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Biomedical subjects

T Tsuru

Publications and source records attributed to T Tsuru.

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

Mechanism of concordant corneal xenograft rejection in mice: synergistic effects of anti-leukocyte function-associated antigen-1 monoclonal antibody and FK506.

BACKGROUND: The mechanisms of corneal xenogeneic immunoreaction, as well as the potential role of immunosuppressive therapy in the suppression of corneal xenograft rejection, have not been thoroughly explored. METHODS: BALB/c mice who received orthotopic corneal transplants (Lewis rats donors) were administered intraperitoneally anti-leukocyte function associated antigen-1 (LFA-1) monoclonal antibody (mAb) or FK506 (3 mg/kg/day) or both of these immunosuppressants during a 12-day postoperative period. Histological (hematoxylin-eosin stain) and immunohistochemical evaluations of enucleated eyes were performed. Humoral immune response and delayed-type hypersensitivity (ear-swelling assay) were evaluated. RESULTS: The mean (+/-SD) graft survival time in the untreated control, FK506-treated, anti-LFA-1 mAb-treated, and combined-treatment groups was 5.8+/-0.8, 9.4+/-4.0, 8.7+/-5.0, and 67.7+/-16.4 days, respectively. In the untreated control group, mouse IgG, IgM, and C3 were expressed on the rat corneal grafts during the early postoperative phase. Flow cytometry studies revealed high titers of xenoreactive IgG and IgM antibodies. T helper 1 cytokines were expressed on xenografted corneal beds, and delayed-type hypersensitivity was induced. However, local expression of IgM, C3 and T helper 1 cytokines, serum antibodies of IgG and IgM, and delayed-type hypersensitivity were suppressed in the anti-LFA-1 mAb- plus FK506-treated group. CONCLUSIONS: Both humoral and cell-mediated immune reaction play an important role in the initial rejection in rat-to-mouse corneal xenotransplantation. The treatment with anti-LFA-1 mAb in combination with FK506 synergistically suppresses concordant corneal xenogeneic reaction.

Animals↗
PubMed1997

Anterior chamber inoculation of splenocytes without Fas/Fas-ligand interaction primes for a delayed-type hypersensitivity response rather than inducing anterior chamber-associated immune deviation.

The inoculation of antigens into the anterior chamber (AC) of the eye induces an antigen-specific immune response that inhibits delayed-type hypersensitivity (DTH). This regulatory response is known as anterior chamber-associated immune deviation (ACAID). The ACAID response appears to be complex, as it can be elicited by a wide variety of soluble and cell-associated antigens, including foreign, self, tumor, and alloantigens. To evaluate the contribution of Fas/Fas ligand (FasL) interaction to the induction of ACAID to alloantigens, gld and lpr mutant mice were used in conjunction with normal C3H, MRL, and BALB/c mice. ACAID was induced by inoculation of non-irradiated splenocytes from donor mice into the AC of various recipients. After 1 week, recipients were primed intradermally with donor splenocytes. One week later DTH was measured by ear swelling. C3Hgld mutants lacking functional FasL did not develop ACAID after the AC inoculation of BALB/c splenocytes. Conversely, the AC inoculation sensitized these mutants. MRL/pr mutants, which lack Fas, developed ACAID following inoculation of BALB/c cells. AC inoculation of lpr splenocytes did not induce ACAID, but sensitized C3H recipients. Treatment of the AC inoculum with an anti-Fas antibody blocked ACAID induction in a transient manner, as the recipients developed ACAID later. These results show that interaction of the Fas and FasL is required to induce ACAID to allogeneic cells. In the absence of Fas expression on donor splenocytes, or FasL expression by the recipient, AC inoculation primes for a DTH response rather than inducing ACAID.

Animals↗
PubMed1997

Specific immunosuppression of corneal allograft rejection by combination of anti-VLA-4 and anti-LFA-1 monoclonal antibodies in mice.

It has been reported that allograft rejection is mediated by a variety of adhesion molecules. Using a corneal allograft model in mice, we studied the role of very late antigen (VLA)-4 and leukocyte function-associated antigen (LFA)-1 adhesion molecules in corneal allograft rejection and the effects of monoclonal antibodies (mAbs) to them in suppressing corneal rejection. C3H/He donor corneas were transplanted into BALB/c corneal beds. The allografted mice were treated with a control mAb (M18/2), mAbs to VLA-4, or LFA-1 or their combination by i.p. injection until day 7. The expression of VLA-4, LFA-1, major histocompatibility complex (MHC) class II antigens, interleukin (IL)-2, IL-2 receptor and interferon gamma (IFNgamma) in the grafted cornea were studied immunohistochemically. Cytotoxic T lymphocyte (CTL) responses to donor alloantigens were assessed. The skins from a syngeneic donor or a third-part strain were transplanted 8 weeks after the initial keratoplasty onto the mice treated with anti-LFA-1 plus anti-VLA-4 mAbs. Fourteen of 16 allografts in non-treated mice and control mAb-treated mice became opaque by 2 weeks after transplantation. At 2 weeks, non-treated allografts showed expression of MHC class II antigens on keratocytes and mononuclear cells at the host-graft junction. Also, mononuclear cells expressing VLA-4, LFA-1, IL-2, IL-2 receptor and IFNgammawere present in the stroma at the host-graft junction. The allografts treated with either anti-VLA-4 or anti-LFA-1 alone, or anti-VLA-4 plus anti-LFA-1 remained transparent for more than 2 weeks, and the survival rates at 14 weeks was 0%, 16.7%, and 75.0%, respectively. The combined use of anti-VLA-4 and anti-LFA-1 mAbs prolonged graft survival significantly (P<0.05) at 14 weeks as compared with anti-LFA-1 mAb alone. At 3 weeks, CTL responses to donor alloantigens were depressed in mice treated with either anti-LFA-1 alone or anti-LFA-1 plus anti-VLA-4. Specific prolongation of donor-syngeneic skin was observed after treatment with the combination of these two mAbs. These results indicate that VLA-4 and LFA-1 have important roles in rejection process of corneal allografts, and that the combined use of mAbs to these molecules has remarkable effects on inducing alloantigen-specific immunosuppression in corneal transplantation.

Animals↗
PubMed1997

[Effects of topical corticosteroids on subepithelial haze after excimer laser corneal surgery--objective and quantitative method for evaluating haze].

To examine the effectiveness of topical corticosteroids in decreasing subepithelial haze induced by excimer laser keratectomy, we performed excimer laser keratectomy on 24 eyes of 12 albino rabbits using a scanning excimer laser system (EC-5000, NIDEK, Japan). Topical dexamethasone 0.1% was applied topically to 8 corneas after surgery (steroid group), but not to the others (control group). Slit-lamp biomicroscopic examination and objective measurement of scattered light from subepithelial haze were performed before and 2, 4, 8 and 12 weeks after surgery, the rabbits were killed after 2 or 12 weeks and the eyes were examined histologically. In both groups, densitometric values of scattered light intensity increased up to 4 weeks after surgery, and then decreased gradually. However, the values of the steroid group were larger than those of the control group at all stages, and the values of the steroid group at 12 weeks after surgery were similar to preoperative values. There was statistically significant difference in scattered light intensity between the two groups (p < 0.005). Two weeks after surgery, the corneas of the control group showed epithelial hyperplasia and a remarkable increase in activated keratocytes and subepithelial fibrous tissues. However, in the steroid group these light microscopic findings could not be observed. At 12 weeks after surgery, the corneas of the control group retained a small amount of activated keratocytes and fibrous tissues, and those of the steroid group were normal. This study suggests that a short course of topical corticosteroids may be very effective in decreasing subepithelial haze after excimer laser corneal surgery.

Administration, Topical↗
PubMed1997

C5a induces tissue factor activity on endothelial cells.

Tissue factor (TF) is an integral membrane glycoprotein that serves as a cofactor for blood coagulation factor VIIa. The induction of TF on the surface of endothelial cells is initiated by various stimuli including lipopolysaccharide, interleukin-1 beta, and tumor necrosis factor alpha. We have demonstrated that recombinant human C5a induces TF activity in a dose-dependent fashion in human umbilical vein endothelial cells (HUVEC). Peak activity (4.9-fold increase) was obtained 3-6 h after treatment with 10 microM C5a. TF mRNA as assessed by RT-PCR method was also significantly increased (3.75-fold) after 3 h incubation with C5a, suggesting that C5a induces TF activity on HUVEC, at least in part, by enhancing the level of TF mRNA. The increase in TF activity by C5a was inhibited by methylprednisolone. The induction of TF on endothelial cells by C5a may represent one of many potential interrelationships between the inflammatory and coagulation schemes.

Blood Coagulation↗
PubMed1996

The role of cell adhesion molecules in allograft rejection after penetrating keratoplasty in mice. Clinical and immunohistochemical study.

BACKGROUND: It has been reported that adhesion molecules play an important role in immunological rejection after organ transplantation. In the present study, we examined the role of ICAM-1/ LFA-1 adhesion molecules in corneal allograft rejection and evaluated the immunological specificity of monoclonal antibodies (mAbs) in preventing allograft rejection in mice. METHODS: The allografted mice were intraperitoneally injected with 100 micrograms/day of the following mAbs: a control mAb, anti-ICAM-1 mAb, anti-LFA-1 mAb, or a mixture of anti-ICAM-1 and anti-LFA-1 mAbs from 1 day before to 7 days after surgery. The expression of ICAM-1 and LFA-1 molecules in the grafted cornea was studied immunohistochemically. The corneas from a syngeneic donor or a third-party strain were transplanted 4 weeks after the initial keratoplasty onto the mice treated with both anti-ICAM-1 and anti-LFA-1 mAbs. RESULTS: The allografts treated with anti-LFA-1 mAb alone or both anti-ICAM-1 and anti-LFA-1 mAbs remained transparent for more than 2 weeks, and the survival rate at 8 weeks was 40% in both groups. ICAM-1 was expressed on the mononuclear cells, keratocytes and endothelial cells in the allografts without treatment. The second corneal grafts syngeneic to the initial donor remained transparent at 2 weeks, whereas those from the third party were rejected. CONCLUSIONS: ICAM-1 and LFA-1 adhesion molecules play a crucial role in the pathophysiology of corneal transplant rejection. The immunosuppressive effects of anti-ICAM-1 and anti-LFA-1 mAbs are highly allospecific. The administration of mAbs to the adhesion molecules represents a new means of suppressing allograft rejection after penetrating keratoplasty.

Animals↗
PubMed1996

Electrical conductivity of tear fluid in healthy persons and keratoconjunctivitis sicca patients measured by a flexible conductimetric sensor.

BACKGROUND: It is known that the osmolarity of tears increases in keratoconjunctivitis sicca (KCS) patients and therefore could be a sensitive and specific indicator for the diagnosis of KCS. However, owing to the difficulties in using the current methods of tear fluid measurement these procedures have not been employed in clinical practice. A newly devised flexible conductimetric sensor fabricated using microelectronic techniques is small and flexible enough to be placed on the ocular surface to measure the electrical conductivity can be considered as an indirect function of electrolyte activity, or osmolarity. Therefore, we applied this new sensor to measure the tear fluid conductivity in KCS patients and healthy volunteers. METHODS: A flexible conductimetric sensor, consisting of a hydrophilic polytetrafluoroethylene membrane placed between two gold-coated layers, was placed directly into the temporal conjunctival cul-de-sac. The tear fluid conductivity was monitored graphically on a computer display. The sodium chloride concentration of tear fluids was calculated from the calibration curve and converted to the equivalent electrolyte concentration. RESULTS: The electrolyte concentrations were 324.8 +/- 41.0 mEq/1 in KCS patients (29 samples obtained from 16 KCS patients) and 296.4 +/- 30.1 mEq/1 in healthy persons (33 samples obtained from 17 healthy persons). The difference was significant (P < 0.01). A positive correlation was found between the electrolyte concentrations in KCS and the rose bengal score (coefficient = 0.36). CONCLUSION: The tear fluid conductivity in healthy persons and KCS patients could be monitored without ocular damage, and the measured values were consistent with previous reports. This method will be a new diagnostic tool for detecting tear abnormalities.

Adult↗
PubMed1996

Risk factors for graft failure in penetrating keratoplasty.

We clarified the preoperative risk factors for graft failure in penetrating keratoplasty with fresh donor corneas. This analysis covered 698 consecutive keratoplasty cases in a single center between 1971 and 1992, and was designed to assess the risk factors. The risk factors in penetrating keratoplasty were determined by the Cox multiple regression model which considers the follow-up periods and multiple factors simultaneously. The factors which worsen the prognosis of keratoplasty significantly were found to be preoperative endothelial dysfunction (hazard ratio = 2.3), prior glaucoma/ocular hypertension (hazard ratio = 2.0), preoperative corneal vascularization (hazard ratio for within one quadrant = 1.3, hazard ratio for 2 or more quadrants = 1.6), anterior synechiae of iris (hazard ratio = 1.5), aphakia or pseudophakia (hazard ratio = 1.4), and older donor age (hazard ratio = 1.3 in proportion to the increase of each 10-year period of age). Surgeons must take these risk factors into consideration to obtain a better prognosis for keratoplasty.

Adult↗
PubMed1996

[Allo-cytotoxic T lymphocyte responses in corneal allografted mice treated with monoclonal antibodies to adhesion molecules].

Corneal transplantation was performed by grafting C3H/He donor corneas into BALB/c corneal beds. The allografted mice were injected either with 0.5 mg/day of anti-very late antigen (VLA)-4 antibody, anti-leukocyte function-associated antigen (LFA)-1 antibody, or 0.25 mg/day each of both antibodies on days -2, 0, 1, 3, 5, and 7. After 3 weeks, cytotoxic T lymphocyte (CTL) responses to donor alloantigens were assessed. Splenocytes in the allografted mice without treatment demonstrated greater CTL responses that those in naive mice. CTL responses were depressed in mice treated with either anti-LFA-1 alone or a combination of anti-LFA-1 and anti-VLA-4 antibodies as compared with splenocytes from allografted mice without treatment. These data suggest that CTLs play significant roles in eliciting immune response to corneal allografts.

Animals↗
PubMed1995

Urinary C4 excretion in systemic lupus erythematosus.

The fourth component of complement (C4) in urine was measured in 19 patients with systemic lupus erythematosus (SLE). Urinary C4 was detectable in all SLE patients using an enzyme linked immunosorbent assay. In 11 of 13 patients whose urinary C4 was serially measured, a decrease of urinary C4 was found in parallel with a decrease of disease activity of SLE. In the remaining 2 patients, the amount of C4 increased preceding a flare-up of the disease. The measurement of urinary C4 may be useful in evaluating the disease activity of SLE in individual patients and sometimes in predicting the flare-up of the disease. The specific hemolytic activity of excreted C4 and Western blotting analysis showed that urinary C4 consisted mainly of degraded fragments of C4. In two cases, camostat, a serine protease inhibitor, rapidly decreased the urinary C4 excretion, suggesting that the complement activation occurred in the glomerulus in lupus nephritis.

Adolescent↗
PubMed1995

[Quantitative analyses of glycosaminoglycans in tear fluids in normal human eyes and eyes with corneal epithelial disorders].

The existence and pathophysiological role of glycosaminoglycans in the tear fluid in humans was investigated using quantitative analyses of hyaluronic acid and chondroitin sulfate in the tear fluid. The subjects were 42 eyes of 31 normal controls, 9 eyes of 9 patients with superficial punctate keratitis (SPK), and 13 eyes of 13 patients with epithelial defect. After an instillation of 100 microliters saline solution in the conjunctival sac, as much tear fluid as possible was collected from the lower cul-de-sac. The glycosaminoglycans in the tears were then treated with chondroitinase ABC to make fractions of unsaturated disaccharides. The quantities of disaccharides were determined by high-performance liquid chromatography. Concentrations were expressed as nanomoles of unsaturated disaccharides per protein in the tears. The concentrations of hyaluronic acid and chondroitin sulfate in the normal controls were 0.07 +/- 0.12(n mol/mg protein) and 6.91 +/- 3.63 (n mol/mg protein), respectively. The mean concentration of hyaluronic acid was significantly higher in patients with epithelial erosion than in normal controls, whereas the mean concentration of chondroitin sulfate was significantly lower in patients with epithelial erosion than in normal controls. There was no significant difference in the concentration of glycosaminoglycans between the patients with SPK and normal controls. The results of our study suggest that glycosaminoglycans are synthesized and endogenously secreted into the tear fluids and, especially in the case of hyaluronic acid, may play an important role in corneal epithelial wound healing in patients with epithelial erosion.

Adult↗
PubMed1995

[Experimental studies on influence of alignment errors on measurement in a corneal topographic system--relationship between degree of measurement error and working distance].

To evaluate the influence of alignment errors in focusing on the results of measurements in corneal topography, we experimented using polymethyl-methacrylate balls with definite radii of curvature as test objects. We used 3 different corneal topographic systems with different working distances to clarify the relationship between the degree of errors and the working distance. We determined the refractive power of the test balls by the topographic systems and studied changes in the values as the balls were slightly displaced from the alignment position axially, or horizontally. The test balls were set on the stage with a micrometer so that the distance of displacement could be determined precisely. When the test balls were placed precisely in alignment, there was no significant relationship in the magnitude of measurement errors with working distance of the topographical systems. When the test balls were displaced axially, the measurement values decreased as the balls come near from the alignment position and increased as they moved away from the alignment position. The magnitude of the measurement errors caused by back and forth displacement of the object became larger as the working distance of the topographic system became shorter. There was no specific relationship between the degree of measurement errors and the working distance when the balls were displaced horizontally.

Cornea↗
PubMed1995

[Effects of blowing or aspiration on ablation rate by excimer laser].

Accurate calibration of ablation rate by excimer laser prerequisite for precise photorefractive keratectomy (PRK). When a polymethylmethacrylate (PMMA) plate is ablated by excimer laser, debris is generated, which may affect homogeneity of the laser beam and energy density, and change the ablation rate. In order to clarify the effects of the debris on the ablation rate, we studied the changes in the ablation rate when the debris was removed by blowing or aspirating over the ablation area during PRK.PMMA plates were ablated using a scanning excimer laser system (EC-5000, NIDEK, Japan) in PRK mode under the following conditions: (1) with air blowing over the ablation area, (2) with aspiration of the debris, and (3) without treatment. The ablation rates were determined by measuring the refractive power of PMMA plates with a lens meter. The ablated surface was observed by scanning electron microscope (SEM). The ablation rate with blowing was the highest among the three conditions, that with aspiration was the second, and that without treatment was the lowest. The ablation rates with blowing showed no significant change when the ablation rates were changed. However, the ablation rates with aspiration or without treatment decreased as the pulse rate increased. The surface ablated during blowing was the smoothest in SEM photographs. We concluded that calibration of the ablation rate using PMMA plates must be done with appropriate air blowing.

Calibration↗