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Biomedical subjects

I Tobari

Publications and source records attributed to I Tobari.

At least 19 recordsLinked to original sources

[Effect of different concentrations of tranilast on posterior capsule opacification].

PURPOSE: To evaluate the effect of different concentrations(0.5, 1.0, 2.0%) of tranilast eyedrops in preventing fibrous posterior capsule opacification (PCO) in rabbits. METHODS: Experimental phacoemulsification procedures and in-the-bag placement of intraocular lens(IOL) implant were performed. An anterior eye segment analysis system(EAS-1000, Nidek Co, Ltd) was used to evaluate the degree of PCO during 5 weeks after surgery. RESULTS: The development of PCO was significantly suppressed in the eyes treated with tranilast eyedrops from 1 week after surgery. The mean PCO density after treatment with 0.5% tranilast was 59.1 +/- 9.3 (mean deviation +/- standard error) and 57.1 +/- 8.2, while for 1.0% tranilast it was 40.1 +/- 6.8 and 46.6 +/- 8.4, and for 2.0% tranilast it was 38.5 +/- 6.0 and 37.5 +/- 5.6 (computer compatible tape, CCT) at 1 week and 5 weeks, respectively. In the control group, the mean PCO density was 89.3 +/- 10.4 and 137.4 +/- 32.8 at 1 week and 5 weeks, respectively(p < 0.05). However, no significant statistical difference was observed in any of the findings for the 3 different tranilast concentrations. CONCLUSION: These results suggest that the 0.5% tranilast eyedrops, which are already available on the market, are sufficiently effective for inhibiting PCO.

Animals↗

Effect of tranilast eyedrops in preventing posterior capsule opacification: preliminary report.

PURPOSE: To evaluate the effect of tranilast eyedrops in preventing fibrous opacification of the posterior lens capsule after cataract extraction and intraocular lens (IOL) implantation. SETTING: The Second Department of Ophthalmology, Toho University School of Medicine, Tokyo, and Shohzankai Medical Foundation, Miyake Eye Hospital, Nagoya, Japan. METHODS: This study comprised eyes having continuous curvilinear capsulorhexis and phacoemulsification/aspiration followed by implantation of a posterior chamber IOL in the capsular bag. In this prospective, randomized, controlled, and double-masked trial, tranilast 0.5% (Rizaben) eyedrops (15 eyes) or its placebo eyedrops (20 eyes) were given 4 times a day for 3 months after surgery. An anterior eye segment analysis system (EAS 1000, Nidek Co., Ltd.) was used to evaluate the degree of fibrous posterior capsule opacification (PCO) 1 week and 1 and 3 months after surgery. RESULTS: The mean PCO density in the tranilast group was 17.1 cct +/- 4.6 (SD), 20.0 +/- 3.6 cct, and 23.0 +/- 7.7 cct (cct = computer compatible tape) at 1 week and 1 and 3 months, respectively. In the control group, it was 18.2 +/- 5.3, 30.2 +/- 7.8, and 38.4 +/- 8.0 cct, respectively. There was a significant difference in the 1 and 3 month findings between the 2 groups (P < .001). CONCLUSION: Tranilast was effective in preventing fibrous PCO at an early postoperative stage. The possible mechanisms of its effect may be prevention of collagen synthesis by minimizing transforming growth factor type beta released during lens epithelial cell metaplasia.

Aged↗

Effects of transforming growth factor beta on corneal epithelial and stromal cell function in a rat wound healing model after excimer laser keratectomy.

BACKGROUND: Transforming growth factor beta (TGF-beta) regulates extracellular matrix deposition, cell proliferation, and migration, and is expressed in cornea. TGF-beta is thought to be involved in the corneal wound healing process. METHODS: The central corneal area (3 mm in diameter) of Lewis rats was ablated using PTK mode excimer laser and the wound healing process was observed at 12 and 24 h and 2, 5, 10, and 30 days after treatment. The expression of TGF-beta 1, -beta 2 and -beta 3, TGF-beta type I and type II receptors, alpha 3, alpha 5, beta 4 integrin subunits, laminin and fibronectin was studied immunohistochemically. Antibody neutralizing TGF-beta 1, -beta 2 and -beta 3 was administered intraperitoneally, 50 micrograms daily, for 5 days after the laser treatment to investigate the effects of TGF-beta function blockade. RESULTS: At the leading edge of the regenerating epithelium, no TGF-beta type I and type II receptors and beta 4 integrin subunits were expressed after 24 h. Regenerating epithelium covered the ablated area after 2 days. An abnormal fibrotic layer was formed in the subepithelial area. This layer contained round-shaped cells in the stroma in the early stage (2-5 days after laser ablation) and spindle-shaped fibroblast-like keratocytes after 10 days. Laminin and fibronectin expression increased in the fibrotic layer. The increased stromal cells expressed TGF-beta isoforms and TGF-beta receptors. Neutralizing TGF-beta inhibited the stromal cell increase in the laser ablated area after 5 days. CONCLUSION: TGF-beta may be involved in epithelial cell migration and stromal cell reaction during the corneal wound healing process after excimer laser ablation in rat models.

Activin Receptors, Type I↗

[A case of retinochoroidal optic neuropathy].

The patient was a 59-year-old male with impaired left vision. Before he was referred to this hospital, he was diagnosed as having optic nerve injury due to the trauma of a severe bruise on his left eye caused by a traffic accident, and relative afferent pupillary defect (RAPD) was negative. On his first examination in this department, RAPD was negative and funduscopy of the left eye demonstrated hyperemia of the optic disc and mild opacification at the posterior pole. Fluorescein fundus angiography showed circular hyperfluorescence around the optic disc and transverse linear hyperfluorescence appearing above and below the macula. From these findings a diagnosis of choloidal rupture was made. The form of choloidal rupture suggested an early stage of evulsion of the optic nerve. The impairment of visual acuity seemed to be caused by choloidal circulatory disturbance. The patient was therefore, had traumatic retinocholoidal optic neuropathy complicated by the rupture of the choloidal around the optic disc, disturbance of the optic disc, and opacification of the retinochoroid.

Accidents, Traffic↗

[Functions of the transforming growth factor-beta superfamily in eyes].

One human body is composed of 6 x 10(13) cells, and eyes are also composed of many cells of different functions. The cellular functions and intercellular interaction are regulated by many regulators including cytokines and growth factors to maintain the homeostasis. The transforming growth factor-beta (TGF-beta) superfamily, a large family of multifunctional factors, regulates various cellular functions, including cellular proliferation, migration, differentiation, apoptosis and extracellular matrix production. The TGF-beta superfamily contains about 30 multifunctional factors, and is divided into several families according to the sequence homology. The TGF-beta family, the activin family, and bone morphogenic proteins belong to the TGF-beta superfamily. TGF-beta superfamily members transduce signals through type I and type II serine/threonine type transmembrane receptors. The signals are transduced from receptors through nuclei by Smad family members, which are phosphorylated by the activated type I receptors and translocate from cytoplasm into nuclei. TGF-beta family members and the TGF-beta superfamily receptor family are expressed in ocular tissues including the cornea, ciliary epithelium, lens epithelium, retina, and blood vessels. This observation suggests the importance of the TGF-beta superfamily in eyes. Smad family members (Smad 1, Smad 2, Smad 3 and Smad 4) are expressed in the cultured retinal pigmant epithelial cell line (D407), in which TGF-beta and activin A stimulate the translocation of Smad 2, but not Smad 1 into nuclei, whereas bone morphogenetic protein (BMP) stimulates that of Smad 1, but not Smad 2. TGF-beta superfamily members play important roles in the pathogenesis of retinal neovascularization and in the wound healing process of corneal tissue. TGF-beta inhibits the endothelial functions, but, stimulates angiogenesis in vivo. TGF-beta is involved in the formation of abnormal connective tissue in corneal wound healing. In these processes, many cytokines and growth factors are involved, interacting with each other and forming networks. It is mandatory to clarify the networks to investigate molecular pathogenesis and new therapeutic agents.

Diabetic Retinopathy↗

Radiosensitivity and effects of repair inhibitors for X-ray-induced chromosomal damage in mouse zygotes in S and G2 phases.

The potentiation effects of arabinofuranosyl cytosine (ara-C), hydroxyurea, 3-aminobenzamide, and caffeine on the yield of chromosome aberrations were examined at the first-cleavage metaphase in mouse zygotes irradiated with X-rays in S and G2 phases (7.5 and 12 h after insemination respectively) in vitro. Potentiation effects were found in both S and G2 for all chemicals except ara-C. Caffeine completely released G2 arrest, which was not overcome by any other chemicals, and enhanced chromosome aberrations most effectively. Caffeine enhanced chromosome aberrations more in G2 irradiation than in S irradiation, and the frequency of chromatid-type aberrations was remarkably enhanced in G2 irradiation. The results in this study demonstrated an existence of two types of caffeine effects in the mouse zygotes irradiated in S and G2; a cancellation of G2 arrest and direct inhibition of DNA repair pathways. The chromosomal damage induced in G2 was effectively repaired by a repair pathway, which is affected by caffeine, on the other hand, the progression of cell cycle, not repair inhibition, was a major factor of caffeine effect on the yield of chromosome aberrations in S irradiation.

Animals↗

Postoperative cellular reaction on surface modified intraocular lenses in living human eyes.

Specular microscopy was performed to evaluate the postoperative cellular reaction on surface modified poly(methyl methacrylate) intraocular lenses (IOLs) (Ioptex Research, Inc., model U370) in 40 eyes of 36 patients who had extracapsular cataract extraction with implantation of the surface modified IOLs. The cellular elements observed were fibroblast-like cells, histiocytes, and giant cells. Gray amorphous depositions, part of which were sometimes recognized as interference fringes or interference colors, formed a layer in the center of the optics. These depositions were probably caused by the adsorption from aqueous humor. In subclinical cases, only a few histiocytes and giant cells were recognized in the optic center and the optic periphery was free of the cells during our observation. Within two months of surgery most of the cells had disappeared. In vivo specular microscopy showed no manufacturing defects on the implanted lenses. Our findings suggest that, although there was a postoperative cellular reaction on the surface modified IOLs, they were biocompatible.

Aged↗

Repair capacity of fertilized mouse eggs for X-ray damage induced in sperm and mature oocytes.

To study the repair capacity of fertilized mouse eggs for X-ray damage induced in sperm and mature oocytes, the potentiating effects of 3 well-known repair inhibitors, arabinofuranosyl cytosine (ara-C), 3-aminobenzamide (3AB) and caffeine, on the frequency of induced chromosome aberrations were examined in eggs fertilized with X-irradiated sperm or in eggs irradiated with X-rays at the mature oocyte stage immediately before fertilization. Gametic treatment, fertilization and embryo culture were carried out in vitro. Ara-C treatment was done only in the pre-DNA replication period, while treatment with 3AB and caffeine was continuous from fertilization to the first-cleavage metaphase. The induction of chromosome aberrations by exposing sperm or oocytes to X-rays was remarkably potentiated by post-treatment incubation in the presence of each of the 3 inhibitors. This result indicates the possibility that X-ray damage induced in sperm or oocytes is reparable in the fertilized eggs and that various types of repair processes are involved.

Animals↗

X-ray- and mitomycin C (MMC)-induced chromosome aberrations in spermiogenic germ cells and the repair capacity of mouse eggs for the X-ray and MMC damage.

Chromosome aberrations induced at the first-cleavage metaphase of eggs fertilized with sperm recovered from spermiogenic cells which had been X-irradiated and treated with mitomycin C (MMC) at various stages were observed using in vitro fertilization and embryo culture technique. Furthermore, the repair capacity of the fertilized eggs for X-ray- and MMC-induced DNA damage which was induced in the spermiogenic cells and retained in the sperm until fertilization was investigated by analysis of the potentiation effects of 2 repair inhibitors, 3-aminobenzamide (3AB) and caffeine on the yield of chromosome aberrations. The frequency of chromosome aberrations observed in the eggs fertilized with sperm recovered from the early spermatid to late spermatocyte stage with X-irradiation of 4 Gy (16-20 days after X-irradiation) was markedly higher than that in the eggs fertilized with sperm recovered from spermatozoa to late spermatid stage (0-8 days after X-irradiation). The induced chromosome aberrations predominantly consisted of chromosome-type aberrations, the main type being chromosome fragment followed by chromosome exchange through all the spermiogenic stages. On the other hand, a high frequency of chromosome aberrations was not induced through all the stages with MMC treatment of 5 mg/kg. The remarkable potentiation effects of 3AB and caffeine were found in the eggs fertilized with sperm recovered from almost all the spermiogenic stages after X-irradiation. In the MMC treatment, a remarkable caffeine effect was observed occasionally in mid-early spermatids to late spermatocytes where a large amount of MMC damage could be induced. These results suggest that the large amount of DNA lesions induced in spermiogenic cells by X-rays and MMC persist as reparable damage until sperm maturation and are effectively repaired in the cytoplasm of the fertilized eggs.

Animals↗

Mechanism of chromosome aberration induction in the mouse egg fertilized with sperm recovered from postmeiotic germ cells treated with methyl methanesulfonate.

Chromosome aberrations induced in spermatozoa to late spermatocytes following treatment with methyl methanesulfonate (MMS) were examined at the first-cleavage metaphase of fertilized eggs in an attempt to clarify the mechanism of chromosomal damage in postmeiotic germ cells. A high frequency of chromosome aberrations was induced in early spermatozoa to mid spermatids, while few chromosome aberrations were observed in early spermatids to late spermatocytes. 3-Aminobenzamide (3AB) potentiated the effect of MMS-induced chromosome aberrations in spermatozoa to mid spermatids indicating that a large amount of DNA lesions produced at these stages during spermatogenesis were not repaired prior to fertilization of the oocytes. Furthermore, from the cell-cycle analysis of the repair capacity in the fertilized egg it became clear that the lesions which remained in sperm until fertilization could be divided into 2 types: (1) DNA-strand breaks induced by stress in the chromatin structure produced by protamine alkylation; these lesions were converted to chromosome-type aberrations by 3AB treatment of the eggs during G1 phase; and (2) alkylated DNA which produces apurinic or apyrimidinic sites, of which there were a significant number mainly converted to chromatid exchanges by 3AB treatment of the eggs during S phase. This type of lesion appears to be constantly induced through all spermiogenic stages in contrast to the former type of lesion which is induced specifically during the stage of protamine maturation.

Animals↗

Changes in X-ray sensitivity of mouse eggs from fertilization to the early pronuclear stage, and their repair capacity.

To study the changes in radiosensitivity of male and female genomes from fertilization to the pronuclear stage, the frequency of induced chromosome aberrations was examined at the first-cleavage metaphase in eggs fertilized with X-irradiated sperm, in eggs X-irradiated at the mature oocyte stage immediately before fertilization, and in fertilized eggs exposed to X-rays at various stages before DNA synthesis (1-5 h after insemination). Gametic treatment, fertilization and embryo culture were carried out in vitro. Most of the induced chromosome aberrations were chromosome-type aberrations, the frequency of chromosome fragments being the highest, followed by chromosome exchanges in both sperm and oocytes. The induction of chromosome-type aberrations was much higher in oocytes than in sperm. Chromosome-type aberrations were the main type also in fertilized eggs irradiated at the pre-DNA-synthetic stage. The radiosensitivity increased gradually with pronuclear formation (1-4h after insemination), but little difference in radiosensitivity was observed between eggs irradiated at 4 h and 5 h, corresponding to the stage when pronuclear formation was complete. The drastic change with pronuclear formation was found not only in radiosensitivity but also in the frequency of chromosome aberrations. The frequency of chromosome-type exchanges decreased drastically 2 h after insemination, and exchanges were barely observed at 5 h. The difference in radiosensitivity between male and female genomes also markedly changed with pronuclear formation, the chromosome aberration induction in the female genome being much higher than that in the male genome before accomplishment of pronuclear formation. The analysis of potentiation effects of 3-aminobenzamide and caffeine on the yield of X-ray-induced chromosome aberrations demonstrated that the increase of radiosensitivity and the decrease of chromosome-type exchange induction with pronuclear formation, may be closely correlated with alterations in chromatin configuration in the pronuclei and in repair capacity of fertilized eggs at the pre-DNA-synthetic stage. No evidence based on repair efficiency was found for the marked difference in radiosensitivity between male and female genomes during pronuclear formation.

Animals↗

Relationship between cell cycle stage in the fertilized egg of mice and repair capacity for X-ray-induced damage in the sperm.

The potentiation effects of 3-aminobenzamide, caffeine, hydroxyurea and arabinofuranosyl cytosine on the yield of X-ray-induced chromosome aberrations of mouse sperm were examined at the first-cleavage metaphase, to clarify a correlation between chromosome aberrations and cell cycle dependency of repair capacity of the fertilized egg. The result provided evidence that there are two major types of DNA damage in X-irradiated sperm: (1) short-lived DNA lesions; the lesions are subject to repair inhibition by agents added in G1 and are converted into chromosome-type aberrations during G1, and (2) long-lived DNA lesions; the lesions persist until S phase and repair of the lesions is inhibited by caffeine, hydroxyurea and arabinofuranosyl cytosine in G2.

Animals↗

Chromosomal analysis in mouse eggs fertilized in vitro with sperm exposed to ultraviolet light (UV) and methyl and ethyl methanesulfonate (MMS and EMS).

Chromosome aberrations were analyzed at the first-cleavage metaphase of mouse eggs fertilized in vitro with sperm exposed to ultraviolet light (UV) as well as to methyl and ethyl methanesulfonate (MMS and EMS). The frequencies of chromosome aberrations markedly increased with dose of UV as well as with concentration of MMS and EMS. In the UV-irradiation group, the frequency of chromosome-type aberrations was much higher than that of chromatid-type aberrations. About 90% of chromosome aberrations observed in the eggs following MMS and EMS treatment to sperm were chromosome type in which the frequency of chromosome fragments was the highest. The effects of UV on the induction of chromosome aberrations were clearly potentiated by post-treatment incubation of fertilized eggs in the presence of Ara-C or caffeine, but the effects of MMS and EMS were not pronounced by post-treatment of Ara-C or caffeine. The results indicate a possibility that UV damage induced in mouse sperm DNA is reparable in the eggs during the period between the entry of sperm into the egg cytoplasm and the first-cleavage metaphase.

Animals↗

Dose-response relationship for translocation induction in spermatogonia of the crab-eating monkey (Macaca fascicularis) by chronic gamma-ray-irradiation.

The induction of reciprocal translocations in spermatogonia of the crab-eating monkey (Macaca fascicularis) by chronic gamma-irradiation (1.8 x 10(-5) Gy/min, about 0.024 Gy/22 h/day) was examined. The frequencies of translocation per cell were 0.15% at 0.3 Gy, 0.27% at 1.0 Gy and 0.33% at 1.5 Gy. The dose-response relationship for translocation yield was a linear one with a regression coefficient (b) of 0.16 x 10(-2). When the slope (b) of the regression line was compared with that at a high dose rate (0.25 Gy/min, b = 1.79 x 10(-2), it was clear that the induction rate of translocations after chronic gamma-irradiation was only about one-tenth of that after high-dose-rate irradiation. Thus, there was evidence for a pronounced dose-rate effect in the crab-eating monkey.

Animals↗