Biomedical subjects

K Tsubota

Publications and source records attributed to K Tsubota.

At least 37 records · Page 2Linked to original sources

PubMed2002

Improvement of corneal fluorescein staining in post cataract surgery of diabetic patients by an oral aldose reductase inhibitor, ONO-2235.

AIM: While the mechanism in the pathogenesis of diabetic corneal disease is unclear, aldose reductase has been implicated in corneal disease. The effects of an oral aldose reductase inhibitor (ARI) on the ocular surface of diabetic patients after cataract surgery were studied. METHODS: This clinical trial was designed to be randomised, double blinded, and placebo controlled. Pseudophakic patients with diabetes were randomly assigned to treatment with either oral ARI (ONO-2235) (n=12) or placebo (n=9) for 12 weeks. The vital staining of the ocular surface, tear production and clearance, break up time in tears (BUT), corneal and conjunctival sensation, and symptom score before treatments were examined as well as 4, 8, 12 weeks after the administration. Specular microscopic evaluation was also performed. RESULTS: After a 12 week period of oral ARI administration, fluorescein staining scores (from 2.04 (SD 1.12) to 1.46 (1.18); p=0.016), conjunctival sensation (from 1.15 (0.37) to 1.36 (0.31); p=0.0006), and symptom scores (from 5.38 (1.932) to 4.00 (2.07); p=0.0002) recovered significantly. Fluorescein staining of oral ARI administration also decreased compared with placebo (p=0.017). Rose bengal staining, tear clearance, and corneal sensation were improved although this increase was minor. Tear production, BUT, and specular microscopic evaluation of the corneal epithelium and endothelium did not demonstrate a significant change. CONCLUSION: Oral ARI opposes the ocular surface changes caused by diabetes, by recovery of ocular surface sensitivity as demonstrated through an improvement in vital staining.

Administration, Oral↗

PubMed2001

Possible involvement of EBV-mediated alpha-fodrin cleavage for organ-specific autoantigen in Sjogren's syndrome.

A cleavage product of alpha-fodrin may be an important organ-specific autoantigen in the pathogenesis of Sjogren's syndrome (SS), but the mechanisms of alpha-fodrin cleavage remain unclear. Since EBV has been implicated in the pathogenesis of SS, we determined whether EBV activation could induce the SS-specific 120-kDa autoantigen alpha-fodrin. ZEBRA mRNA expression, a marker for activation of the lytic cycle of EBV, was found in the salivary gland tissues from SS patients, but not in those from control individuals. ZEBRA-expressing lymphoid cells were also found in the SS glands in double-stained immunohistochemistry. Furthermore, a significant link between production of Abs against 120-kDa alpha-fodrin and reactivated EBV Ag was found in sera from patients with SS, but not in those from control individuals. EBV-activated lymphoid cells showed specific alpha-fodrin cleavage to the expected 120-kDa fragments in vitro. Pretreatment with caspase inhibitors inhibited cleavage of alpha-fodrin. Thus, an increase in apoptotic protease activities induced by EBV reactivation may be involved in the progression of alpha-fodrin proteolysis in the development of SS.

Amino Acid Chloromethyl Ketones↗

PubMed2001

Defective cellular trafficking of lacrimal gland aquaporin-5 in Sjögren's syndrome.

Dry eyes and dry mouth are clinical hallmarks of Sjögren's syndrome. We assessed the distribution of aquaporin-5 (AQP5) in lacrimal gland biopsy samples. Healthy controls and patients with Mikulicz's disease or non-Sjögren's syndrome dry eye had the expected apical distribution of AQP5 in lacrimal acinar cells. By contrast, cytoplasmic AQP5 was seen in patients with Sjögren's syndrome. Sodium channel and sodium-potassium ATPase distributions were normal in all groups. These findings show a selective defect in lacrimal gland AQP5 trafficking in Sjögren's syndrome that might contribute to decreased lacrimation and dry eye in these patients.

Aquaporin 5↗

PubMed2001

Laser in situ keratomileusis: association with increased width of palpebral fissure.

PURPOSE: To report the preoperative and postoperative palpebral fissure width in eyes undergoing laser in situ keratomileusis. METHODS: In a prospective study, 165 consecutive eyes of 87 patients (41 men and 46 women with a mean +/- standard deviation age of 32.9 (+/-9.5) years) had laser in situ keratomileusis using a Summit (Waltham, MA) APEX PLUS excimer laser and a Moria (Antony, France) LSK microkeratome. The width of palpebral fissure was measured preoperatively, 3 months or 6 months after laser in situ keratomileusis. Patients were classified into three groups as follows: hard contact lens users group (n = 61), soft contact lens users group (n = 63), and non-contact lens users group (n = 41). RESULTS: The average width of palpebral fissure increased after laser in situ keratomileusis in all three groups. The hard contact lens users group increased from 7.6 (+/-1.6) mm to 8.7 (+/-1.2) mm (P <.0001) and non-contact lens users group increased from 7.7 (+/-1.9) mm to 8.9 (+/-1.9) mm (P <.0001). CONCLUSION: These results suggest that laser in situ keratomileusis may be associated with an increase in the width of the palpebral fissure.

Adult↗

PubMed2001

Multilayered amniotic membrane transplantation for severe ulceration of the cornea and sclera.

PURPOSE: To examine the efficacy of amniotic membrane transplantation in the treatment of deep corneal and scleral ulcers. PATIENTS: A total of 11 patients were recruited for this study: four patients (four eyes) with corneal perforation, five patients (five eyes) with a deep corneal ulcer and descemetocele, and two patients (two eyes) with a scleral ulcer. METHODS: Ulcers were treated by amniotic membrane transplantation. Separate amniotic membranes were transplanted as material to fill the stromal layer (amniotic membrane filling), as a basement membrane (amniotic membrane graft), and as a wound cover (amniotic membrane patch). After surgery, all cases were treated with artificial tears, autologous serum drops, antibiotic eyedrops, topical corticosteroids, and sodium hyaluronate eyedrops. RESULTS: Eight eyes (72.7%) healed with epithelialization in 16.5 +/- 8.0 days (range, 7 to 29 days), with five and three eyes showing corneal epithelialization and conjunctival epithelialization, respectively. A persistent epithelial defect was noted in one eye with corneal ulcer after limbal allograft transplantation for a chemical burn and in two eyes with corneal ulcers as a complication of rheumatoid arthritis. CONCLUSION: Multilayered amniotic membrane transplantation may be effective for the treatment of deep ulceration of the cornea and sclera. In some eyes with total corneal limbal dysfunction or autoimmune disorders, amniotic membrane transplantation alone is not effective.

Administration, Topical↗

PubMed2001

Dry eye after laser in situ keratomileusis.

PURPOSE: To determine whether patients undergoing laser in situ keratomileusis have postoperative dry eye. METHODS: In this retrospective, interventional case series, 124 eyes of 64 consecutive patients who underwent laser in situ keratomileusis were examined for a dry eye symptom, Schirmer test with anesthesia, tear clearance rate, tear break-up time, vital staining for ocular surface, corneal sensitivity, and blink rate. All values were compared before and after surgery (1 month, 3 months, 6 months, and 1 year) and values of P <.05 were considered statistically significant. RESULTS: Subjective score for dryness was increased after laser in situ keratomileusis. Tear function index (Schirmer value/tear clearance rate) and break-up time were decreased until 1 month (tear function index) and 3 months (break-up time) after laser in situ keratomileusis but recovered to preoperative levels thereafter. Fluorescein and rose bengal scores were unchanged at all follow-up points except for improvement of the rose bengal score at 6 months. Corneal sensitivity was decreased at 1 month and 3 months, and returned to the preoperative level at 6 months after laser in situ keratomileusis. Blink rate was decreased at 3 months, 6 months, and 1 year after laser in situ keratomileusis. CONCLUSIONS: Patients undergoing laser in situ keratomileusis develop dry eye with compromised tear function for at least 1 month after surgery. Use of artificial tears in the early postoperative period may help to prevent unwanted symptoms and ocular surface damage.

Adult↗

PubMed2001

Effect of laser in situ keratomileusis correction on contrast visual acuity.

PURPOSE: To evaluate the changes in contrast visual acuity (CVA) based on the amount of myopic correction with laser in situ keratomileusis (LASIK). METHODS: In this prospective study, patients with myopia ranging from -2.0 to -14.0 diopters (D) were divided into 2 groups: those with myopia less than -6.0 D (n = 20) and those with myopia greater than -6.0 D (n = 13). The CVA was measured preoperatively and 1 week and 1 and 3 months postoperatively using Variable Contrast Visual Acuity Charts. RESULTS: The patients with less than -6.0 D of myopia had a CVA decrease of 15% 1 week postoperatively, which recovered by 1 month, and a decrease of 2.5% 1 week and 1 month postoperatively, which recovered by 3 months. The patients with more than -6.0 D of myopia had a decrease of 15% and 2.5% at all postoperative times. CONCLUSIONS: After LASIK to correct myopia of greater than -6.0 D, there may be a persistent decrease in intermediate and low CVA. Patients should be informed preoperatively of this possible decrease in CVA.

Adult↗

PubMed2001

Allergic conjunctivitis as a risk factor for laser in situ keratomileusis.

PURPOSE: To analyze the effect of allergic conjunctivitis (AC) on the outcome of laser in situ keratomileusis (LASIK) in myopic eyes. SETTING: Minamiaoyama Eye Clinic, Tokyo, Japan. METHODS: Patients who had LASIK were divided into 2 groups: those with AC (84 eyes of 49 patients; the allergic group) and those without AC (140 eyes of 77 patients; the nonallergic group). Allergic conjunctivitis was diagnosed clinically by symptoms of eye itching and clinical findings such as papillary proliferation on the tarsal conjunctiva. Preoperative and postoperative uncorrected visual acuity (UCVA) and refraction and intraoperative and postoperative complications were compared. RESULTS: There were no significant differences in UCVA and refraction between the 2 groups. No complications were observed in the allergic group. Intraoperative conjunctival chemosis (3 eyes of 2 patients) and a postoperative epithelial defect that resulted in epithelial ingrowth (1 eye) were observed in the nonallergic group. CONCLUSION: The findings suggest that AC is not a risk factor for LASIK.

Adult↗

PubMed2001

Suppressive effect of locally produced interleukin-10 on respiratory syncytial virus infection.

Interleukin (IL)-10 is known to be a multifunctional cytokine. This study was designed to evaluate the role of IL-10 during respiratory syncytial virus (RSV) infection using a C57BL/6 transgenic (TG) mouse model in which the expression of murine IL-10 cDNA was regulated by a human salivary amylase promoter (IL-10 TG mice). These mice expressed a large amount of IL-10 in the nasal mucosa and in salivary glands. Viral replication in the respiratory tract after intranasal infection with RSV was suppressed significantly in IL-10 TG mice compared to non-transgenic controls. This suppression was IL-10 specific, because it was prevented by treating mice with neutralizing anti-IL-10 antibodies. We also found that IL-10-stimulated T cells displayed cytotoxic activity against infected murine nasal epithelial cells. Previous data indicated that IL-10 induces Fas ligand (L) expression on mouse T cells. Taken together, these data suggest that Fas/Fas L mediated cytotoxicity is involved in the suppression of RSV replication observed in IL-10 TG mice after intranasal infection.

Animals↗

PubMed2001

Immunologic rejection of the central graft after limbal allograft transplantation combined with penetrating keratoplasty.

PURPOSE: To study the incidence and prognosis of immunologic rejection of the central graft after limbal allograft transplantation (keratolimbal allograft transplantation [KLAT]) combined with penetrating keratoplasty (PKP). METHODS: Endothelial rejection in central penetrating graft after simultaneous KLAT and PKP using the same donor cornea was retrospectively studied. Incidence, reversibility, prognosis, and changes in limbal grafts were examined. RESULTS: Forty-five eyes underwent simultaneous PKP and KLAT. Endothelial rejection of the central graft was found in 16 eyes (35.6%). At last examination, 10 grafts (62.5%) restored clarity after immunosuppressive therapy. During rejection episodes, four eyes showed engorgement of vessels in limbal grafts, which existed before the episodes. Only one eye developed neovascularization with mild edema of the limbal grafts; however, no other limbal grafts showed abnormalities on biomicroscopy. No epithelial changes were noted, and 14 grafts (87.5%) were covered by corneal epithelium after the rejection. CONCLUSION: Approximately one third of eyes had endothelial rejection in the central graft after simultaneous KLAT and PKP. Abnormalities suggestive of rejection in the limbal grafts were seldom observed in these eyes, suggesting that immunologic response was different in central and limbal grafts.

Adult↗

PubMed2001

Quantitative evaluation of atopic blepharitis by scoring of eyelid conditions and measuring the water content of the skin and evaporation from the eyelid surface.

PURPOSE: To quantitatively evaluate the condition of the eyelid skin of patients with atopic blepharitis, their symptoms were scored and the water content of the skin and evaporation from the skin were measured. METHODS: Forty patients with atopic blepharitis were examined. The condition of eyelid skin (erythema, edema/papulation/oozing/crust, excoriation/lichenification) was scored from 0 to 3 points. Water content and water evaporation were measured with a Moisture Checker and an evaporimeter, respectively. Eleven age-matched volunteers without atopic disorders were recruited as normal controls. RESULTS: The Moisture Checker values and water evaporation from lid skin were significantly correlated (r = -0.44, p = 0.006). The Moisture Checker values of the patients with atopic blepharitis was 35.5+/-8.2% (44.7 +/-10.6% in the normal controls, p = 0.009), and water evaporation from their lid skin was 3.6+/-0.9 g/cm2 per second (2.0+/-0.3 g/cm2 per second, p < 0.001); then, the patients were divided into four groups, from "asymptomatic" to "severe," according to the sum of their blepharitis scores. Patients with lower blepharitis scores tended to have higher Moisture Checker values and lower water evaporation values. CONCLUSION: Scoring of eyelid condition enabled us to objectively estimate the severity of atopic blepharitis. Measurements of the water content of lid skin and water evaporation from lid skin are useful in evaluation of the severity of this disease.

Adolescent↗

PubMed2001

Antiinflammatory effects of amniotic membrane transplantation in ocular surface disorders.

PURPOSE: To determine whether the sequestration of inflammatory cells plays a role in the antiinflammatory effects of amniotic membrane transplantation to the ocular surface. METHODS: Amniotic membrane grafts were prepared from placental tissue procured from mothers undergoing planned Cesarean sections. A detailed explanation was given to all donors, and a written consent was obtained before processing. Amniotic membrane tissue was dissected into 3- x 3-cm segments, rinsed in phosphate buffered saline, and stored in dimethyl sulfoxide solutions at -80 degrees C until use. In a clinical series, amniotic membrane patches of the ocular surface were performed in 20 eyes of 20 patients with persistent corneal epithelial defects, or as a prophylactic measure after corneal limbal transplantation. Amniotic membrane patches were harvested after a 1-week observation period and were subjected to histopathologic examinations by hematoxylin and eosin staining. Inflammatory cells trapped within the amniotic membrane were labeled by immunocytochemistry using anti-CD14, CD4, CD8, and CD20 antibodies. TUNEL (TdT-mediated dUTP nick end labeling) staining was done to observe cells undergoing apoptosis. The T cell line Molt 4 was co-cultured with amniotic membrane in vitro to observe adhesion of T cells to amniotic membrane. RESULTS: Various degrees of inflammatory cell infiltration were observed in all clinical samples of amniotic membrane patches. Most of the inflammatory cells stained positively with anti-CD14 antibodies, indicating that these cells were of monocyte/macrophage lineage. Subsets of T cells included both CD4(+) and CD8(+) cells, whereas CD20(+) cells were sparse. TUNEL assays revealed that trapped inflammatory cells exhibited characteristics of cells undergoing apoptosis. Molt 4 invaded within amniotic membrane in an in vitro assay, which was not inhibited by blocking antibodies to beta1 and beta2 integrins. CONCLUSION: Amniotic membrane attracts and traps inflammatory cells infiltrating the ocular surface, which may explain some of the antiinflammatory properties of the fetal tissue.

Amnion↗

PubMed2001

Successful treatment of dry eye in two patients with chronic graft-versus-host disease with systemic administration of FK506 and corticosteroids.

PURPOSE: We present two cases of severe dry eye in patients with chronic graft-versus-host disease (CGVHD) after hematopoietic stem cell transplantation (SCT) who were successfully treated by the systemic administration of FK506 and corticosteroids. METHODS AND RESULTS: A 29-year-old man with chronic myelogenous leukemia underwent SCT. Oral and lung CGVHD developed on approximately day 130, and dry eye associated with CGVHD was diagnosed on day 168. The patient began receiving cyclosporin A (150 mg/d) for the treatment of oral and lung CGVHD. Treatment with prednisolone (1 mg/kg/d) began on approximately day 300. Oral and lung GVHD improved slightly, but worsened again although systemic administration of cyclosporin A and prednisolone were continued. Cyclosporin A was discontinued, and systemic administration of FK506 was started on day 376. Forty-four days later, marked improvement in the ocular surface and other organs was observed. However, the dry eye worsened while tapering FK506, with no flare of other affected organs. A 43-year-old woman with myelodysplastic syndrome underwent SCT. She received FK506 for prophylaxis of CGVHD. She had mild dry eye before SCT. Oral and intestinal CGVHD developed, and the dry eye worsened significantly on approximately day 150 while tapering FK506. Treatment with prednisolone (1 mg/kg/d) began, and the dose of FK506 was increased. By day 240, the symptoms of dry eye and the findings of the ocular surface markedly improved, and CGVHD in other organs was completely resolved. However, the improvement in the dry eye was lost when FK506 was tapered for the second time. CONCLUSION: Systemic administration of FK506 with corticosteroids is an effective treatment of severe dry eye in patients with CGVHD, but long-term administration may be required to achieve a lasting response. These cases also suggest that further investigation into the use of topical FK506 and prednisolone as a maintenance therapy should be pursued.

Adult↗

PubMed2001

Interleukin-8 concentrations in conjunctival epithelium brush cytology samples correlate with neutrophil, eosinophil infiltration, and corneal damage.

PURPOSE: To evaluate whether interleukin-8 (IL-8) and RANTES (regulated on activation, normal T-cell expressed and secreted) concentrations in the supernatants of conjunctival epithelial samples from patients with vernal keratoconjunctivitis (VKC) correlate with the number of infiltrating eosinophils or neutrophils and with the severity of corneal lesions. METHODS: Thirty-four patients with VKC, 5 patients with seasonal allergic conjunctivitis, and 10 volunteers without allergic diseases were enrolled in this study. Conjunctival epithelial cells were collected by brush cytology and the number of inflammatory cells was counted. The chemokine expression in the cells was investigated by immunocytochemistry and the chemokine concentrations of the cell suspensions were measured by enzyme-linked immunosorbent assay. RESULTS: The percentages of eosinophils and neutrophils in cell suspensions from VKC patients with corneal erosion or ulcer were higher than those from subjects with clear corneas or superficial punctate keratopathy. IL-8 concentrations in the supernatant of samples correlated significantly with the percentages of neutrophils and eosinophils in paired cell suspensions. No correlation was observed between RANTES and the percentages of eosinophils. Positive staining for IL-8 was observed in the cytosol of conjunctival epithelial cells. CONCLUSION: IL-8 in the extracellular space of the conjunctival epithelium may play a role in the recruitment of neutrophils and possibly eosinophils and in the pathogenesis of corneal damage in severe allergic diseases.

Adolescent↗

PubMed2001

Treatment of superior limbic keratoconjunctivitis by application of autologous serum.

PURPOSE: To determine the efficacy of autologous serum drops in the treatment of superior limbic keratoconjunctivitis (SLK). METHODS: Twenty-two eyes of 11 patients were diagnosed with SLK. All eyes were treated with 20% diluted autologous serum eyedrops 10 times a day in addition to ongoing treatment of dry eye. Fluorescein and rose bengal staining scores, as well as subjective symptom gradings, were performed before and after 4 weeks of therapy. RESULTS: Nine of the 11 patients responded well to treatment (82%). The average rose bengal and fluorescein score improved ( p < 0.05), and there was subjective improvement. CONCLUSION: Autologous serum application can be used as an alternative mode of therapy in SLK.

Administration, Topical↗

PubMed2001

Dry eye after refractive surgery.

Photorefractive keratectomy and laser in situ keratomileusis can induce or exacerbate dry eye after surgery. This manifests as an increase in degree and frequency of symptoms, corneal findings, such as superficial punctate keratopathy, and abnormal results of dry eye tests, such as the Schirmer test and tear break-up time. The cause mainly involves decreased corneal sensation, resulting in decreased feedback to the lacrimal gland and reduced tear production. Other causes may include increased evaporation, inflammation, or toxicity of medications. Dry eye may result infrequently in impaired wound healing and decreased optical quality of the cornea, but it is transient, lasting from a few weeks up to 1 year. Patients should be warned about this distressing complication. During a period of dry eye, artificial tears and punctal plugs are helpful in preventing or alleviating patient discomfort.

Cornea↗

PubMed2001

Trabecular surface remodeling simulation for cancellous bone using microstructural voxel finite element models.

A computational simulation method for three-dimensional trabecular surface remodeling was proposed, using voxel finite element models of cancellous bone, and was applied to the experimental data. In the simulation, the trabecular microstructure was modeled based on digital images, and its morphological changes due to surface movement at the trabecular level were directly expressed by removing/adding the voxel elements from/to the trabecular surface. A remodeling simulation at the single trabecular level under uniaxial compressive loading demonstrated smooth morphological changes even though the trabeculae were modeled with discrete voxel elements. Moreover, the trabecular axis rotated toward the loading direction with increasing stiffness, simulating functional adaptation to the applied load. In the remodeling simulation at the trabecular structural level, a cancellous bone cube was modeled using a digital image obtained by microcomputed tomography (microCT), and was uniaxially compressed. As a result, the apparent stiffness against the applied load increased by remodeling, in which the trabeculae reoriented to the loading direction. In addition, changes in the structural indices of the trabecular architecture coincided qualitatively with previously published experimental observations. Through these studies, it was demonstrated that the newly proposed voxel simulation technique enables us to simulate the trabecular surface remodeling and to compare the results obtained using this technique with the in vivo experimental data in the investigation of the adaptive bone remodeling phenomenon.

Animals↗

PubMed2001

Lack of evidence for an increased microchimerism in the circulation of patients with Sjögren's syndrome.

OBJECTIVE: To examine the hypothesis that fetal microchimerism plays a part in the pathogenic process of Sjögren's syndrome (SS). METHODS: Genomic DNA samples were extracted from peripheral blood whole nucleated cells and the CD34+ cell enriched fraction of patients with SS and healthy women who had male offspring as well as nulliparous women. A Y chromosome-specific sequence was detected as a marker for fetal cells by a nested polymerase chain reaction (PCR) and by DNA hybridisation combined with PCR using specific primers and probes. All procedures were performed with great care to avoid the contamination of male DNA. RESULTS: A nested PCR and DNA hybridisation combined with PCR was established that can detect a single male cell out of 1.67x10(5) female cells. It was not possible to increase the sensitivity further because the amount of template DNA held in the PCR was limited. When these methods were used, no fetal cells were detected in any samples from patients with SS, though they were detected in whole nucleated cells from two healthy women who had delivered sons previously. CONCLUSIONS: The findings indicate that circulating fetal cells in patients with SS are uncommon (<1 in 1.67x10(5)), if they exist. With the conventional PCR based methods that were used, it is difficult to evaluate the quantitative difference in circulating fetal cells between patients with SS and healthy women.

Adult↗