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Biomedical subjects

H Fujishima

Publications and source records attributed to H Fujishima.

At least 19 recordsLinked to original sources
PubMed2006

Alterations of the ocular surface epithelial mucins 1, 2, 4 and the tear functions in patients with atopic keratoconjunctivitis.

BACKGROUND: An increased understanding of the ocular surface alterations at the cellular level in the conjunctiva and the cornea, may help explain the pathogenesis and the subsequent clinical appearance of atopic ocular allergies, which may be potentially blinding. PURPOSE: To investigate MUC 1, 2 and 4 alterations, tear function and the ocular surface disorder in patients with atopic keratoconjunctivitis. METHODS: Twenty-eight eyes of 14 atopic keratoconjunctivitis patients as well as 22 eyes of 11 age-and sex-matched normal subjects were studied. The subjects underwent corneal sensitivity measurements, Schirmer's test, tear film break-up time (BUT), fluorescein and Rose Bengal staining of the ocular surface, conjunctival impression cytology and brush cytology. Impression cytology samples underwent periodic acid-Schiff and immunohistochemical staining with MUC 1, 2 and 4 antibodies. Brush cytology specimens underwent evaluation for inflammatory cell numbers and quantitative real-time-PCR for MUC 1, 2 and 4 mRNA expression. Patient eyes with fluorescein and Rose Bengal scores greater than four points were regarded to have significant epithelial disease in this study. RESULTS: The mean corneal sensitivity and BUT values were significantly lower in atopic patients with significant epithelial disease, compared with patients with insignificant epithelial disease and controls (P < 0.01). Brush cytology specimens from patients with significant epithelial disease revealed significantly higher numbers of inflammatory cells (P < 0.01). Specimens from patient eyes showed positive staining for MUC 1, 2 and 4. MUC 1, 2 and 4 mRNA expressions were significantly higher in eyes with significant epithelial disease compared with eyes with insignificant epithelial disease and eyes of control subjects. CONCLUSION: Ocular surface inflammation, decline in corneal sensitivity, tear film instability, changes in conjunctival epithelial MUC 1, 2 and 4 mRNA expressions were thought to be important in the pathogenesis of atopic ocular surface disease.

Adolescent↗
PubMed2004

Inflammatory cells in brush cytology samples correlate with the severity of corneal lesions in atopic keratoconjunctivitis.

BACKGROUND: Inflammatory cells infiltrating to the tarsal conjunctiva are thought to be involved in the pathogenesis of corneal lesions in severe allergic conjunctival diseases. The relation between such cells and the severity of corneal lesions was studied. METHODS: Six patients with atopic keratoconjunctivitis (AKC) were enrolled in this study. Tarsal brush cytology findings and the severity of corneal damage at that point were recorded and analysed for correlation. RESULTS: Four out of six patients exhibited correlation between eosinophils and corneal damage. Three out of six patients exhibited correlation between neutrophils and corneal damage. Two out of six patients exhibited correlation between both eosinophils and neutrophils and corneal damage. Analysis of all data from all patients taken together revealed that both eosinophils and neutrophils in brush cytology samples significantly correlated with corneal damage. CONCLUSIONS: Inflammatory cells in brush cytology samples correlated with corneal damage. Evaluation of the relative percentages of inflammatory cells in brush cytology samples is a useful method of assessing disease activity in allergic conjunctival disease.

Adolescent↗
PubMed2002

kdsA mutations affect FtsZ-ring formation in Escherichia coli K-12.

No one has, as yet, addressed the relationship between the nature of the outer membrane and cell division. kdsA encodes 3-deoxy-D-manno-octulosonic acid (KDO) 8-phosphate synthetase which catalyses the first step in the synthesis of KDO, the linker between lipid A and oligosaccharide of lipopolysaccharide (LPS). Seven temperature-sensitive mutants containing missense mutations in kdsA were affected in the production of KDO and all mutants stopped dividing at 41 degrees C and formed filaments with either one or no FtsZ ring. All observed defects were reversed by the plasmid-borne wild-type kdsA gene. Western blotting analysis, however, demonstrated that the amount of FtsZ protein was not affected by the mutation. The mutants were more susceptible to various hydrophobic materials, such as novobiocin, eosin Y and SDS at 36 degrees C. Methylene blue, however, restored kdsA mutant growth. Plasmid-borne wild-type msbA, encoding a lipid A transporter in the ABC family, partially suppressed kdsA mutation. A mutation of lpxA, functioning at the first stage in lipid A biosynthesis, inhibited both cell division and growth, producing short filaments. These results indicate that the instability of the outer membrane, caused by the defect in KDO biosynthesis, affects FtsZ-ring formation.

Aldehyde-Lyases↗
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

A novel approach to the taxane BC ring system through formation of alpha-ketol by oxidative removal of the phenylsulfonyl group with subsequent in situ oxidation.

Cis-fused bicyclo[6.4.0]dodecene 11 was converted into taxane BC ring system 21 in three steps; transformation of the phenylsulfonyl group to an alpha-hydroxy carbonyl group by the treatment with potassium hexamethyldisilazide (KHMDS) and triethyl phosphite under oxygen atmosphere, followed by reductive elimination of the hydroxyl group of alpha-ketol moiety, and inversion of ring juncture. Epimerization of the sulfonyl group of 11 was indispensable for the first oxidation process (17 --> 18) and the second oxidation of 12 leading to hydroxylation at the alpha-position of the carbonyl group proceeded with high regio- and stereoselectivity to give 13. On the other hand, reaction of the cross-conjugated compound 5 with KHMDS at 0 degrees C brought about a complete reorganization of molecular framework to provide the compound 7 in which the five-membered ring and the conjugated seven-membered ring were connected through a single bond.

Bridged-Ring Compounds↗
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

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

Antimalarial and cytotoxic activities of bicycl.

Biological evaluations of bicyclo[6.4.0]dodecenone derivatives on antimalarial activity in vitro against Plasmodium falciparum and cytotoxicity against human KB cells were made. (+/-)-(1R*,4S*,7R*,8S*)-4-tert-Butyl-dimethylsiloxy-5,5-dimethyl-1-methyl-9-methylene-7-phenylsulfonylbicyclo[6.4.0]dodec-2,11-dien-10-one (15) exhibited potent antimalarial activity, whereas (+/-)-(1R*,7R*,8S*)-1-methyl-9-methylene-7-phenylsulfonylbicyclo[6.4.0]dodec-2,11-dien-10-one (14) showed significant cytotoxic activity in human KB cells. Both 14 and 15 possess, as a structural character, the exo-methylene moiety in their 6-membered ring of the 8-6 fused ring system.

Animals↗
PubMed2000

Association of preoperative tear function with surgical outcome in severe Stevens-Johnson syndrome.

OBJECTIVE: To retrospectively study the surgical outcome in severe Stevens-Johnson syndrome (SJS). DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Twenty-nine eyes of patients with severe SJS associated with total conjunctivalization were examined. INTERVENTION: Preserved human amniotic membrane grafting and keratolimbal allograft transplantation was performed. Intensive immunosuppression and epithelial management were continued postoperatively. MAIN OUTCOME MEASURES: Successful ocular surface reconstruction was determined by epithelialization with corneal epithelium. The association between surgical outcome and preoperative tear function was studied. RESULTS: The ocular surface was successfully covered by corneal epithelium in 13 eyes (44.8%). The mean corrected visual acuity recovered from 0.0039 to 0.017. Persistent epithelial defect was the most common complication. Eyes with successful ocular surface reconstruction had significantly better preoperative Schirmer's test values (P = 0.025) and tear clearance rates (P = 0.043) than those that failed. CONCLUSIONS: In patients with severe SJS, preoperative tear function significantly influenced surgical outcome. Eyes with Schirmer's test value of >10 mm have a greater chance of successful ocular surface reconstruction.

Adolescent↗
PubMed2000

Trabeculectomy with mitomycin C for post-keratoplasty glaucoma.

AIM: To investigate the effect of trabeculectomy with and without mitomycin C in post-keratoplasty glaucoma. METHODS: A retrospective study was performed on patients who underwent trabeculectomy for glaucoma after penetrating keratoplasty. 34 eyes of 32 patients were included in this study. 26 eyes received trabeculectomy with mitomycin C and eight eyes without mitomycin C. The procedure was deemed successful if the intraocular pressure was maintained below 21 mm Hg with or without use of additional antiglaucoma medication (mean follow up time 22.3 (SD 10.3) months). RESULTS: At the last examination trabeculectomy was successful in 19 of 26 eyes (73.0%) with mitomycin C (+) and two of eight (25.0%) without (p=0.0219). When the prognosis was analysed by Kaplan-Meier curve, the mitomycin C (+) group showed a better prognosis (p=0.0182). Mean intraocular pressure and average number of glaucoma medications improved in the group with mitomycin C without severe side effects on the graft. Graft rejection after trabeculectomy was seen in two eyes in the mitomycin C group. Final graft clarity rate was 69.2% (18/26) in the mitomycin C (+) group and 37.5% (3/8) in the mitomycin C (-) group. Complications such as persistent epithelial defect, cystoid macular oedema, choroidal detachment, leakage from bleb were seen in four eyes in the mitomycin C (+) group and in one eye in the mitomycin C (-) group. CONCLUSIONS: Trabeculectomy with mitomycin C showed better results for glaucoma following keratoplasty.

Adult↗
PubMed1999

Cytosolic phospholipase A2 is essential for both the immediate and the delayed phases of eicosanoid generation in mouse bone marrow-derived mast cells.

We have used mice in which the gene for cytosolic phospholipase A2 (cPLA2) has been disrupted to demonstrate the absolute requirement for cPLA2 in both the immediate and the delayed phases of eicosanoid generation by bone marrow-derived mast cells. For the immediate phase, quantitative analysis of the products of the 5-lipoxygenase pathway showed that gene disruption of cPLA2 prevented the provision of arachidonic acid substrate for biosynthesis of proximal intermediates. By analogy, we conclude that arachidonic acid substrate was also not available to prostaglandin endoperoxide synthase 1 in the immediate phase of prostaglandin (PG) D2 generation. These defects occurred with two distinct stimuli, stem cell factor and IgE/antigen, which were, however, sufficient for signal transduction defined by exocytosis of beta-hexosaminidase. Whereas cPLA2 is essential for immediate eicosanoid generation by providing arachidonic acid, its role in delayed-phase PGD2 generation is more complex and involves the activation-dependent induction of prostaglandin endoperoxide synthase 2 and the supply of arachidonic acid for metabolism to PGD2.

Animals↗
PubMed1999

v-src induces cisplatin resistance by increasing the repair of cisplatin-DNA interstrand cross-links in human gallbladder adenocarcinoma cells.

Activation of Src, which has an intrinsic protein tyrosine kinase (PTK) activity, has been demonstrated in human solid tumors, such as colorectal and breast cancers. To investigate the role of activated Src in drug resistance, we evaluated the effect of v-src on the resistance to various anti-cancer drugs using v-src-transfected HAG-1 human gallbladder adenocarcinoma cells. Compared with parental or mock-transfected HAG-1 cells, v-src-transfected HAG/src3-1 cells showed a 3.5-fold resistance to cis-diamminedichloroplatinum (II) (CDDP) but not to doxorubicin, etoposide or 5-fluorouracil. By contrast, activated H-ras, which acts downstream of src, failed to induce resistance to either of these drugs. Furthermore, wortmannin, a phosphatidylinositol (PI) 3-kinase inhibitor, and H7, a protein kinase C (PKC) inhibitor, did not alter CDDP resistance. Evaluation of the kinetics of the removal of DNA interstrand cross-links (ICLs), measured by alkaline elution, showed a significant increase in this removal in HAG/src3-1 cells as compared with mock-transfected cells, though no differences were found in the formation of DNA ICLs between these cell lines. CDDP resistance in v-src-transfected cells was reversed, if not completely, by either herbimycin A or radicicol, specific inhibitors of Src-family PTKs, suggesting that Src tyrosine kinase activity induces CDDP resistance. Moreover, significant reduction in the repair of CDDP-induced DNA ICLs was observed upon treatment with radicicol. The intracellular glutathione content and mRNA expression of topoisomerase II and metallothionein were virtually identical between these cell lines, except for topoisomerase I mRNA. Our data strongly suggest that the ability of activated src, but not ras, to induce CDDP resistance is mediated by augmentation of DNA repair through Src to downstream signal-transduction pathways distinct from either the Ras, PI 3-kinase or PKC pathway.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

Pregnanes and pregnane glycosides from Hoya carnosa.

Eleven pregnanes were isolated from the hydrolysate of the CHCl3 extract fractionated from the caules of Hoya carnosa. Among these, six pregnanes, including 19-acetoxydigipurpurogenin II, were new, and their structures were elucidated. The structures of twenty new pregnane tetraosides and pentaosides, named hoyacarnosides A-T, besides three known ones from the CHCl3 extract, were determined.

Carbohydrate Sequence↗
PubMed1998

Interferon-alpha and -gamma inhibit the growth and neoplastic potential of v-src-transformed human epithelial cells by reducing Src tyrosine kinase activity.

To investigate whether interferons (IFNs) selectively suppress the growth of solid tumor cells with elevated protein tyrosine kinase (PTK) activity, we evaluated the effect of recombinant IFN-alpha2a and IFN-gamma on the proliferative and neoplastic potentials triggered by p60v-src using v-src-transformed HAG-1 human epithelial cells. When compared with control cells harboring the pSV2neo gene, the monolayer growth of v-src-transformed cell lines was inhibited by both recombinant IFNs, in a dose-dependent manner, whereas growth of ras-transfected cell lines was not affected. Moreover, IFNs markedly reduced the clonogenic growth of v-src-transformed cells in soft-agar rather than monolayer growth, suggesting the preferential activity of IFNs on anchorage-independent growth. Pretreatment of cells with Src or the Src-like PTK inhibitor herbimycin A or radicicol, alleviated dose-dependently the growth-inhibitory activity of IFN-alpha2a against v-src-transformed cells, suggesting that IFNs may share a common inhibitory pathway with Src PTK inhibitors. Accordingly, like herbimycin A, IFNs were found to reduce tyrosine phosphorylation of p60v-src and suppressed in vitro p60v-src kinase activity in v-src-transformed cells. Our data, together with the fact that IFNs inhibit the growth potential driven by Src but not by activated Ras, suggest that inhibition of signal transduction pathway through Src to downstream transduction events may be a primary mechanism of IFN-induced anti-prolifeative and anti-tumoral activity.

Adenocarcinoma↗
PubMed1998

Allergic conjunctivitis as a risk factor for regression and haze after photorefractive keratectomy.

PURPOSE: To analyze the relation between allergic conjunctivitis and the results of photorefractive keratectomy performed with an excimer laser in myopic eyes. METHODS: Fifty-seven myopic eyes in 57 Japanese patients were classified into three groups: a normal group (30 eyes of 30 patients), a treatment group composed of eyes with allergic conjunctivitis that were treated with fluorometholone and cromolyn sodium eyedrops from month 3 until the end of the 12- to 18-month follow-up period (16 eyes of 16 patients), and a no-treatment group composed of eyes with allergic conjunctivitis that received no allergic treatment until the end of the follow-up period (11 eyes of 11 patients). Preoperative and postoperative examinations included evaluation of corrected and uncorrected visual acuity and grading of corneal haze. RESULTS: In the no-treatment group, the mean corneal haze score +/- SD of 0.8 +/- 0.98 was significantly greater than the normal group score of 0.38 +/- 0.49 (P = .02). There was no significant difference in the haze score between the treated and normal groups. A refractive outcome of +/- 1 diopter was obtained in 30 (100%) of the 30 patients in the normal group, 15 (93.8%) of 16 patients in the treatment group, and four (36.4%) of the 11 patients in the no-treatment group. Visual acuity was 20/40 or better after photorefractive keratectomy in 30 patients (100%) in the normal group, 15 patients (93.8%) in the treatment group, and six patients (54.5%) in the no-treatment group. CONCLUSION: These findings suggest that untreated allergic conjunctivitis is a significant risk factor for haze and myopic regression after photorefractive keratectomy.

Adult↗
PubMed1998

Trabeculectomy with the use of amniotic membrane for uncontrollable glaucoma.

Although trabeculectomy is an established surgical technique for glaucoma, in some cases it does not achieve a good filtering effect despite the use of mitomycin-C (MMC). The authors have developed a new surgical technique for uncontrollable glaucoma that uses amniotic membrane to prevent postoperative adhesion of conjunctiva and sclera. They performed trabeculectomy with a limbal-based conjunctival flap using 0.4 mg/ml of MMC for 2 minutes. Amniotic membrane was then placed under the scleral flap and sutured using 10-0 nylon. Among 14 eyes of 13 patients who underwent this procedure, intraocular pressure was controlled to less than 20 mm Hg after surgery in 13 eyes, including 3 eyes that underwent a second surgery with the same technique and 2 eyes that underwent laser trabeculoplasty. The authors' results suggest that this technique is efficacious for the reduction of intraocular pressure in high-risk glaucoma patients.

Adult↗