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Biomedical subjects

Y Mimura

Publications and source records attributed to Y Mimura.

At least 91 records · Page 5Linked to original sources

Chemical structure-activity of cnidium rhizome-derived phthalides for the competence inhibition of proliferation in primary cultures of mouse aorta smooth muscle cells.

Inhibitory effects of cnidium rhizome-derived phthalides on competence and progression phases of fetal bovine serum (10%)-induced proliferation were compared in primary cultures of mouse aorta smooth muscle cells (SMC). Their potencies for the competence inhibition were in the order of senkyunolide L ((Z)-6-hydroxy-7-chloro-6,7-dihydroligustilide) > senkyunolide H ((Z)-6,7-dihydroxy-6,7-dihydroligustilide) > senkyunolide J ((3S)-(E)-6,7-dihydroxy-3,6,7,8-tetrahydroligustilide) > senkyunolide I ((E)-6,7-dihydroxy-6,7-dihydroligustilide) > ligustilide = senkyunolide A ((3S)-3,8-dihydroligustilide) > butylidenephthalide. The order of their potencies for the progression inhibition was parallel with that for the competence inhibition. Senkyunolide L is considered to have been formed during the extraction of cnidium. These results demonstrate that the (Z)-6,7-dihydroxy isomer of the dihydroligustilide derivatives is essential for the anti-competent effect on proliferation of the SMC in primary culture. Senkyunolide H in cnidium rhizome may be a prototype for a new anti-atherosclerotic drug.

4-Butyrolactone

AB5046A and B, novel chlorosis-inducing substances from Nodulisporium sp.

Novel chlorosis-inducing substances, AB5046A and B, were isolated from the culture broth of a fungal strain. The producing organism, designated AB5046, was identified as a member of Nodulisporium. AB5046A and B were purified by extraction with EtOAc and silica gel chromatography. The structure of AB5046A and B were determined to be 2-butyryl-3,5-dihydroxy-cyclohex-2-ene-1-one and 2-acetyl-3,5-dihydroxy-cyclohex-2-ene-1-one, respectively, by spectroscopic analyses. AB5046A and B induced chlorosis against Japanese barnyard millet in vitro. The chlorosis activity of these compounds was stronger against monocotyledons than dicotyledons.

Animals

Erythropoietin production in hepatocellular carcinoma cells associated with polycythemia: immunohistochemical evidence.

Patients with hepatocellular carcinoma sometimes have erythrocytosis and high plasma erythropoietin levels. However, previous studies have not revealed direct evidence that the carcinoma cells produce the erythropoietin. To address this question, we carried out light and electron microscopic immunohistochemical studies, using a human erythropoietin antibody to the liver in three male patients with hepatocellular carcinoma and erythrocytosis. alpha-Feto-protein localization was also examined in serial liver sections by light microscopic immunohistochemistry with an antibody to alpha-fetoprotein. All three patients demonstrated high hemoglobin levels (16.7, 17.6 and 18.1 gm/dl) and high plasma erythropoietin levels (227, 266 and 280 mU/ml). In one patient the plasma erythropoietin level in the hepatic vein was significantly higher than that in the hepatic artery. The levels of plasma erythropoietin, as well as such tumor markers for hepatocellular carcinoma as serum alpha-fetoprotein and plasma des-gamma-carboxyprothrombin, were significantly reduced after treatment with an anticancer drug, cisplatin. Light microscopic immunohistochemistry showed that erythropoietin was definitely present in the cytoplasm of the hepatocellular carcinoma cells, but not in normal hepatocytes around the carcinoma lesion or in other nonparenchymal cells such as vascular endothelial cells and Kupffer cells. In electron microscopic immunohistochemistry, reaction products for erythropoietin were revealed in the cisternae of the endoplasmic reticulum in the carcinoma cells, suggesting the production of erythropoietin by these cells. Light microscopic immunohistochemistry showed that alpha-fetoprotein was localized in the hepatocellular carcinoma cells that were erythropoietin positive in the serial sections. These findings indicated that hepatocellular carcinoma cells produced erythropoietin as well as alpha-fetoprotein in these cases, leading to the complication of erythrocytosis.

Aged

Analysis of the interaction between an alpha (1----6)dextran-specific mouse hybridoma antibody and dextran B512 by affinity electrophoresis.

Carbohydrates are common environmental antigens. As dextran B512 is composed of a repeating structure of simple antigenic determinants, it is widely used to study the immunochemical properties of immunoglobulins. Two-dimensional affinity electrophoresis patterns of a mouse monoclonal antidextran antibody (35.8.2H; IgG1, BALB/c) were produced to obtain insights into the microheterogeneity of the monoclonal antibody. The monoclonal antibody was separated into about six spots which had an identical affinity to dextran B512, but differed in their isoelectric points (pI). In addition, the pH dependence of the binding affinity of this antidextran to dextran B512 was examined. By comparing affinities obtained by affinity electrophoresis between weakly basic (pH 9.5) and weakly acidic (pH 3.8) discontinuous buffer systems, the latter showed an affinity about 500 times lower than the former. The change in the affinity was investigated with a continuous pH gradient by an affinity titration curve and was seen to change markedly at about pH 6. This suggests that the histidine at residue 34 in the light-chain CDR1 is largely responsible for the dextran binding.

Amino Acid Sequence

Kinetic properties of the bovine corneal aldehyde dehydrogenase (BCP 54).

The major soluble protein of bovine cornea (BCP 54: bovine corneal protein 54 kDa) was isolated successively by gel filtration, anion-exchange chromatography and chromatofocusing. The amino acid sequence of a fragment of the purified BCP 54 obtained by lysyl-endopeptidase digestion showed marked homology with tumor-associated and 2,3,7,8-tetrachloro-dibenzo-p-dioxin-inducible aldehyde dehydrogenase (AIDH). From the high similarity of BCP 54 with tumor-associated AIDH in structural form, it is suggested that BCP 54 has AIDH activity. We confirmed a high AIDH activity of BCP 54 by immunoprecipitation using a mouse anti-BCP 54 monoclonal antibody followed by a spectrophotometric assay for AIDH activity. Next we demonstrated the unique properties of the purified BCP 54 as AIDH. The major isoelectric point is 6.41. BCP 54 preferentially oxidizes aromatic aldehyde such as benzaldehyde with NAD as coenzyme, but cannot oxidize phenylacetaldehyde. After heat treatment the AIDH activity is more stable with propionaldehyde-NAD than with benzaldehyde-NADP. With propionaldehyde-NAD the pH profile shows a broad plateau from pH 6-9 followed by a sharp rise up to pH 10. In contrast, with benzaldehyde-NADP there is a sharp optimum at pH 9.0. The activity with only benzaldehyde-NADP is inhibited by p-hydroxymercuribenzoate, but is not affected by disulfiram and diethylstilbestrol. So we suggested that BCP 54 is an AIDH with kinetic properties different from the rat tumor-associated AIDH.

Aldehyde Dehydrogenase

N.m.r. study of interaction between sugar and peptide moieties in mucin-type model glycopeptides.

In order to investigate the structural properties of the sugar and peptide linkage region in glycoprotein, some glycopeptides were synthesized as a model for AFGP (antifreeze glycoprotein), which is one of the mucin-type glycoproteins. The results from n.m.r. measurements in DMSO and aqueous conditions revealed that the glycopeptides form an intramolecular hydrogen bond between the amide proton of N-acetylgalactosamine (GalNAc) and the carbonyl oxygen of threonine (Thr) to which the GalNAc is covalently linked. This intramolecular hydrogen bond may play an important role in determining the orientation of the sugar moiety relative to the protein backbone. The roles for the activity of the proline (Pro) residue in AFGP were also discussed.

Amino Acid Sequence

Antiproliferative effects of the traditional Chinese medicine shimotsu-to, its component cnidium rhizome and derived compounds on primary cultures of mouse aorta smooth muscle cells.

Antiproliferative effects of the Japanese-Sino medicine Shimotsu-to (a combined prescription of cnidium rhizome, angelica root, peony root and rehmannia root) were investigated in the primary culture of smooth muscle cells (SMC) of mouse aorta. Fetal bovine serum (10%)-induced proliferation of primary cultured SMC was inhibited by Shimotsu-to at 4, 20, 100 or 500 micrograms/ml. The inhibitory effect was selective on SMC and due to cnidium rhizome or angelica root. The IC50 values of senkyunolide H, senkyunolide A, ligustilide and butylidenephthalide derived from cnidium were below 0.1, 1.52, 1.68 and 3.25 micrograms/ml, respectively. These results indicate that the antiproliferative effect of Shimotsu-to may depend on these cnidium-derived phthalides.

Animals

AB3217-A, a novel anti-mite substance produced by a strain of Streptomyces platensis.

AB3217-A, a novel anti-mite substance, was isolated from the fermentation broth of a streptomycete strain. The strain was isolated from a soil collected at Kita-azumi, Nagano Prefecture, Japan, and identified as Streptomyces platensis AB3217. AB3217-A was purified by Amberlite IR120B, Diaion HP-20 and CM-Sephadex C-25 column chromatographies. The molecular formula was determined as C17H23NO7 by elemental analysis, MS and 13C NMR spectroscopy. The structure of AB3217-A was determined to be (1R,3S,4S,7R,8R,11R,12S,13R)-4,12,13-trihydroxy-8-(4-methoxy phenyl)-6-aza-2,9,14-trioxatricyclo-[9.2.1.0(3,7)]tetradecane by spectroscopic analysis and X-ray crystallographic analysis. The molecule of AB3217-A has unique structure that deacetylanisomycin and beta-D-xylofuranose linked through glycosidic bond and ether bond resulting in the formation of nine-membered ring. AB3217-A showed marked activity against the two spotted spider mite, Tetranychus urticae.

Animals

[Adult-onset neuronal ceroid lipofuscinosis--a case report with biological study].

A 32-year-old male was admitted to our hospital complaining of dementia, gait disturbance and blindness. These symptoms developed at the early two decade and were progressive. On admission, his clinical features included dementia (IQ = 69), spasticity, accentuated deep tendon reflexes, ataxia and hypesthesias in his distal limbs. Brain CT scans showed diffuse cerebral atrophy. On light microscopy, many abnormal lipopigments resembling ceroid and lipofuscin were found in Schwann cells of sural nerve and histiocytes of colon. Ultrastructurally, these materials showed lamellar structure like Zebra bodies. Nine lysosomal enzymes, serum very long-chain fatty acids, serum amino acids and urinary oligosaccharides were all normal. Neuronal ceroid lipofuscinosis (NCL) of adult type was diagnosed on the basis of clinical features, radiological and pathological findings, and biochemical studies. Many previous studies suggested that NCL was a disorder with lysosomal dysfunction. We examined lysosomal protein degradation, using 125I-low density lipoprotein (LDL) in cultured fibroblasts from this patient. The degradation of LDL was normal, compared to control subjects. The activities of cathepsin and lysosomal glycosidases, were also normal. The amount of urinary dolichol has been reported to be elevated in the patients with infantile and late infantile types of NCL. However, no elevation was found in the urine of our patient.

Adult

Endotoxin-induced uveitis in mice. 1. Induction of uveitis and role of T lymphocytes.

Endotoxin-induced uveitis (EIU) with a high frequency of posterior iris synechiae was induced by the systemic injection of 200 micrograms of endotoxin into C3H/HeN mice, an endotoxin-responsive strain. The cell number and the protein concentration within the aqueous humor began to increase 6 hours after the injection, achieving a peak at 24 hours, and decreased gradually thereafter. Inflammatory cells were observed in the anterior chamber, the vitreous body and near the iris-ciliary body histologically. Most of the inflammatory cells were polymorphonuclear cells. On the other hand, C3H/HeJ mice, an endotoxin-unresponsive strain, showed no increase in either cell number or protein concentration in the aqueous humor after endotoxin administration. Pretreatment of C3H/HeN mice with anti-Thy-1.2 antibody significantly decreased both the cell number and the protein concentration in the aqueous humor and the incidence of the posterior synechiae, as compared with the control group. Anti-CD4 antibody also significantly reduced the severity of EIU, while anti-CD8 antibody had no influence on the disease. Anti-IFN-gamma antibody increased the cell number in the aqueous humor. These observations indicate that T lymphocytes, especially CD4+ T lymphocytes, have an extremely important role in the development of EIU in mice.

Animals

[Diagnosis and management of benign biliary strictures with percutaneous transhepatic cholangioscopy (PTCS)].

From January 1981 through March 1991, we encountered twenty four cases of benign biliary strictures. In 10 cases of anastomotic stricture, percutaneous dilatation was carried out in 1 patient under fluoroscopy and in 3 patients under PTCS without recurrence. Endoprosthesis with silicone or polyurethane catheters was carried out under PTCS in 5 patients. One of them died of hepatic failure due to clogging of the catheter, and in other four patients the endoprosthetic catheter was dislodged spontaneously or removed by PTCS because of dislodgement or obstruction of the catheter, and PTCS revealed that the anastomotic stricture had improved. Reoperation of cholangiojejunostomy was carried out in 1 patient, who died of hepatic failure 5 years later due to recurrent of stricture. In 8 cases of the iatrogenic and 1 case of traumatic stricture, percutaneous dilatation was carried out (1 under fluoroscopy and 4 under PTCS) without recurrence. Cholangiojejunostomy was carried out in 3 cases without anastomotic stricture. PTCS was performed for 5 cases of the inflammatory stricture of the hepatic hilus due to cholecystitis to confirm the histological findings by cholangioscopic biopsy. And all cases could be managed by cholecystectomy. Authors recommend that PTCS should be used for the diagnosis and treatment of benign biliary stricture.

Aged

Characterization of T-cell subsets, soluble interleukin-2 receptors and interleukin-6 in Vogt-Koyanagi-Harada disease.

The lymphocyte subunits and subsets of 12 patients with Vogt-Koyanagi-Harada disease (VKH disease) were characterized using two-color flow cytometry techniques, both in cerebrospinal fluid (CSF) and in peripheral blood (PB). Soluble interleukin-2 receptor (sIL-2R) levels and interleukin-6 (IL-6) levels were also measured. The percentage of T cells was significantly higher in CSF than in PB (P less than 0.01), but the percentage of B cells was decreased in CSF (P less than 0.05). As for T-cell subsets, the percentage of helper T cells was especially high in CSF (P less than 0.01). Also, the ratio of helper T cells/suppressor T cells was significantly larger in CSF than in PB. These data suggest that helper T cells play an important role in the early stages of VKH disease. sIL-2R and IL-6 levels were not elevated in CSF of patients with VKH disease. The level of sIL-2R in serum also was not elevated.

Adult

Effects of 9-(1,3-dihydroxy-2-propoxymethyl) guanine (DHPG) eye drops and cyclosporine eye drops in the treatment of herpetic stromal keratitis in rabbits.

The effect of 9-(1,3-dihydroxy-2-propoxymethyl) guanine (ganciclovir, DHPG) eye drops and the anti-inflammatory effect of cyclosporine (CYA) eye drops on experimental herpetic stromal keratitis in rabbits with herpes simplex virus (HSV) were studied. Ten rabbits were presensitized by subcutaneous injection of HSV, type 1, on days 14 and 7 before intrastromal inoculation of the same virus. These rabbits were divided into 2 groups and treatment was started 48 hours after virus inoculation. The eye drops used were 0.1% DHPG, 0.1% CYA or the vehicles of these eye drops. Eye drops were given 5 times a day and eyes were scored every day for 3 weeks after inoculation. The right eyes of Group 1 were treated with 0.1% DHPG and 0.1% CYA eye drops, and the left eyes with 0.1% DHPG and the vehicle of CYA eye drops. The right eyes of Group 2 were treated with 0.1% CYA and the vehicle of DHPG eye drops, and the left eyes with the vehicles of CYA and DHPG eye drops. The combination of DHPG and CYA was the most effective in decreasing the severity of herpetic stromal keratitis. Treatment with DHPG alone was also effective, but CYA alone was less effective.

Administration, Topical

[Localization of bovine cornea-specific protein in mouse and human eyes].

Rats were immunized by purified bovine cornea-specific protein (CSP) and anti-CSP polyclonal antibody was produced. Localization of CSP in mice and human eyes was examined by immunohistochemical methods with light microscopy using this antibody. In mice CSP was found in the corneal epithelium, keratocytes, corneal endothelium, conjunctival epithelium and lens epithelium. In human eyes CSP was found in the corneal epithelium, keratocytes and conjunctival epithelium, but it was not found in the lens. These results confirmed a difference in localization of CSP between mice and human eyes. It was suggested that the production of CSP might be associated with phylogenesis and that CSP might also be associated with the development of the cornea.

Animals

[Endogenous uveitis in disseminated intravascular coagulation induced by endotoxin].

A study was made of endogenous uveitis in experimental disseminated intravascular coagulation (DIC) in rabbits. Endotoxin was injected intravenously twice with a 24-hour interval. The time courses of the following were examined: 1) aqueous flare using a laser flare-cell meter 2) the number of leukocytes in the peripheral blood 3) the tumor necrosis factor (TNF) activity in the serum and 4) histopathological changes in the eye, lung, liver and kidney. Aqueous flare increased at 1 hour and was maximal at 6 hours, accompanied by a rapid increase in TNF activity at 1 hour following the first endotoxin administration. The number of leukocytes decreased to 963 +/- 266 cells/mm3 at 1.5 hours with subsequent leukocytosis within 12 hours. After the second injection of endotoxin, the aqueous flare peaked in 30 minutes and was twice as high as the first peak. Leukocyte number and TNF activity showed the same behavior. However, TNF activity was 20% that of the first peak. Histopathological examination indicated fibrin formation in the small vessels of systemic organs within 3 hours following the second administration of endotoxin. Endotoxin induced uveitis was induced in experimental DIC, and leukocytes and TNF activity may thus perform important roles.

Animals

Effects of oxygen supply on protein metabolism in surgically injured rats. Oxygen as a nutrient.

The effect of various inspired oxygen concentrations on protein metabolism after surgery was investigated in rats. Surgical injury was produced by transecting the stomach. Rats were divided into three groups, i.e., a hyperoxic group, a hypoxic group, and a normoxic control group, which were supplied with 40%, 10%, and 21% oxygen, respectively, for 7 days after operation. All rats were fed intravenously (257 kcal/kg/day, kcal/N: 185.5) and whole-body protein turnover was measured using the constant infusion of 15N glycine technique developed by Picou and Taylor-Roberts. For six days after operation, the cumulative nitrogen balance was negative for the hypoxic rats, while hyperoxic rats showed a positive balance that was significantly higher than in control rats (p less than 0.01). Protein synthesis and breakdown rates increased markedly and the rate of synthesis exceeded that of breakdown in the hyperoxic group, but in the hypoxic group synthesis remained unchanged while breakdown increased moderately. These results indicate that oxygen, as a nutrient, is effective for improving postoperative protein metabolism.

Animals

Effects on herpes simplex virus type 1 of combined use of interferon-beta and anti-herpetic agents in vitro.

It has been shown that the use of interferon (IFN) alone has little or no therapeutic effect in the treatment of herpetic keratitis. However, IFN used in combination with anti-herpetic agents has high therapeutic efficacy. This interaction between IFN and anti-herpetic agents has not been elucidated clearly. In this study, the interaction between human fibroblast interferon (HuIFN-beta) and anti-herpetic agents, 5-iodo-2'-deoxyuridine (IDU), aciclovir (ACV) and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), was studied in vitro using VERO cells. After the formation of a monolayer of VERO cells, HuIFN-beta of various concentrations was added to the maintenance medium. After 24 hours incubation, the medium was removed and herpes simplex virus (HSV) type 1 was inoculated on the VERO cells. Then, anti-herpetic agents were added to the medium in various concentrations. After 48 hours incubation, plaques were counted and the reduction rate in numbers of plaque was calculated. It was found that the combination of HuIFN-beta with IDU, ACV or DHPG worked synergistically in the inhibition of HSV replication.

Acyclovir