Function of hepatic stimulatory substance-induced proliferating hepatocytes in ODS-od/od rats.
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Animals↗
Biomedical subjects
M Sawa
Publications and source records attributed to M Sawa.
Involvement of Fas and Fas ligand interaction in allogeneic hepatocyte rejection in the spleen.
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Animals↗
Critical role of Fas/Fas ligand interaction in CD28-independent pathway of allogeneic murine hepatocyte rejection.
Cytolytic induction of T cells requires both the T-cell receptor (TCR)-mediated antigenic stimulation and the CD28-mediated co-stimulatory signal. Blockade of the interactions between CD28 and its ligands, CD80 and CD86, prolongs the survival of allografts in some transplantation models. However, we found that allogeneic hepatocytes were completely rejected within 7 days after intrasplenic transplantation, even when treated with monoclonal antibodies (mAbs) against CD80 and CD86 (anti-CD80/86). Recent studies have shown that there are two main mechanisms of T-cell-mediated cytotoxicity, perforin-based and Fas-based ones. It has been shown that the liver is highly sensitive to induction of apoptosis by an agonistic anti-Fas mAb. We then investigated the role of the Fas/Fas ligand (FasL) system in the CD28-independent allogeneic hepatocyte rejection. With the anti-CD80/86 mAb treatment, hepatocytes from C57BL/6 lpr/lpr (B6 lpr) mice, which express little Fas antigen, could survive for 7 days after intrasplenic transplantation, and hepatocytes from C57BL/6 (B6) mice could also survive for 7 days in the spleen of C3H/ He gld/gld (C3H gld) mice, which express no functional FasL. CD28-independent induction of cytotoxicity against allogeneic hepatocytes was not observed when the effector cells were derived from C3H gld mice. These results indicated that the Fas/FasL system plays a critical role in the CD28-independent pathway of allogeneic hepatocyte rejection.
Animals↗
Mechanisms of lymphocyte adhesion to cultured human corneal epithelial cells.
PURPOSE: The authors studied the adhesion mechanisms between peripheral blood lymphocytes (PBL) and cultured human corneal epithelial (HCE) cells to investigate the lymphocyte interaction with corneal epithelial cells in the corneal immune response. METHODS: First, the authors examined the expression of intercellular adhesion molecule (ICAM)-1 or lymphocyte function-associated antigen (LFA)-3 on the normal human corneal epithelium and cultured HCE cells by an immunostaining technique and flow cytometry. Effects of inflammatory cytokines such as interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, on ICAM-1 or LFA-3 expression on cultured HCE cells were also examined. Second, the authors performed an adhesion assay with 51Cr-labeled monocyte-depleted PBL from normal, healthy volunteers and cultured HCE cells, with and without treatment of IFN-gamma or TNF-alpha in 96-well-plates for 1 hour at 37 degrees C in 5% CO2. After unbound PBL were removed, the radioactivity of the sample in each well was counted with a scintillation counter. In addition, the authors evaluated the blocking effects of monoclonal antibodies (mAbs) on the adhesion of PBL to the cultured HCE cells. RESULTS: ICAM-1 expression was not detected in the normal human corneal epithelium. However, the expression of ICAM-1 was detected on the cultured HCE cells with Dulbecco's Modified Eagle Medium supplemented with 10% fetal bovine serum. In addition, both IFN-gamma and TNF-alpha increased ICAM-1 expression on the cultured HCE cells dramatically. LFA-3 expression was detected in all cell layers of the normal human corneal epithelia. Neither IFN-gamma nor TNF-alpha had any effect on LFA-3 expression on the cultured HCE cells. The PBL adhesion to the HCE cells with and without treatment of IFN-gamma or TNF-alpha was blocked dominantly by anti-ICAM-1 or anti-LFA-1 alpha mAb. Anti-LFA-3 mAb also blocked the PBL adhesion but had less blocking effect than anti-ICAM-1 or anti-LFA-1 alpha mAb. Anti-very late activation antigen beta, or anti-human leukocyte antigen (HLA)-class I or HLA-class II mAb had no effect on the PBL adhesion to the HCE cells. The adhesion percentile of the PBL applied to the HCE cells pretreated with IFN-gamma or TNF-alpha showed a dose-response curve dependent on the concentration of these cytokines. CONCLUSIONS: The results in the present study demonstrate that (i) adhesion of lymphocytes to HCE cells could be mediated by the LFA-1-ICAM-1 pathway and/or the CD2-LFA-3 pathway; (ii) the LFA-1-ICAM-1 pathway could be crucial in lymphocyte adhesion to HCE cells; (iii) IFN-gamma or TNF-alpha exerts an enhancing effect not only on the ICAM-1 expression on HCE cells but also on the adhesion of lymphocytes to HCE cells.
Antibodies, Monoclonal↗
Effect of retinol palmitate as a treatment for dry eye: a cytological evaluation.
Vitamin A is known to regulate the proliferation and differentiation of corneal epithelial cells and preserved conjunctival goblet cells and has been used in the treatment of disease of the eye such as dry eye and superior limbic keratoconjunctivitis for some time. This study was undertaken in order to evaluate the efficacy of retinol palmitate aqueous ophthalmic solution under development for the treatment of dry eye failing to respond to the conventional therapy with artificial tears or cornea-protective drugs. Retinol palmitate ophthalmic solution was applied repeatedly for 4 consecutive weeks. Before and after instillation therapy, brush cytology (Cytobrush-S) was performed and cytodiagnosis was made for keratinized cells, nonkeratinized cells, goblet cells and inflammatory cells on samples prepared using an automated smear apparatus (ThinPrep). In dry eye, an increase in goblet cells (1.3+/-2.6-->2.1+/-1.8 cells/slides), a decrease in keratinized cells (11.2+/-16.5-->5.2+/-10.9 cells/300 cells) and, hence, an increase in nonkeratinized cells (287.3+/-16.6-->293.4+/-11.4/300 cells) were found after treatment with retinol palmitate. As to inflammatory cells, there was no change from the pretreatment baseline (1.4+/-1.4-->1.4+/-1.3 cells/300 cells). These results demonstrate that brush cytology suggests the efficacy of retinol palmitate ophthalmic solution in dry eye treatment.
Administration, Topical↗
Frequency characteristics of accommodation in a patient with agenesis of the posterior vermis and normal subjects.
AIMS: To clarify the cerebellar control of accommodation in humans, the frequency characteristics of accommodation were studied in a patient with agenesis of the posterior cerebellar vermis and four age matched normal subjects. METHODS: Magnetic resonance imaging of the brain of the 29 year old patient showed agenesis of the vermis and paravermis of lobules VIII-X and hypoplasia of the vermis and paravermis of lobules I-VII, the cerebellar hemisphere, and the cerebellar nuclei. The gain and phase lag of accommodative responses for sinusoidally modulated blur stimuli were calculated for the patient and four normal subjects. The blur stimuli consisted of predictable simple sinusoids of 3.0 dioptres at a frequency of 0.05, 0.1, 0.2, 0.3, 0.5, or 1.0 Hz. RESULTS: The frequency characteristics of accommodative responses in the patient have a larger phase lag and a smaller gain at higher frequencies than those in the four normal subjects. CONCLUSIONS: These findings suggest that the cerebellum contributes to the control of accommodation by improving the frequency characteristics at high frequencies.
Accommodation, Ocular↗
[Histological examination of lymphoid follicles in conjunctiva-associated lymphoid tissue in guinea pigs--Report 1. Histological characteristics of follicular dendritic cells].
We histologically examined the existence of follicular dendritic cells (FDCs) in the follicular area of conjunctiva-associated lymphoid tissue (CALT). Animals used in the experiment were Hartley guinea pigs sensitized with a topical application to the eyes of an emulsion of a mixture of ovalbumin and Freund's complete adjuvant in equal amounts. The animals were divided into 4 groups: a group with no eye drops administered (Group A), a group examined 1 week after administration of eye-drops (Group B-1), a group examined 2 weeks after administration (Group B-2), and a group given booster administration of eye-drops (Group C). These animals were examined by methyl green pyronine staining, alpha-naphthylacetate esterase staining, and enzyme-antibody methods against S-100 protein or major histocompatibility complex class II (MHC class II) antigen. Also peroxidase-anti-peroxidase (PAP) was applied to the eyes and the uptake of PAP in CALT was observed histologically. In each group, positive reticular stains to alpha-naphthyl-acetate esterase staining and S-100 protein were found in the CALT follicular area. The positive cells were found to be dendrite cells by immunoelectron microscopy. An uptake of PAP was seen in the CALT follicular area, suggesting the function of trapping and holding the antigen-antibody complex by FDCs. It was concluded that dendritic cells present in the follicular area of CALT were FDCs.
Animals↗
[Histological and ultrastructural study of corneal endothelium after excimer laser ablation in rabbit].
To investigate the effect of excimer laser ablation on the corneal endothelium in the early period, an excimer laser ablation was performed on rabbit cornea. Electron microscopy revealed an irregular space in the endothelial membrane facing Descemet's membrane 48 hours after the laser ablation. At 60 hours, electron-dense material was observed between the endothelial cells and Descemet's membrane. At 72 hours, electron-dense material was observed in Descemet's membrane, but no morphologic change was observed in the endothelium. These results suggest that excimer laser ablation may affect reversible corneal endothelium and it is important to perform a long-term follow-up of the corneal endothelium after excimer laser ablation in humans.
Animals↗
Hepatocyte transplantation: past, present and future.
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Animals↗
[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↗
The beneficial effect of dibutyryl cyclic adenosine monophosphate on warm ischemic injury of the rat liver induced by cardiac arrest.
Dibutyryl cAMP (DBcAMP) has a high membrane permeability, and maintenance of the intracellular cAMP concentration may improve the viability of organs. In this study, the effect of DBcAMP pretreatment on warm ischemic injury of rat livers was evaluated. Warm ischemic liver injury was induced in adult Wistar rats weighing 250-280 g by leaving them at room temperature (22-25 degrees C) after cardiac arrest. The hepatic cAMP concentration, %ATP, and trypan blue-positive nuclear ratio were determined after different durations of warm ischemia. In addition, transaminase and endothelin-1 (ET-1) release into the perfusate were examined during 60 min of isolated liver perfusion with Krebs-Henseleit solution. The optimal dose and time of DBcAMP pretreatment were determined to be 15 mg/kg and 60 min prior to warm ischemia, respectively. Data on the trypan blue-positive nuclear ratio and the release of transaminases and ET-1 revealed that warm ischemia first damaged the endothelial cells and then the hepatocytes. DBcAMP pretreatment appeared to protect the liver from warm ischemic injury by increasing the intracellular cAMP concentration and stabilizing the cell membranes of endothelial cells and hepatocytes.
Adenosine Triphosphate↗
Effect of hepatocyte growth factor on the proliferation of intrasplenically transplanted hepatocytes in rats.
The effect of human hepatocyte growth factor on the proliferation of intrasplenically transplanted hepatocytes was investigated. A human hepatocyte growth factor (360 micrograms/kg BW) was administered intravenously every 24 hr for 5 days following hepatocyte transplantation in rats. A significant increase in hepatocyte proliferation was observed morphologically and immunohistochemically (p < 0.05). The bromodexyuridine labeling index was significantly greater in human hepatocyte growth factor treated rats than in the control rats (p < 0.05). Hepatocyte growth factor may promote the proliferation of intrasplenically transplanted hepatocytes.
Animals↗
[An immunohistological study on a failed case of keratoepithelioplasty form alkali burn on the ocular surface].
We performed immunohistochemical study on a failed case of keratoepithelioplasty (KEP). A 33-year-old man underwent KEP with lammellar keratoplasty (LKP) for an alkali burn suffered 5 years previously. After several rejections, the cornea developed opacity. We performed surgery a second time with the same method, and investigated the removed keratoconjunctival tissue including the lenticule using enzyme labelled antibodies UCHL-1, MB-1, CD4, CD8, CD54 (ICAM-1), CD68, and HLA-DR. Conjunctival tissue extended to the lamellar corneal graft over the lenticule. Either UCHL-1, CD4, or CD8 positive lymphocytes infiltrated the subconjunctival tissue dominantly, but they were blocked by the lenticule or Bowman's membrane of the graft cornea. In the stroma of the lamellar graft cornea, CD4 or CD8 positive, ICAM-1 or HLA-DR expression cells were detected. It was concluded that the lenticule and Bowman's membrane of the lamellar graft block infiltration of the immune cells.
Adult↗
[A familial case of keratoconus with corneal granular dystrophy].
We report a familial case of keratoconus with corneal granular dystrophy. The mother and first son have both keratoconus and corneal granular dystrophy and the second son has keratoconus alone. The keratoconus in this family is thought to be an autosomal dominant or an X-linked inheritance pattern. Granular dystrophy is an autosomal dominant inheritance. This familial case suggests that the gene loci of the two diseases are close together or have a close relationship.
Adolescent↗
P element-induced mutations in Drosophila melanogaster showing high interspecific crossability between D. melanogaster females and D. simulans males.
Homozygous stocks for the second or the third chromosome of Drosophila melanogaster with a single insertional plwB element were screened for high crossability with D. simulans. Reciprocal crosses between each of these stocks and D. simulans were made, and the insemination rate at two or three days was examined. From two cycles of screening of the original 575 stocks, one stock (# 687) which showed high insemination rate was selected and was backcrossed to a w strain to substitute the background. We obtained a stock which showed 10% insemination rate with D. simulans males (control was 0%). No stocks exhibiting a high crossability with D. simulans females were acquired. Revertant strains, from which the P element had been lost, were obtained from the backcrossed # 687 stock. The insemination rates of 13 revertants to D. simulans males ranged from 1% to 33%. Seven of these 13 were not significantly different from the control line but were significantly different from the backcrossed # 687 stock. It was concluded that the mutation showing high crossability with D. simulans males was caused by the P element transposition.
Animals↗
Epistatic interactions among the P element-induced high interspecific crossability strains in Drosophila melanogaster.
Five Drosophila melanogaster strains showing high interspecific crossability with D. simulans males, derived from the previous screening of a set of autosomal plwB transposants, were selected and the effect of the plwB insertion under the same genetic background (white strain) on the interspecific crossability was examined. This phenotype was recessive in the two strains but semidominant in the other three strains. Trans-heterozygotes, however, showed high interspecific crossability compared with the parental homozygotes, suggesting some epistatic interactions between them. In three strains, the effect of the plwB insertion region in different backgrounds (w1118 strain) on the crossability was also tested. Homozygotes of a strain (#687) showed high interspecific crossability comparable to the w background, while homozygotes of both #68 and #783 strains showed lower crossability than w1118. Although #783 heterozygotes showed intermediate values between #783 homozygotes and w1118, #68 heterozygotes showed a significantly higher insemination rate than w1118 and the #68 homozygotes. These results suggest that the region around the plwB insertion sites of #68 and #783 affects the interspecific crossability either positively or negatively depending on the genetic background. In all the stocks, positive correlation between interspecific crossability and the intraspecific mating speed was detected.
Animals↗
[The time required topical carbonic anhydrase inhibitor (MK-507) to take effect on intraocular pressure of normal human eyes].
The effective time course of a topical carbonic anhydrase inhibitor, MK-507, on intraocular pressure (IOP) was studied in 6 normal volunteers. As a baseline study, IOP was determined and aqueous protein concentration was determined by laser flare photometry every half hour for 5 hours with the instillation of a placebo. Then, an examination with the same time course was performed on the same subjects with the instillation of 1% MK-507 or oral administration of acetazolamide at a dose of 250 mg. MK-507 lowered IOP 30 minutes after the instillation, and showed a significant reduction of IOP at 1 hour. Aqueous protein concentration increased significantly 30 minutes after the MK-507 instillation. Acetazolamide lowered IOP 30 minutes after the administration, and showed a significant reduction of IOP at one hour. Aqueous protein concentration increased significantly one hour after the acetazolamide administration. Corneal thickness, anterior chamber depth, anterior chamber volume, and serum protein concentration were not significantly changed by the drug treatment. These results suggest that the inhibition of aqueous humor production causes the rapid reduction of IOP seen in the use of MK-507 as well as acetazolamide.
Administration, Topical↗
[Histological study of allergic conjunctivitis--1. Study on the adhesion molecules to allergic conjunctivitis].
We performed an immunohistochemical study on the relationship between inflammatory cells and adhesion molecules to investigate inflammatory reaction in allergic conjunctivitis. Guinea pigs were sensitized with an intraperitoneal injection of ovalbumin with hydroxyalminium. Ovalbumin was applied topically to the conjunctiva 3 weeks after the initial treatment. Then the cornea, conjunctiva and lacrymal gland were taken and processed for frozen sections. The specimens were stained with acid Giemsa for inflammatory cells and enzyme-labelled antibody for ICAM-1 and VCAM-1. Neutrophils were dominantly observed 6 hours after the challenge with the antigen, eosinophils at 12 hours, and eosinophils and lymphocytes at 24 hours, respectively. ICAM-1 and VCAM-1 were detected at 6 and 24 hours in the vascular tissue in the subconjunctival tissue and lacrymal gland. There results suggest that adhesion molecules play a role in the infiltration of inflammatory cells in allergic conjunctivitis.
Animals↗