The mechanism for low yield of blood culture in invasive aspergillosis; the clinical importance of antigen detection tests revisited.
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Antigens, Fungal↗
Biomedical subjects
T Fujihara
Publications and source records attributed to T Fujihara.
Self-assembly of a porphyrin array via the molecular recognition approach: synthesis and properties of a cyclic zinc(II) porphyrin trimer based on coordination and hydrogen bonding.
Self-assembly of [5-(pyrazol-4-yl)-10,20-bis(p-tolyl)-15- (2-ethoxycarbonylphenyl)porphyrinato]-zinc(II) (1), designed to have both a coordination site and a hydrogen bonding site, leads to a stable cyclic trimer array where coordination of the pyrazole nitrogen to the zinc(II) ion as well as hydrogen bonding between carbonyl oxygen and pyrazole NH holds each zinc(II) porphyrin. The recognition event for pyrazole has been confirmed preliminarily in the model studies using [5-(2-ethoxycarbonylphenyl)tris(p-tolyl)porphyrinato]-zinc(II) (3). The zinc(II) porphyrin 3 has large affinity for pyrazole due to the hydrogen bond between pyrazole and the 2-ethoxycarbonyl group in addition to the coordination bonding accompanied by the conformational change of the ethoxycarbonyl group in the coordination process. The (1)H NMR, IR, and UV-vis spectra of 1 and its ESI-MS and VPO measurements have revealed the cyclic trimer structure with an overall association constant of 6.0 x 10(13) M(-2) at 22 degrees C. The contribution of the hydrogen bond to the total free energy change in trimer formation is estimated to be 7.5 kcal/mol based on a reference trimer system without a hydrogen bonding site. The trimer geometry causes characteristic exitonic interaction between porphyrin units to yield a broad Soret band which is deconvoluted into four components by UV-vis and MCD spectral analyses. Electrochemical measurements have shown that only the first ring-oxidation process proceeds stepwise in the trimer.
Electrochemistry↗
Cultural and gender differences in anger and aggression: a comparison between Japanese, Dutch, and Spanish students.
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Adolescent↗
Improvement of corneal barrier function by the P2Y(2) agonist INS365 in a rat dry eye model.
PURPOSE: Because purinoceptor P2Y(2) receptor agonists elicit increases in net Cl, fluid transport, and glycoprotein release onto the ocular surface, they are candidates for treatment of dry eye syndrome. Accordingly, the effects of such an agonist INS365 on these parameters were characterized in a rat dry eye model. METHODS: An SD rat dry eye model was used in which exorbital lacrimal gland extirpation decreased the Schirmer test score by at least 50%. After 8 weeks, when significant increases occurred in corneal epithelial permeability, INS365-containing eye drops were applied six times daily for the next 4 weeks at concentrations from 0.03% to 3.0%. Corneal barrier function was evaluated based on measurements with a modified anterior fluorometer of fluorescein penetrance at 1, 2, and 4 weeks after initial application. After INS365 application, the periodic acid-Schiff reagent (PAS)-stained area was evaluated in histologic sections of the tarsal and bulbar conjunctiva. RESULTS: Ten minutes after INS365 eye drop application at doses of either 3. 0% or 8.5%, a 1.5-fold transient increase in tear fluid secretion occurred in both the control and dry eye model animals. These transient increases nearly returned to baseline after 60 minutes. Furthermore, after 5 minutes, 1.0% INS365 was sufficient to cause a maximal transient decrease in the PAS-stained area of more than 30%, which thereafter recovered toward the initial level. Beginning at 2 weeks and continuing for an additional 2 weeks, maximal declines in dye penetrance of approximately 50% occurred with doses of INS365 as low as 1%. Such improvement in corneal epithelial resistance was accompanied by complete restoration of the PAS-stained area to the level seen in the control animal. CONCLUSIONS: In a rat dry eye model, the P2Y(2) agonist INS365 was found to improve surface health, based on increases in tear fluid secretion, corneal epithelial resistance, and release of glycoprotein-containing moieties from goblet cells. These effects suggest that INS365 is a potential therapeutic agent for use in the treatment of dry eye syndrome.
Animals↗
P2Y(2) receptor stimulation increases tear fluid secretion in rabbits.
PURPOSE: The purinergic P2Y(2) receptor agonists stimulate active Cl-transport across the excised rabbit conjunctival tissue in vitro. We determined whether UTP or ATP could increase the tear volume and change tear fluid composition in normal rabbits in vivo. METHODS: Fifty mL was applied to rabbit eyes of UTP, ATP at concentrations of 0.1, 0.3, 1, 3, 8.5% (1.8-154 mM) or saline. A modified Schirmer test with topical anesthesia was performed 5, 15, 30 and 60 min after the instillation. In studies lasting 30 days, 50 microL of 0.5% UTP was applied 6 times a day for 4 weeks. Tear samples were collected from the conjunctival sac with a glass microcapillary. The protein profile of the tear fluid was analyzed by SDS-polyacrylamide gel electrophoresis and total protein was measured with the Bradford assay. The Easy-Titer rabbit IgG assay kit was used for the determination of immunoglobulin G (IgG). RESULTS: UTP had dose-dependent stimulatory effects on tear secretion. It maximally increased tear secretion about 4-fold 15 min after its application. Similar effects were obtained with ATP. Repeated treatment with UTP reproducibly increased tear volume. Furthermore, UTP did not decrease total protein and IgG concentration in tear fluid and it had no effect on the protein profile. CONCLUSION: These data indicate that activation of P2Y(2) receptor increases tear fluid secretion accompanied with some proteins in normal rabbits. The purinergic agonists, UTP and ATP, have potential therapeutic value in the treatment of dry eye.
Adenosine Triphosphate↗
Lactoferrin protects against UV-B irradiation-induced corneal epithelial damage in rats.
PURPOSE: Lactoferrin supplementation suppresses ultraviolet light B (UV-B)-induced oxidation of cultures of human corneal epithelial cells. To investigate the protective effect of lactoferrin containing eyedrops against UV-B-induced corneal damage in vivo, we examined lactoferrin efficacy in a rat UV-B keratitis model. METHODS: Sprague-Dawley rats were irradiated with >10 kJ/m2 after anesthetization, and then corneal epithelial defect was observed at 24 h postirradiation. The pre- or postapplication of vehicle or lactoferrin-containing eyedrops was performed, and then corneal epithelial damage was scored based on fluorescein staining. RESULTS: Posttreatment with lactoferrin did not inhibit the extent of corneal damage and did not affect wound healing. However, pretreatment by topical application of lactoferrin suppressed development of a corneal epithelial defect induced by UV-B irradiation in rats. CONCLUSION: These results suggest that the presence of lactoferrin in human tear fluid may inhibit UV-induced corneal epithelial damage.
Animals↗
Increased expression of alpha2beta1-integrin in the peritoneal dissemination of human gastric carcinoma.
The prognosis of advanced gastric cancer remains poor, given the frequent incidence of peritoneal metastasis. beta1-integrin is known to be associated with metastasis, though few reports have addressed the expression of beta1-integrin subunits in gastric cancer at primary and peritoneal lesions from the perspective of individual cases. We studied specimens from primary tumors from 50 patients and from metastatic peritoneal lesions from 27 patients with gastric carcinoma, including specimens from 22 metastatic lesions taken from the same patients whose primary tumors were sampled. Expression of beta1-integrin subunits, alpha2-alpha6beta1 integrins, was studied using an immunohistochemical method. alpha2beta1-integrin was significantly expressed on a larger proportion of tumor cells in peritoneal metastasis (70.4%) than in primary tumors (48%) (p<0.05), though alpha3beta1, alpha4beta1, alpha5beta1 and alpha6beta1-integrins did not demonstrate significant discrepancy. The expression of alpha2beta1-integrin in peritoneal lesions was significantly increased compared with its expression in the primary lesion in the same individual. In contrast, no relationship was found between the expression level of beta1 integrins and clinicopathological parameters. Peritoneal implantation of gastric carcinoma might be closely associated with alpha2beta1-integrin.
Adult↗
[Improvement in the regimen for combined CDDP and CPT-11 chemotherapy].
UNLABELLED: Combination therapy with cisplatin (CDDP) and irinotecan hydrochloride (CPT-11) is expected to be effective against refractory tumors. The antitumor effect of CPT-11 is believed to depend on the area under the concentration-time curve (AUC) of SN 38, which is a metabolite of the prodrug CPT-11. Of the major adverse effects of CPT-11, leukopenia is dependent on the AUC of CPT-11 and severe diarrhea is believed to be dependent on the peak concentration (Cmax) of SN 38. Considering these properties of CPT-11, we investigated the administration of a new regimen. METHOD: The subjects were patients with gynecological cancer who consented to intra-arterial [IA] infusion. The patients received CDDP (30 mg/m2 over 2 hours) concurrently with CPT-11 (40 mg/m2 over 24 hours) at 2-week intervals. Plasma concentrations of platinum and CPT-11 were measured before and after administration. To prevent binding of SN 38 to the large intestinal mucosa, we performed 1) alkalization, 2) detoxification of SN 38, and 3) clearance of the large intestine. RESULT: 1) A decrease in tumor diameter or negative conversion on cytology and reduced tumor marker levels were observed in patients receiving IA infusion. 2) No serious adverse reactions occurred, except grade 3 diarrhea in one patient given infusion at the initial dose. 3) The rate of conversion from CPT-11 to SN 38 was about 10%, which was higher than the 3% rate after standard 90-minute intra-venous [i.v.] infusion. 4) In the patients treated with IA infusion, CPT-11 levels in venous blood were one thirty-third of those in arterial blood. 5) Regarding the venous blood concentration of platinum when CDDP (30 mg/m2) was administered, the AUC of free platinum in patients given IA infusion was about 2.5 times that after i.v. infusion. CONCLUSION: The IA infusion treatment produced a good clinical response with good compliance.
Adenocarcinoma↗
Preferential localization of CD8+ alpha E beta 7+ T cells around acinar epithelial cells with apoptosis in patients with Sjögren's syndrome.
The T lymphocytes that infiltrate the exocrine glands in Sjögren's syndrome (SS) play a key role in damaging glandular epithelial cells, but the mechanisms of this damage by T lymphocytes are not fully understood. To determine the cellular basis of this phenomenon, we focused our attention on the T lymphocytes around acinar epithelial cells in SS. We showed that CD8+ but not CD4+ T lymphocytes were located around the acinar epithelial cells and that a majority of these CD8+ T lymphocytes possess an unique integrin, alpha E beta 7 (CD103). The acinar epithelial cell adherent with alpha E beta 7 (CD103)+ CD8+ T lymphocytes was apoptotic. Both the perforin/granzyme B and Fas/Fas ligand pathways were implicated in the process of programmed cell death in lacrimal glands. These results suggested that alpha E beta 7 integrin, by interacting with E-cadherin, mediates the adhesion between CD8+ T lymphocytes and acinar epithelial cells in SS and participates in inducing epithelial cell apoptosis, leading to secretory dysfunction of exocrine glands, a hallmark of SS.
Adult↗
Cyclosporin A increases tear fluid secretion via release of sensory neurotransmitters and muscarinic pathway in mice.
Cyclosporin A, an immunosuppressant, has the potential to increase tear fluid secretion through mechanisms which are not yet well understood. To gain insight into this question, we investigated the effect of cyclosporin A containing eyedrops on lacrimation in normal mice. Topical application of 0.1% cyclosporin A eyedrops for 3 days significantly increased lacrimation. This response was completely blocked by pre-exposure to 1% capsaicin. Immunohistochemical analysis revealed that capsaicin treatment depleted substance P from the lacrimal gland. Furthermore, following 1% atropine treatment, which completely blocks pilocarpine-stimulated (500 micrograms kg-1, i.p.) lacrimation, application of 0.1% cyclosporin A eyedrops significantly increased lacrimation. However, this increase was less than the response seen with 0.1% cyclosporin A in the absence of atropine. Interestingly, substance P-induced tear secretion was also partially inhibited in atropine treated mice. These results suggest that cyclosporin A accelerates tear secretion by releasing neurotransmitters from sensory nerve endings which interacts with the parasympathetic nerves.
Administration, Topical↗
Involvement of dopamine D1-like receptors in mediating increases in protein secretion from rabbit lacrimal gland.
To identify and localize the dopamine receptor subtypes in rabbit lacrimal gland which mediate protein secretion, the effects were determined of different dopamine receptor subtype agonists, antagonists, and a beta adrenergic antagonist on this process. Protein secretion into the medium was quantified with the Bradford assay. Dopamine increased protein secretion between 10(-7) and 10(-4)M, and it could be maintained for a subsequent 80 min. The relatively selective D1-like receptor agonist, SKF-38393 (10(-4)M) had a similar effect which was suppressed by the D1-like receptor antagonist, SCH-23390. However, neither the D2-like receptor agonist, quinpirole (10(-4)M), nor the selective D2-like receptor antagonist, sulpiride (10(-4)M) altered either the basal level or the stimulated response to dopamine. The dopamine (10(-4)M)-elicited increases in protein secretion were completely suppressed in the presence of either 10(-4)M propranolol or 10(-4)M bretylium. Protein secretion in rabbit lacrimal gland is mediated by dopaminergic nerves through stimulation of the presynaptic D1-like receptor.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
Diseases associated with ocular surface abnormalities: the importance of reflex tearing.
AIM: To investigate the correlation between tear function tests and ocular surface integrity in patients with dry eye. METHODS: 297 dry eye patients (55 Sjögren's syndrome, two male and 53 female, average age 52.4 (SD 15.0) years, and 242 non-Sjögren's syndrome, 41 male and 201 female, average age 53.5 (14.1) years) were examined. The following tear function tests were performed: (1) cotton thread test, (2) Schirmer test with topical anaesthesia, (3) Schirmer test without anaesthesia, (4) Schirmer test with nasal stimulation, (5) tear clearance test, and (6) tear break up time (BUT). The ocular surface was evaluated by rose bengal and fluorescein staining. Correlation analysis was performed between each tear function index and vital staining scores. RESULTS: Among the six tear function tests, the Schirmer test with nasal stimulation correlated most with both of the vital stains (rho = 0.530 for rose bengal and 0.393 for fluorescein). The Schirmer test with or without anaesthesia correlated slightly with rose bengal staining, whereas tear clearance test and tear break up time slightly correlated with fluorescein staining. CONCLUSION: Vital staining of the ocular surface correlates most with reflex tearing measured by the Schirmer test with nasal stimulation.
Dry Eye Syndromes↗
Conjunctival epithelium expression of HLA-DR in dry eye patients.
PURPOSE: To compare conjunctival epithelium expression of HLA-DR and ICAM-1 with tear dynamics and ocular surface parameters. METHODS: Brush cytology and flow cytometry were used to quantitatively analyze HLA-DR and ICAM-1 expression in 28 dry eye patients. RESULTS: HLA-DR was expressed in 66% of the conjunctival cells of dry eye patients. This expression correlates with that of ICAM-1, as well as with the Schirmer test results (p < 0.05). CONCLUSION: This study confirmed that dry eye consists not only of ocular surface desiccation, but also of upregulation of the HLA-DR and ICAM-1 molecule in the conjunctival epithelium, possibly resulting in increased inflammation.
Antibodies, Monoclonal↗
Regulation of human leukocyte antigen expression in human conjunctival epithelium.
PURPOSE: To demonstrate that interferon-gamma (IFN-gamma) is the key cytokine responsible for the upregulation of HLA-DR antigen in conjunctival epithelial cells of Sjogren syndrome (SS) patients. METHODS: Flow cytometry of conjunctival epithelial cells from SS and non-SS dry eye patients was performed for the quantification of HLA-DR surface expression. With a conjunctival epithelial cell line (ChWK), HLA-DR regulation by various cytokines was evaluated, and confocal immunocytochemical and western blot analyses were performed to evaluate the activation of nuclear factorkappa B (NF-kappaB) and signal transducers and activators of transcription 1 and 3 (STAT1 and STAT3, respectively). RESULTS: HLA-DR expression was upregulated in conjunctival epithelial cells of SS patients but not in non-SS dry eye patient or healthy control subject. IFN-gamma was the only cytokine that effectively upregulated HLA-DR expression in ChWK, which was synergistically enhanced by tumor necrosis factor-alpha (TNF-alpha). IFN-gamma induced the nuclear translocation of NF-kappaB, but did not activate STAT1 or STAT3 in ChWK. CONCLUSIONS: Upregulation of HLA-DR antigen in the conjunctival epithelium of SS patients may be regulated by IFN-gamma through the activation of NF-kappaB.
Adult↗
Up-regulation of alphaEbeta7, a novel integrin adhesion molecule, on T cells from systemic lupus erythematosus patients with specific epithelial involvement.
OBJECTIVE: To determine the possible role of a novel integrin, alphaEbeta7, in the pathogenesis of systemic lupus erythematosus (SLE). METHODS: Expression of alphaEbeta7 was examined on peripheral blood lymphocytes (PBL) from normal subjects (n = 25) and patients with SLE (n = 31), primary Sjogren's syndrome (n = 7), or polymyositis/dermatomyositis (n = 8) by cytofluorometry and/or immunoprecipitation. Adhesion of alphaEbeta7+ T cells to HSG epithelial cells was investigated using a confocal image analyzer. RESULTS: After phytohemagglutinin stimulation, expression of alphaEbeta7 on PBL, especially on CD8+ T cells, was significantly higher in SLE patients than in normal subjects (P<0.01). Elevated alphaEbeta7 expression was associated with the presence of oral ulcers or serositis (P<0.05). Activated SLE T cells with enhanced alphaEbeta7 expression strongly adhered to HSG; this adhesion was partially blocked by anti-alphaEbeta7. CONCLUSION: Expression and adhesion of alphaEbeta7 on activated PBL was significantly increased in patients with SLE with epithelial involvement. This suggests a role of this novel integrin in tissue-specific retention of activated PBL, due to increased alphaEbeta7-E-cadherin interaction, which may contribute to epithelial inflammation.
Adult↗
Lacrimation and salivation are not related to lymphocytic infiltration in lacrimal and salivary glands in MRL lpr/lpr mice.
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Animals↗
Serum soluble Fas/APO-1 is increased in patients with primary Sjögren's syndrome.
The aim of the study was to elucidate the involvement of Fas antigen in human autoimmune disease, by analysing serum levels of soluble Fas/APO-1 protein in patients with various autoimmune diseases, including system lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), Behçet's syndrome and Sjögren's syndrome (SjS). The levels of soluble Fas/APO-1 in sera were quantitated by a sandwich enzyme-linked immunosorbent assay. Soluble Fas/APO-1 levels were significantly increased in serum from patients with primary Sjögren's syndrome (primary SjS) compared with control subjects. However, no significant differences in soluble Fas/APO-1 levels were noted in patients with secondary Sjögren's syndrome (secondary SjS) nor in patients with any of the other autoimmune diseases. The soluble Fas/APO-1 level in primary SjS patients with extraglandular diseases was significantly higher than that in patients without extraglandular diseases. These results suggest that soluble Fas/APO-1 protein may play an important role in the pathogenesis of primary SS.
Adult↗
Establishment of lymph node metastatic model for human gastric cancer in nude mice and analysis of factors associated with metastasis.
The actual mechanisms responsible for lymph node metastasis in gastric cancer are still unclear. To investigate the mechanisms of lymph node metastasis in gastric cancer, we established a lymph node metastatic model for human scirrhous gastric carcinoma. Lymph node metastasis had frequently developed after orthotopic implantation of OCUM-2M LN derived from a scirrhous gastric cancer cell line, OCUM-2M, which had low capacity for lymph node metastasis. We elucidated the different characteristics including binding ability, migratory capacity and immunoresponses induced by the cell surface molecules of these two cell lines. The binding ability to Matrigel and migratory capacity of OCUM-2M LN cells were significantly greater than those of OCUM-2M cells. On flow cytometric analysis, both OCUM-2M and OCUM-2M LN cells strongly expressed HLA-I (99.5 and 97.1%) and LFA-3 (76.6 and 99.2%) in level of expression between the two cell lines, but neither cell line expressed HLA-II (0.0 and 0.0%), B7-1 (0.0 and 0.0%) or B7-2 (0.4 and 0.3%). ICAM-1 expression in OCUM-2M LN cells was weaker (0.7%) than that in OCUM-2M cells (36.8%). Strong adhesiveness and cytotoxicity of mononuclear lymphocytes for OCUM-2M cells were observed in adhesion and cytotoxic assays, both of which were significantly decreased by the addition of anti-ICAM-1 antibodies. On the other hand, the adhesiveness and cytotoxicity of OCUM-2M LN cells were significantly less than those of OCUM-2M cells, and were not affected by the addition of anti-ICAM-1 antibodies. These findings suggest that decreased ICAM-1 expression in a new gastric cancer cell line with a high rate of lymph node metastasis may in turn decrease immune responses mediated through LFA-1-dependent effector cell adhesion, and that this escape from the immunosurveillance system may be one of the factors inducing lymph node metastasis. In conclusion, we established a gastric cancer cell line, OCUM-2M LN, with a high rate of lymph node metastasis. An in vivo lymph node-metastatic model with this cell line should be useful for analysing the mechanism and therapeutic approach of lymph node metastasis.
Adenocarcinoma, Scirrhous↗