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Biomedical subjects

R Imai

Publications and source records attributed to R Imai.

At least 55 records · Page 3Linked to original sources
PubMed1990

Prostacyclin and beraprost sodium as suppressors of activated rat polymorphonuclear leukocytes.

Beraprost sodium (beraprost) is a stable analogue of prostaglandin I2 (PGI2), which can be administrated orally. In the present study, the effect of beraprost on the activation process of polymorphonuclear leukocytes (PMNs) was examined in vitro. Beraprost effectively inhibited chemotaxis of PMNs induced by formyl-methionyl-leucyl-phenylalanine (FMLP). Like prostaglandin E2 (PGE2), beraprost elevated intracellular cAMP level and inhibited the influx of extracellular Ca2+ in PMNs. The concentration-response curves showed that the inhibitory effect of beraprost on chemotaxis was correlated with the increment of intracellular cAMP level of the PMNs and inhibition of influx of extracellular Ca2+. Beraprost also inhibited inositol phospholipid metabolic turnover and superoxide anion production of PMNs induced by FMLP at relatively high concentration. These results suggest that the inhibitory effect of beraprost on the PMN function especially chemotaxis is mediated through the elevation of the intracellular cAMP level, which interferes with the signal transduction process probably through the inhibition of Ca2+ mobilization in PMNs. The above-mentioned effects of beraprost were also the case with PGI2. The potency of beraprost was comparable to PGI2 in the present study. Considering its stability, these results thus raise a possibility that beraprost might exert anti-inflammatory effect in vivo.

Animals↗
PubMed1990

A procedure for recording electroretinogram and visual evoked potential in freely moving cats.

A procedure for recording the electroretinogram (ERG) and the visual evoked potential (VEP) in freely moving cats was developed and used to test the visual toxicity of nalidixic acid. The electrodes for recording the ERG and VEP were implanted chronically in the sclera of the eye and on the surface of the visual cortex, respectively. Both the ERG and VEP were simultaneously recorded in freely moving cats using a slip ring that allows the cat to move freely without twisting the cables. After a 15-min dark-adaptation period, 20 responses to repetitive photic stimulation with an intensity of 2 joules and a 10-sec interstimulus interval were averaged by means of a minicomputer. The waveform of the ERG consisted of a negative wave (a-wave) followed by a positive wave (b-wave) with 2 to 3 oscillatory potentials on the rising slope. The VEP consisted of initial positive wave (P1 wave) followed by a negative wave (N1 wave) and late positive and negative deflections. The amplitude of the components of the ERG and VEP varied considerably from animal to animal, whereas within the same animal they were very stable. Using this technique, the effects of nalidixic acid, a retinotoxic compound, on the ERG and VEP were studied. Nalidixic acid produced a marked, but transient, decrease in the amplitude of the ERG b-wave after a single intravenous injection at a dose of 10 mg/kg. After repeated doses at 40 mg/kg/day for 2 weeks, the reduction in the amplitude of the b-wave was stronger, but remained transient. Upon ophthalmologic and histopathologic examination of the retina, no abnormalities indicating visual toxicity were observed. These results indicate that this procedure for recording the ERG and VEP is useful for evaluating the visual toxicity of drugs in freely moving cats.

Animals↗
PubMed1990

[Significance of HLA-DR+ T cells and natural killer (NK) cells in the peripheral blood lymphocytes of alopecia areata (AA)].

HLA-DR+ T cell and NK cell subsets in peripheral blood lymphocytes of patients with AA were investigated. The percentages of HLA-DR+ T cell and NK cell subsets from a mild condition of patchy AA and an acute condition of alopecia totalis, for which hair regrowth occurred frequently with ease, were similar to those of the normal control. On the other hand, the percentages of HLA-DR+ Leu3a+ cells HLA-DR+ Leu2a+ cells and Leu7-Leu11+ cells from a severe condition of patchy AA and alopecia universalis, for which hair regrowth did not easily occur, were significantly higher than those of the normal control. The increase in the percentages of HLA-DR+ Leu3a+ cells, HLA-DR+ Leu2a+ cells and Leu7-Leu11+ cells from the severe condition of patchy AA and alopecia universalis was lessened and normalized by treatment with betamethasone. These findings suggest that the auto-immune disorders of HLA-DR+ T cell and NK cell may play important roles in disease activities related to severe patchy AA and alopecia universalis.

Administration, Topical↗
PubMed1989

Intravenous administration of isosorbide dinitrate attenuates the pressor response to laryngoscopy and tracheal intubation.

In order to evaluate the effect of isosorbide dinitrate (ISDN), administered as a bolus intravenous injection, on the circulatory response to tracheal intubation, mean arterial pressure (MAP), and heart rate (HR) in response to laryngoscopy for 30 s followed by tracheal intubation were compared in patients not receiving ISDN (control) and receiving 40 micrograms/kg or 80 micrograms/kg of ISDN 45 s before starting laryngoscopy. Each group consisted of 10 patients undergoing elective surgery. Forty-five seconds after starting laryngoscopy, MAP was significantly (P less than 0.01) lower in patients receiving 80 micrograms/kg ISDN than in those receiving no or 40 micrograms/kg ISDN. HR increased to a similar extent in the three groups. These results indicate that a bolus injection of ISDN (80 micrograms/kg) is a simple, practical and highly effective means of attenuating the hypertensive response to direct laryngoscopy and tracheal intubation.

Adult↗
PubMed1989

[Increase in Leu7- Leu11+ cells in the peripheral blood lymphocytes of patients with alopecia areata].

Natural killer (NK) cell subsets in the peripheral blood lymphocytes of patients with alopecia areata (AA) were investigated by FACStar-I using NK cell specific monoclonal antibodies. The patients were classified into one of 2 types (Type A: single AA in regrowth phase; Type B: multiple AA, alopecia totalis and alopecia universalis in non-regrowth phase). The percentages of Leu7- Leu11+ cells in Type B were significantly higher than those of the normal control. The increase in Leu7- Leu11+ cells in Type B suggests that NK cells may play an important role in the pathogenesis of AA in the non-regrowth phase.

Adult↗
PubMed1989

[Correlation of activated T cells and natural killer (NK) cells with the disease activity of alopecia areata (AA)].

Patients with AA were classified into one of two types (Type A: active AA with less than 3 patches; Type B: active AA with 10 or more patches). The percentages of activated T cell subsets and NK cell subsets in the peripheral blood of Type A were similar to those of the normal control. On the other hand, the percentages of HLA-DR+ Leu2a+ cells, HLA-DR+ Leu3a+ cells, Leu7+ Leu11+ cells and Leu7- Leu11+ cells in Type B were significantly higher than those of the normal control. These findings suggest that activated T cells and NK cells play an important role in the disease activity of AA.

Adult↗
PubMed1985

Origin and properties of the blister formation factor in blister fluids from recessive dystrophic epidermolysis bullosa.

The origin and properties of the blister formation factor in recessive dystrophic epidermolysis bullosa (RDEB) blister fluids were investigated. Organ cultures of normal human skin incubated with RDEB dermis extract or with RDEB fibroblast culture medium (FCM) produced a clear subepidermal blister with histology similar to that of a RDEB blister in vivo. The injection of RDEB dermis extract into guinea-pig skin also induced dermal-epidermal separation with similar histology to the skin lesions of RDEB patients. The blister forming activity of RDEB FCM which induces the subepidermal blister was inactivated by heat (60 degrees C for 30 min), trypsin digestion and by treating with EDTA, EGTA, alpha 2-macroglobulin, diisopropyl fluorophosphate and N-ethylmaleimide, but was not affected by dialysis. These results suggest that the RDEB fibroblast produces a blister formation factor(s), and that blister formation may be caused by a combination of a metallo-protease, serine protease and SH protease.

Animals↗
PubMed1985

Antitumor activity of echinosporin.

Echinosporin isolated from a Streptomyces culture showed antitumor activity against rodent tumor models such as leukemia P388, P388/VCR, and fibrosarcoma Meth 1. It was marginally active against melanoma B16 and sarcoma 180. It was not active against Lewis lung carcinoma and xenograft MX-1. It inhibited the colony formation of HeLa S3 cells with a wide shoulder at low dose ranges. DNA, RNA, and protein synthesis were inhibited by echinosporin. It depressed WBC with nadir on day 3, but the recovery to the normal level after echinosporin injection was more rapid than that after mitomycin C.

Animals↗
PubMed1983

Comparative antitumor activities of 7-N-(p-hydroxyphenyl)mitomycin C (M-83) and mitomycin C.

The antitumor activity of 7-N-(p-hydroxyphenyl)mitomycin C (M-83) against 7 kinds of ascitic tumors and 4 kinds of solid tumors was compared with that of mitomycin C (MMC). M-83 showed more potent activities than MMC against ascites sarcoma 180, fibrosarcoma Meth 1, sarcoma Meth A, melanoma B-16, leukemia P388 and lymphoma EL4, by a single intraperitoneal injection. Furthermore, M-83 gave markedly higher chemotherapeutic ratio than MMC in these tumor systems. M-83 was also markedly effective against solid tumors of sarcoma 180, Meth 1, Meth A and Lewis lung carcinoma, by a single intravenous injection. M-83 gave lower myelo-suppression than MMC at the doses which gave almost equal inhibition on the tumor growth of solid Meth 1. M-83 and MMC significantly inhibited the growth of HeLa S3 cells. Cell growth was observed at 24 hours after addition of 3 X 10(-3) mM of drugs, but no growth was shown thereafter. M-83 inhibited more strongly the incorporation of the radioactive precursor into DNA than that into RNA or protein at the concentration of 3 X 10(-3) mM.

Animals↗
PubMed1982

The action of 7-N-(p-hydroxyphenyl)mitomycin C [M-83] in suppressing murine immune response.

The immuno-suppressive activities of 7-N-(p-hydroxyphenyl)mitomycin C [M-83], a derivative of mitomycin C (MMC), which has better antitumor activity against murine tumors, was investigated in mice. A single injection of M-83 induced an apparent but relatively transient reduction in both plaque-forming cell production and delayed type hypersensitivity reaction to sheep red blood cells. The suppressive effect of M-83 was significantly milder than that of MMC at the same effective and molar equivalent doses. Moreover, the recovery from immunosuppression induced by M-83 was also relatively rapid as compared with MMC. The inhibiting activity of M-83 against the blastogenic response of spleen cells was milder in vivo, but was more significantly cytotoxic in vitro than that of MMC.

Animals↗
PubMed1982

Distribution and excretion of 7-N-(p-hydroxyphenyl)-mitomycin C in normal mice.

Tissue distribution, excretion and stability of 7-N-(p-hydroxyphenyl)-mitomycin C (M-83) in normal mice were compared with those of mitomycin C (MMC) by microbiological assay. M-83 was more rapidly inactivated by mouse liver homogenate in vitro than MMC. MMC could not be detected by thin-layer chromatography-bioautography in the reaction mixture of M-83 incubated with mouse liver homogenate, or in the mouse urine. Both M-83 and MMC exhibited biphasic serum elimination characteristics after iv bolus injection. When these compounds were administered at their approximate LD50 (M-83, 20 mg/kg; MMC, 8 mg/kg) iv into mice, their half-lives were 17.9 and 19.8 min, respectively. However, the half-life of M-83 (10.2 mg/kg) after iv bolus injection was 7.5 min and was shorter than that of MMC (8 mg/kg) at the molar equivalent dose. In ip administration of an approximate LD50, M-83 and MMC exhibited similar drug absorption and elimination patterns. When both compounds were administered iv at the approximate LD50, the 24-hr urinary recoveries of unchanged M-83 and MMC were 2.85 and 19.26%, respectively. The distribution of M-83 in various tissues was similar to that of MMC.

Animals↗
PubMed1981

Antitumor activity of 7-n-(p-hydroxyphenyl)-mitomycin C in experimental tumor systems.

The antitumor activity of 7-N-(p-hydroxyphenyl)-mitomycin C (M-83) was compared with that of mitomycin C (MMC) in rodent tumor systems. M-83 exhibited more potent activity than MMC against the ascitic form of lymphocytic leukemia P388 and fibrosarcoma Meth 1, and doses of over 5 mg/kg of M-83 (1/6 LD50) resulted in some 60-day survivors. The chemotherapeutic ratio (optimal dose/MED) of M-83 was around 64 and was estimated to be approximately 5 to 8 times higher than that of MMC. Upon intravenous administration, M-83 also gave a better survival and showed a higher chemotherapeutic ratio than MMC against intravenously implanted P388. M-83 inhibited the growth of solid form of sarcoma 180 to the same extent as MMC at an equivalent dose, but showed a higher safety margin than MMC. M-83 was as effective as MMC against Lewis lung carcinoma at dose levels giving the same degree of toxicity. In vitro studies on tumor growth inhibition demonstrated that the cytotoxic effects of M-83 against leukemia P388 and fibrosarcoma Meth 1 cells were similar to and stronger than those of MMC, respectively.

Animals↗
PubMed1981

Comparison of the hematologic toxicity of 7-N-(p-hydroxyphenyl),-mitomycin C and mitomycin C.

7-N-(p-Hydroxyphenyl)-mitomycin C (M-83), a new analog of mitomycin C (MMC) with equivalent or greater antitumor potencies against various experimental tumors, was investigated to determine its hematologic toxicity in mice. M-83 showed a significantly lower toxicity than MMC with respect to myelosuppression and leukopenia when compared at equivalent effective doses. In M-83-treated mice, the damage to the bone marrow was much milder at the nadir point and the recovery from myelosuppression to the normal level was faster as compared with that in the case of MMC. As a result, the number of white blood cells in the peripheral blood of the M-83-treated groups was considerably greater than that in the MMC-treated ones. These findings suggest that M-83 may be effective in clinical use.

Animals↗