed1992

Effects of antitumor agents on subcutaneous implants and hepatic metastases of colon carcinoma 26 in mice.

We investigated the responses of experimentally produced hepatic metastases of colon carcinoma 26 tumor and subcutaneously (SC) implanted colon carcinoma 26 tumor in mice to 17 clinically-used and one under-development antitumor agents using same dose regimen. In intravenous administrations on days 7 and 14, there were no significant differences in their responses to most of the tested agents. However, there were big differences in the responses to some of the agents. Nimustine more effectively prolonged the lifespan of SC implanted tumor-bearing mice than of mice bearing hepatic metastases. Mitomycin C was, however, considerably more effective on hepatic metastases than on SC implanted tumor. ME2303, a new fluorinated anthracycline derivative, showed a similar effect to doxorubicin on both tumors. However, administrations of ME2303 on days 7, 11 and 15 showed more marked antitumor effect only on hepatic metastases than administrations on days 7 and 14. Doxorubicin was less active against both tumors for administrations on days 7, 11 and 15 than for those on days 7 and 14. These results suggest the importance of the site of tumor growth for the action of some drugs. ME2303 may be active against hepatic metastases if it is administered by multiple injections.

Alanine Transaminase↗

PubMed1992

Increase in ubiquitin-immunoreactive nuclei in rat pituitary luteinizing hormone cells after castration.

Immunocytochemical detection of ubiquitin in the nucleus of rat LH cells and the effects of castration and testosterone replacement on the occurrence of immunoreactive ubiquitin in the nucleus were investigated. Immunoreactive ubiquitin occurred in certain nuclei, mostly belonging to identified LH cells. The concentration of testosterone in blood was altered by castration and implantation of testosterone into castrated rats, and the occurrence of ubiquitin was examined weekly for the following 4 weeks. In castrated rats, the proportion of LH cells with ubiquitin-immunoreactive nuclei was high throughout the experiment. In castrated rats implanted with testosterone, on the contrary, the proportion remained significantly lower. Ubiquitin may be involved in the cellular activity of LH cells in the rat pituitary.

Animals↗

PubMed1991

Circadian rhythms of melatonin secretion from superfused goldfish (Carassius auratus) pineal glands in vitro.

A flow-through, whole-organ culture (superfusion) system was developed, and goldfish pineal glands were maintained at 25 degrees under light-dark (LD) 12:12 cycles, reversed LD 12:12 cycles, continuous dark (DD), or continuous light (LL) conditions for 48 hr. Under LD 12:12 and reversed LD 12:12 cycles, superfused pineal glands showed a rhythmic melatonin secretion: Scotophase was associated with high titers and photophase with low titers. The melatonin secretion rhythms persisted for two cycles under DD conditions, whereas nocturnal rises were suppressed under LL conditions. After the transition from LL to DD conditions on the third day, melatonin showed a nocturnal increase. These results indicate that melatonin secretion from the superfused goldfish pineal gland is directly photosensitive and that the goldfish pineal gland harbors a circadian oscillator which generates melatonin secretion rhythms.

Animals↗

PubMed1991

Effects of anthracycline derivatives on hepatic neoplastic nodules of Lewis lung carcinoma and colon adenocarcinoma 26.

Five anthracycline derivatives, i.e. doxorubicin, epirubicin, pirarubicin, aclarubicin and a new fluorinated anthracycline derivative (ME2303), were tested for antitumour activity in mice with hepatic neoplastic nodules of Lewis lung carcinoma and colon adenocarcinoma 26. Intravenous administrations of pirarubicin and ME2303 on day 4 or days 4, 8 and 12 in mice with hepatic neoplastic nodules of Lewis lung carcinoma rendered more than 50% of mice tumour-free over wide ranges of nontoxic doses, whereas a few mice were cured by treatment with doxorubicin and no mice were cured by treatment with epirubicin or aclarubicin. Moreover, when ME2303 was administered at 50 mg kg-1 on days 7, 11 and 15 to six mice bearing more advanced hepatic tumours, five were cured, while pirarubicin and doxorubicin never achieved cure. Furthermore, in mice with hepatic neoplastic nodules of colon adenocarcinoma 26, ME2303 also showed a marked antitumour effect compared to pirarubicin or doxorubicin. Two or three injections of ME2303 starting from day 7 conferred a greater antitumour effect than did more fractionated or single-dose regimens.

Adenocarcinoma↗

PubMed1991

Antitumor activity and metabolism of a new anthracycline-containing fluorine (ME2303) in Lewis lung carcinoma-bearing mice.

(7-O-(2,6-Dideoxy-2-fluoro-alpha-L-talopyranosyl)adriamycinone-14- hemipimerate (ME2303) showed a more marked growth inhibition of Lewis lung carcinoma than adriamycin (ADM). When administered to s.c. Lewis lung carcinoma-bearing mice, ME2303 in the plasma and liver was rapidly metabolized and disappeared. However, ME2303 was incorporated into the tumor at higher concentrations and remained in the tumor for a longer period than in the plasma and liver. ME2303 was metabolized to 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl)adriamycinone (M1), the product of esterolysis, and its reduced derivative at the C-13 position (M2). Larger amounts of these metabolites were found in the analyzed tissues than in plasma. The maximum concentration of M1 in the tumor was observed at 2 h posttreatment, while the maxima in the plasma and liver were observed at 15 min. On the other hand, i.v. injection of M1 into mice showed a weaker antitumor effect than ME2303 injection, though M1 levels in the plasma and tumor were almost the same as those after administration of ME2303 at the maximum tolerated doses. Some metabolites of ME2303 were found in the tumor after administration of ME2303, but not after administration of M1. ADM remained in the analyzed tissues for a long period and ADM concentrations in the tumor were much higher than in the plasma but less than in the liver. M1 reached a concentration higher than that of ADM in the tumor, opposite to the pattern observed in the liver. The conversion process from ME2303 to M1, the metabolites and their locations in the tumor may be important for the marked antitumor effect of ME2303 in vivo.

Animals↗