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Biomedical subjects

I Ono

Publications and source records attributed to I Ono.

At least 55 records · Page 3Linked to original sources
PubMed1997

The mode of action of prostaglandin (PG) I1 analog, SM-10906, on fibroblasts of hypertrophic scars is similar to PGE1 in its potential role of preventing scar formation.

The effects of prostaglandin (PG) I1 analog, SM-10906 (SM-6) and PGE1 on extracellular matrix formation and the release of cytokines by cultured normal human dermal fibroblasts (NDF) and hypertrophic scar fibroblasts (HSF) were compared in order to evaluate the clinical efficacy of PGs in preventing scar formation. In the present study, we measured type I collagen synthesis, collagenase activity, production of interleukin (IL)-6, IL-8, and transforming growth factor (TGF)-beta 1 and levels of adenosine 3,5-cyclic monophosphate (cAMP) in NDF and HSF cultured with or without PGs. The results demonstrated that HSF culture supernatants has a significantly higher level of type I collagen and TGF-beta 1 than those of NDF. However, the levels of collagenase activity and IL-8 in HSF were significantly lower in comparison to that of NDF. There was no substantial difference in IL-6 production between two types of culture cells. On the other hand, PGE1 and SM-6 significantly enhanced collagenase activity and raised the collagenase/type I collagen ratio in the HSF supernatants. In addition, both PGE1 and SM-6 increased production of TGF-beta 1, IL-8 and IL-6 and levels of cAMP in both cell types. However, they had no effect on the type I collagen synthesis of either types. These results suggest that, the stable PGI1 analog, SM-6, similarly acts as PGE1 in HSF by increasing the activity of collagenase.

Adolescent↗
PubMed1997

Enhancement by bFGF of osteogenesis induced by rhBMP-2 in rats.

Subcutaneous implantation of bone morphogenetic protein (BMP) combined with a fibrous glass membrane (FGM) induces cartilage formation in the entire inner area of the membrane within 2 wk. It has been hypothesized that a tight FGM network (1 microm exclusion size) provides immature cells with spaces for penetrating into the membrane, but not for vascular formation, at least until 2 wk. To test this hypothesis, basic fibroblast growth factor (bFGF), known to be a potent stimulant of capillary formation, was applied to the implant. BMP was combined with FGM in the presence or absence of bFGF, and then implanted subcutaneously into the backs of rats. The bFGF-supplemented implant caused 1.3 times higher alkaline phosphatase activity and 3 times higher calcium contents at 2 wk, whereas type II collagen contents decreased, thus indicating that bFGF enhances bone formation in BMP/FGM implants. These results suggest that bFGF induces faster and stronger invasion of capillaries into the FGM and destroys its tight network, resulting in acceleration of the ossification process.

Alkaline Phosphatase↗
PubMed1997

Tissue reconstruction of gynecologic tumor cells in the rotation culture system.

Tissue reconstruction of various kinds of gynecologic malignant tumor cell lines was studied using the rotation-culture system. The reconstructed cell aggregates were examined histologically using both light and electron microscopy. Our established cell lines used in this study were uterine cervical epidermoid carcinoma, endometrial adenocarcinoma, ovarian malignant tumor and uterine sarcoma. All of the reconstructed aggregates from each cell line were very similar to the original tumor tissue. In the case of a well differentiated type of adenocarcinoma derived from the ovarian cancers or the endometrial cancers, papillary cell aggregates (grape-like structures) and/or hollow cell ball (gland alveolus-like) structures were observed. The individual cells were adjoined with by desmosomes and well developed microvilli protruded from the free surface of the cells. On the other hand large cell non-keratinizing squamous cell carcinoma cells formed spherical-shaped aggregates that showed a stratified structure similar to pearl formation. Sarcoma cells formed solid clusters while desmosomes or desmosome-like junctions were not detected. Rotation culture is an excellent method to reveal diagnosis of the original tumor and tumorigenesis by investigating a reconstructed tissue from peritoneal effusions because the reconstructed tissue is similar to the original tumor.

Adenocarcinoma↗
PubMed1997

Histogenesis of hollow cell ball structure of ovarian and endometrial adenocarcinoma cells in vivo and in vitro.

Hollow cell ball structure is often found in the ascites of adenocarcinoma patients. How to form a hollow cell ball structure was studied in vivo and in vitro, using the human cell lines derived from ovarian and endometrial adenocarcinomas. The hollow cell ball structure was formed by horizontal rotation culture of 1 x 10(7) single-suspended cells for 24 hours or by transplanting 1 x 10(6) single-suspended cells into the peritoneal cavity of nude mouse for 24 hours. At one month after transplantation hemi-cyst and hollow cell ball structure were formed in the outermost layer of the grafted tumor on the intraperitoneal serous membrane in the nude mouse. And also great number of floating hollow cell ball structure in the ascites were observed. These results suggest that mechanisms of formation of hollow cell ball structure found in the ascites; one by cell aggregate of single cells, sometimes inner cells of cell aggregate fall into necrosis or secretes mucus inside and make a hollow cell ball structure and another by the removed as the hollow cell ball structure grown from hemi-cyst on the surface of intraperitoneal grafted tumor.

Adenocarcinoma↗
PubMed1996

Determination of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine in human plasma by solid-phase extraction and column-switching high-performance liquid chromatography with ultraviolet detection.

A column-switching high-performance liquid chromatography method with ultraviolet detection at 210 nm has been developed for the determination of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine (AY4166, I) in human plasma. Plasma samples were prepared by solid-phase extraction with Sep-Pak Light tC18, followed by HPLC. The calibration graph for I was linear in the range 0.1-20 micrograms/ml. The limit of quantitation of I, in plasma, was 0.05 microgram/ml. The recovery of spiked I (0.5 microgram/ml) to drug-free plasma was over 92% and the relative standard deviation of spiked I (0.5 microgram/ml) compared to drug-free plasma was 4.3% (n = 8).

Chromatography, High Pressure Liquid↗
PubMed1996

Clinical effectiveness of an ointment containing prostaglandin E1 for the treatment of burn wounds.

This report discusses the effectiveness of conservative treatment of burns using applications of prostaglandin E1 (PGE1) containing ointment (PGE1 ointment) to the wound site. Fourteen patients with superficial dermal burns (SDB), deep dermal burns (DDB) and full-thickness dermal burns (DB), who were treated with repeated applications of this ointment, showed rapid epithelialization of the affected tissue. Hypertrophic scarring after epithelialization was less than that expected after other therapies. The degree of scarring was graded as 'none', 'mild', 'moderate' or 'severe'. The results of this therapy revealed no scarring in two sites (8.7 per cent), mild scarring in 16 sites (69.6 per cent), moderate scarring in one site (4.3 per cent) and severe scarring in four sites (17.4 per cent) out of 23 sites distributed among the patients. The application of PGE1 ointment in combination with skin grafting surgery was found to improve functional and aesthetic results in the patients with DDB and DB, by minimizing the area of the donor site; it was especially useful for children with extensive burns because of the shortage of available tissue as donor site material for skin grafting.

Administration, Topical↗
PubMed1996

Structure determination of metabolites isolated from urine and bile after administration of AY4166, a novel D-phenylalanine-derivative hypoglycemic agent.

Molecular structures of 10 metabolites, which were isolated from urine (M1-M8) or bile (M9 and M10) after administration of AY4166 (N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine), a novel amino acid derivative with hypoglycemic activity, have been elucidated by mass spectrometry and nuclear magnetic resonance. Four of these (M1, M2, M3 and M8) were determined to be hydroxyl derivatives of AY4166, two (M9 and M10) were carboxylate derivatives via oxidization of M2 and M3, three (M4, M5 and M6) were glucronic acid conjugates and the other (M7) was a dehydro derivative. The estimated structures for M1, M2, M3, M7, M8, M9 and M10 were confirmed by the coincidence of the retention time of HPLC, MS and 1H NMR spectra between the isolated metabolites and authentic synthesized substances. For three glucronic acid conjugates, M4, M5 and M6, structural confirmation was performed by a selective enzymatic digestion with beta-glucronidase. M1 and M2/3 were about 5-6 and 3 times less potent than AY4166, respectively, and M7 was almost as potent as AY4166.

Animals↗
PubMed1996

An operation for Stahl's ear.

We devised an operation to correct Stahl's ear, a rare but difficult to treat auricular malformation. First, a wedge excision is made of the anterior skin and cartilage of the abnormal, third crus prominence. The abnormal, flat part of the helix is excised. A conchal cartilage graft is used to support the area after closure of the defect, including advancement of the helical edges. The procedure has been used in five cases with satisfactory results.

Child, Preschool↗
PubMed1996

Promotion of the osteogenetic activity of recombinant human bone morphogenetic protein by prostaglandin E1.

We investigated the promotive effect of prostaglandin (PG) E1 on the osteogenetic activity of bone morphogenetic protein (BMP) using porous chemically synthesized hydroxyapatite ceramic (HAP) pellets as the carrier. After treating the pellets with recombinant human (rh) BMP-2 with or without PGE1, both of which were used at two different concentrations, they were inserted beneath the cranial periosteum of a rabbit. The degree of osteogenesis and osteoconductivity was then examined histopathologically as well as by means of an image-analyzing procedure. Results showed that there was extensive bone formation around the pellets as early as 3 weeks after insertion in the group, which received pellets treated with a relatively large amount of rhBMP alone as well as in the group receiving pellets treated with a small amount of rhBMP combined with PGE1. In the later group, the extent of bone formation was dose-dependent. Subsequent osteogenesis within the pores of the pellets in these groups slowly progressed over time, and by 9 weeks after the insertion, most of the pellet pores had filled with newly generated bone. In addition, the groups which received pellets treated with PGE1 alone also showed osteogenesis as demonstrated by osteoconduction, which was not observed in the group that received the phosphate buffered saline (PBS) treated pellets. The group that received pellets treated with a small amount of rhBMP plus a high concentration of PGE1 exhibited significantly greater bone induction than the group which received the pellets treated with a small amount rhBMP alone, and there was no statistically significant difference between the former group and the group that received a high rhBMP dose. These results clearly indicated that PGE1 has a strong and dose-dependent promotive effect on the osteogenetic activity of rhBMP and that it also promotes osteoconduction, even when used alone. This suggests that enormous reductions can be made in the amount of rhBMP administered when PGE1 is used in conjunction with porous HAP. This should prove to be very advantageous and practical in the clinical application of these materials.

Alprostadil↗
PubMed1996

Promotion of the osteogenetic activity of recombinant human bone morphogenetic protein by basic fibroblast growth factor.

In this study, we investigated the promotive effect of basic fibroblast growth factor (bFGF) on the osteogenetic activity of bone morphogenetic protein (BMP) used in conjunction with porous hydroxyapatite ceramic pellets. Results showed that there was extensive bone formation as early as 3 weeks after insertion in the group that received pellets treated with a relatively large amount of recombinant human (rh) BMP alone as well as in the group in which pellets were treated with a small amount of rhBMP combined with rhbFGF. Subsequently, osteogenesis within the pores of the pellets of the two groups slowly progressed over time; by 9 weeks after insertion, most of the pellet pores were filled with newly generated bone. In contrast, the group that received pellets treated with rhbFGF alone showed little osteogenesis, as was the case with the control group. The group that received the pellets treated with the small amount of rhBMP as well as the rhbFGF group exhibited significantly greater bone induction than the group that received the pellets treated with the small amount of rhBMP alone. These results indicated that a very small amount of rhbFGF has a strong promotive effect on the osteogenetic activity of rhBMP.

Analysis of Variance↗
PubMed1996

[CD26/dipeptidyl peptidase IV and thyroid peroxidase as molecular markers for differentiated thyroid carcinoma].

Differential expression of two enzymes, dipeptidyl peptidase IV (CD26/DPP IV) and thyroid peroxidase (TPO), in neoplastic thyroid tissues was studied by Northern blot analysis and histochemical analysis using 31 thyroid tissue specimens of various thyroid diseases. On Northern blot analysis, all 16 differentiated carcinomas (12 papillary and 4 follicular carcinomas) overexpressed CD26/DPP IV mRNA, whereas all 14 benign tissue specimens (4 normal thyroid, 4 Graves' disease, 2 adenomatous goiters and 4 follicular adenomas) showed faint expression of CD26/DPP IV mRNA. All 14 benign tissues expressed high levels of TPO mRNA, whereas all 12 papillary carcinomas strongly underexpressed TPO mRNA. A medullary carcinoma did not show any mRNA expression of either enzyme. TPO mRNA expression in differentiated carcinomas did not always correlate with mRNA expression of thyroglobulin, thyroid stimulating hormone receptor, and thyroid transcription factor-1. Northern blot analysis also revealed that CD26/DPP IV is a more specific marker of differentiated carcinoma than three proto-oncogenes previously reported to increase mRNA expression in thyroid carcinomas: c-met, c-erbB-2, and EGF-R. Histochemically, all 14 benign tissues were CD26/DPP IV negative and strongly TPO positive, while all 12 papillary carcinomas were strongly CD26/DPP IV positive and TPO negative. Three of 4 follicular carcinomas were histochemically positive for the two enzymes. These findings suggest that the differential expression of these two enzymes can be applied to study the thyroid tumorigenesis.

Adenocarcinoma, Follicular↗
PubMed1995

Determination of amino acids in human plasma by liquid chromatography with postcolumn ninhydrin derivatization using a hydroxyapatite cartridge for precolumn deproteination.

Amino acids in human plasma were determined by liquid chromatography with postcolumn ninhydrin derivatization using a hydroxyapatite cartridge for precolumn deproteination. S-Carboxymethyl-L-cysteine, D-phenylglycine and S-aminoethyl-L-cysteine were found to be suitable internal standards. The proposed method is simple, rapid (deproteination time less than 1 min) and reproducible [relative standard deviation below 3% except for low-level aspartic acid (n = 3)]. The average recovery of 25 amino acids was above 90%. The elution time of amino acids in human plasma was approximately 2 h. Protein binding of tryptophan was also determined by the proposed method. The analytical data for amino acids in human plasma deproteinated using the proposed and published methods (5-sulphosalicylic acid and ethanol) were compared.

Amino Acids↗
PubMed1995

Prostaglandin I1 analogues, SM-10902 and SM-10906, affect human keratinocytes and fibroblasts in vitro in a manner similar to PGE1: therapeutic potential for wound healing.

The newly synthesized prostaglandin (PG) I1 analogues, SM-10902 and SM-10906, were compared with PGE1 in terms of their biological effects on cultured normal human keratinocytes (NHKs) and human dermal fibroblasts (HDFs) in order to evaluate their therapeutic potential for cutaneous wound healing. The PGI1 analogues had a direct effect on cell proliferation of HDFs as did PGE1, but inhibited cell growth of NHKs in contrast to the stimulatory effect observed with PGE1. In contrast to NHKs stimulated with PGI1 analogues, which exhibited low levels of adenosine 3,5-cyclic monophosphate (cAMP). HDFs stimulated with these analogues responded in a dose-dependent manner with extremely high levels of cAMP. Conditioned media (CM) derived from media in which HDFs had been incubated with both the PGI1 analogues promoted NHK proliferation. HDF production of interleukin (IL)-6 increased in response to the PGI1 analogues. Since IL-6 was shown to promote cell growth of NHKs, enhancement of NHK proliferation by CM was thought to be due to IL-6 derived from HDFs stimulated with the PGI1 analogues.

Alprostadil↗
PubMed1995

A study of cytokines in burn blister fluid related to wound healing.

This report indicates that retention fluid from blisters of partial skin thickness burns, which contains relatively large amounts of cytokines and growth factors, stimulates the wound healing process. Although epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) levels were low, relatively large amounts of cytokines including platelet derived growth factor (PDGF), interleukin (IL-6) and transforming growth factor (TGF) alpha were present and these exercised stimulatory effects on wound healing. TGF beta, which plays an important role in collagen metabolism and in scar formation, was also detected. Contrary to our expectations, IL-1 alpha and beta, both of which initiate inflammation, were detected at relatively low levels whereas IL-8 levels were rather high. Various cytokines were shown to coexist in a balanced state in the retention fluids, suggesting that epithelialization might be regulated via a cytokine network operating on the wound surface. The growth of keratinocytes in culture significantly increased with the addition of 1 per cent or more of blister fluid to the medium.

Blister↗
PubMed1995

Studies on cytokines related to wound healing in donor site wound fluid.

This study was performed to evaluate cytokines in donor-site wound fluids and to determine their effect on wound healing. A film dressing was applied to the donor-site wound of 24 patients immediately after a split-thickness skin graft was taken. On the 5th day after treatment, 2-3 ml of the fluid retained under the film dressing was collected by means of puncture with a syringe. Growth factors and cytokines considered to accelerate wound healing were present in relatively large amounts in the exudate. Very low concentrations of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) were detected by a commercially-available enzyme-linked immunosorbant assay (ELISA) kit. However, the presence of both growth factors in wound fluid could not be confirmed because of the possible cross-reactivity of the antibodies to other EGF and FGF family growth factors. In contrast, platelet derived growth factor (PDGF), interleukin-6 (IL-6), transforming growth factor-alpha (TGF-alpha) and TGF-beta were present in relatively large amounts. The finding that certain cytokines coexist in a balanced state under the film dressing suggests that epithelization can proceed, since an adequate balance would insure proper regulation by the cytokine network. Our present study increases the likelihood that film or hydrocolloid dressings will be used more frequently in the future for treatment of burn wounds, ulcers or donor-site wounds since these dressings were shown to be more capable than ointments of retaining cytokines, particularly intrinsic growth factors secreted at the wound site.

Adult↗
PubMed1995

Efficacy of hydroxyapatite ceramic as a carrier for recombinant human bone morphogenetic protein.

In this study, we investigated the efficacy of hydroxyapatite ceramic (HAP) as a carrier of bone morphogenetic protein (BMP) using porous HAP pellets artificially fabricated from limestone. After treatment with recombinant human BMP-2, the pellets were inserted beneath the cranial periosteum of rabbits, and the degree of osteogenesis was examined histologically. The degree of osteogenesis was also evaluated using image-analyzing procedures. Results showed that extensive bone formation had occurred around the pellets 3 weeks after insertion in the group that received pellets treated with recombinant human BMP alone as well as in the group that received recombinant human BMP in addition to type I collagen-treated HAP pellets. Subsequently, osteogenesis within the pellets slowly progressed over time, and by 9 weeks after insertion most of the pellet pores in both groups were filled with newly generated bone. The recombinant human BMP-collagen group, however, exhibited a significantly greater bone induction. These results indicated that if recombinant human BMP is used clinically in the future, artificially fabricated HAP would be a suitable carrier.

Analysis of Variance↗
PubMed1995

Pneumocephalus caused by fistulas of the mastoid air cells treated with a temporoparietal fascial flap.

Using a temporoparietal fascial flap and hydroxyapatite ceramics, we treated a patient for complications after a neurosurgical operation for glossopharyngeal neuralgia. These consisted of pneumocephalus and cerebrospinal fluid rhinorrhea resulting from fistulas of mastoid air cells associated with a subcutaneous dead space. By means of the temporoparietal fascial flap, we were able to fill the dead space and reinforce the repaired dural and mastoid lesion as well. Hydroxyapatite ceramics were also useful for closing the mastoid air cell fistulas.

Bone Diseases↗