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Biomedical subjects

H Iijima

Publications and source records attributed to H Iijima.

At least 73 records · Page 4Linked to original sources

Optical coherence tomography of cystoid macular edema associated with retinitis pigmentosa.

PURPOSE: To detect cystoid macular edema in consecutive eyes with retinitis pigmentosa by means of optical coherence tomography and to study the correlation between cross-sectional structures and angiographic findings in cystoid macular edema. METHODS: In a prospective study, cross-sectional images through the fovea were evaluated by means of optical coherence tomography in 89 phakic eyes of 46 patients with retinitis pigmentosa. Eyes showing cystoid appearance in the macula in the optical coherence tomographic images were further studied with measurement of the dimensions of cystoid lesions and with a fluorescein angiogram either at 18 minutes after dye injection or later. RESULTS: Cystoid lesions were observed in the macula in optical coherence tomographic images in 12 eyes in six (13%) of 46 patients. In these eyes, the width of total area of the cystoid lesions was positively correlated with the grade of fluorescein angiogram (Spearman rank correlation coefficient, r = .629; P = .029), but the thickness of the neurosensory retina at the center of the fovea was not. Among three variables for grading cystoid macular edema, consisting of angiographic grade, thickness of the neurosensory retina at the center of the fovea, and width of total area of the cystoid lesions, only the last measure was significantly correlated with best-corrected visual acuity (Pearson correlation coefficient, r = .693; P = .012). CONCLUSION: Cystoid macular edema in eyes with retinitis pigmentosa could easily be detected with the use of optical coherence tomography independent of the angiographic degree of dye leakage. The size of cystoid lesions demonstrated in the optical coherence tomographic images, especially the thickness of the neurosensory retina at the center of the fovea, was not necessarily correlated with the angiographic grading of dye leakage. Measurement of the width of total area of the cystoid lesions in the optical coherence tomographic images is significantly correlated with the loss of visual acuity.

Adolescent↗

Optical coherence tomography of successfully repaired idiopathic macular holes.

PURPOSE: To present the cross-sectional retinal imaging results of optical coherence tomography in eyes with successfully repaired idiopathic macular hole and their relevance to visual recovery. METHODS: We studied 33 eyes with successful repair of an idiopathic macular hole through vitrectomy and fluid-gas exchange from 32 patients (11 men and 21 women) with ages ranging from 48 to 78 years, with a median age of 66 years. Preoperative conditions in eyes with primary surgery disclosed nine eyes with stage 2, 14 eyes with stage 3, and four eyes with stage 4 macular hole. An additional six eyes underwent a second surgery because the previous surgery was unsuccessful. Measurement of best-corrected visual acuity, slit-lamp biomicroscopy with fundus contact lens, fundus photographs, and optical coherence tomographic examination were performed between 6 and 9 months after surgery in 29 eyes and between 15 and 36 months after surgery in four eyes. RESULTS: Optical coherence tomographic images of the repaired macular holes were categorized into three patterns. U-type (normal foveal contour; 13 eyes) showed mildly to moderately backscattering layers with a smooth circular surface covering retinal pigment epithelium and choriocapillaris layers. In eyes with V-type (steep foveal contour; 13 eyes), the retinal pigment epithelium and choriocapillaris layers were covered with moderately backscattering layers with a notch. W-type (foveal defect of neurosensory retina; seven eyes) showed abruptly or gradually terminating sensory retinal layers to expose the surface of the retinal pigment epithelium and choriocapillaris layers. Postoperative acuity was well correlated with these patterns of optical coherence tomographic images. CONCLUSION: Assessment of successfully repaired idiopathic macular holes with optical coherence tomographic images provides a useful correlation with postoperative visual recovery.

Aged↗

Time-dependent effects of stressor application on metastasis of tumor cells in the lung and its regulation by an immunomodulator in mice.

The effects of the timing of stressor application on transplanted tumor cells and its possible regulation by an immunomodulator was investigated. Male C57 BL/6N mice were subjected to rotational stressor for 7 days relative to tumor cell inoculation: stressor after inoculation of Lewis lung cancer cells, stressor during inoculation and stressor before inoculation. Stressor application and tumor cell inoculation induced transient decreases in body weight, particularly in mice stressed after inoculation. The mice exposed to the stressor during inoculation or before inoculation showed significant increases in the number of metastatic foci relative to control mice. Early administration of an immunomodulator, PSK, significantly attenuated the increase of metastatic foci in stressed mice. The weights of thymus gland and spleen at 14 days after inoculation were similar in the three stressor groups and the control group. Application of the stressor reduced NK cell activity of the normal mice as well as tumor bearing mice. The lowest pre-inoculation NK cell activity was observed in mice stressed for 7 days beginning on the day of inoculation. The NK cell activity decreased in the tumor bearing mice which were stressed at the time of tumor inoculation. Decreased NK cell activity was reversed at day 14 after tumor inoculation. The mice exposed to the stressor after inoculation showed lowest level of NK cell activity relative to mice exposed to the stressor before or during inoculation. The treatment of mice with PSK reduced these changes significantly. The present results suggest that the rotational stress reduces splenic NK cell activity, which may influence the magnitude of tumor metastasis, depending on the time of tumor cell injection. Further, administration of an immunomodulator may counteract the reduction of the NK cell activity.

Adjuvants, Immunologic↗

Assessment of potential macular function using a color saturation discrimination test in eyes with cataract.

PURPOSE: To study the efficacy of a color saturation discrimination test (CSDT) in assessing potential macular function in eyes with cataract. SETTING: Yamanashi Medical University and Nirasaki City Hospital, Yamanashi, Japan. METHODS: In this prospective study of 200 consecutive eyes with cataract, the thresholds of color saturation discrimination on 6 hues were measured with the CSDT. The CSDT program was run on a personal computer and cathode-ray tube color monitor. The preoperative CSDT scores and postoperative visual acuities were compared. In addition, preoperative laser interferometry (LI) and postoperative CSDT were performed on selected patients and the results compared with their preoperative CSDT results. RESULTS: Patients who had a CSDT score of 11 or more had a significantly lower postoperative visual acuity (P < .0001). The prevalence of neuroretinal abnormality postoperatively increased with the preoperative CSDT score. The CSDT score was not correlated with preoperative visual acuity (P = 1409). Cataract severity had little influence on the CSDT score. The preoperative results of the CSDT and Ll were correlated with the postoperative acuity, with the correlation coefficient being stronger with the CSDT (r = -0.338 and 0.276 for CSDT and Ll, respectively). CONCLUSION: The CSDT was effective in evaluating neuroretinal pathology and predicting postoperative acuity.

Cataract↗

Visual field change in eyes with retinal pigment epithelial tear.

PURPOSE: To study the effects of retinal pigment epithelial (RPE) deprivation on retinal sensitivity with serial automated static perimetry in cases of RPE tear involving the foveal area. METHODS: Two eyes with a tear of the RPE were diagnosed as such on biomicroscopic and fluorescein angiographic examination. Static perimetry was performed in the follow-up study with the Humphrey field analyzer central 10-2 program. RESULTS: The first patient showed a dense scotoma corresponding to a defect in the RPE, which showed mild deterioration throughout the follow-up period from 2-11 weeks after the development of RPE tear. In contrast, the second patient showed preserved visual acuity and an absence of central visual field defects, despite an apparently denuded Bruch membrane involving the fovea during 8-month follow-up. CONCLUSION: Apparent RPE defect in eyes with RPE tears may or may not be associated with severe visual field defects. The pathophysiology of the disease should be studied, considering these perimetric findings.

Aged↗

Suplatast tosilate inhibits late response and airway inflammation in sensitized guinea pigs.

The effect of suplatast tosilate, which has been proven to inhibit T-cell synthesis of IL-4 and IL-5, on the response to antigen inhalation challenge was investigated in sensitized guinea pigs. The animals were given an oral dose of 30 or 100 mg/kg of suplatast or vehicle (distilled water) daily for 1 wk before antigen challenge. Measurement of pulmonary resistance for 6 h was followed by bronchoalveolar lavage and lung fixation. After antigen challenge, all guinea pigs in the vehicle group displayed dual-phase airway obstruction and accumulation of eosinophils and lymphocytes in the airways. After 1 wk of treatment with the high dose of suplatast, the late asthmatic response and the recruitment of eosinophils and lymphocytes into the airways were significantly inhibited, but the early asthmatic response was not affected. In situ hybridization revealed that challenge-induced increases in IL-5 mRNA-positive cells in lung tissue were significantly inhibited after treatment. Thus, suplatast inhibited airway obstruction in the late phase by specifically inhibiting the inflammatory process after mast cell degranulation.

Airway Resistance↗

[Effects of an ATP-sensitive K+ channel activator, JTV-506, on antigen-induced early and late asthmatic responses in sensitized guinea pigs].

Effects of an ATP-sensitive K+ channel activator, JTV-506, on dual asthmatic responses and airway inflammation after antigen inhalation challenge were investigated in asthma model of guinea pigs. The animals were given an oral dose of 1 mg/kg of JTV-506 or vehicle (0.5% carboxymethyl cellulose sodium) 1 hour before and 3 hours after antigen inhalation challenge. Measurement of pulmonary resistance for 6 h was followed by bronchoalveolar lavage. After antigen challenge, all guinea pigs in the vehicle group displayed dual-phase airway obstruction and accumulation of eosinophils in the airways. After the treatment with JTV-506, the early asthmatic response was significantly inhibited, although the late asthmatic response or the recruitment of eosinophils into the airways were not inhibited. Therefore, we suggested that JTV-506 may inhibit airway smooth contraction induced by chemical mediators, but not function of CD4+ T lymphocytes.

Airway Resistance↗

Deletion of bone marrow stromal cell antigen-1 (CD157) gene impaired systemic thymus independent-2 antigen-induced IgG3 and mucosal TD antigen-elicited IgA responses.

Bone marrow stromal cell Ag-1 (BST-1; CD157)-deficient mice were generated to examine the immunologic roles of the molecule in vivo. In BST-1(-/-) mice, the development of peritoneal B-1 cells was delayed, and CD38(low/-) B-lineage cells were increased in the bone marrow and spleen. Partial impairment of thymus-independent (TI-2) and thymus-dependent (TD) Ag-specific immune responses was noted in the systemic and mucosal compartments of BST-1(-/-) mice, respectively. Although serum Ig levels as well as TD and TI-1 Ag-specific systemic immune responses were normal, the TI-2 Ag-induced IgG3 response was selectively impaired. Oral immunization of BST-1(-/-) mice with cholera toxin, a potent TD Ag for the induction of IgA response, resulted in the poor production of Ag-specific Abs at the intestinal mucosa accompanied by the reduced number of Ag-specific IgA-producing cells in the lamina propria. These results indicate that BST-1 has roles in B cell development and Ab production in vivo.

ADP-ribosyl Cyclase↗

Molecular cloning and characterization of Ca2+-dependent inducible nitric oxide synthase from guinea-pig lung.

We have isolated a full-length cDNA for an inducible nitric oxide synthase (iNOS) from guinea-pig lung. The cDNA has a 3447 bp open reading frame encoding 1149 amino acid residues. The deduced amino acid sequence is approx. 80% identical with iNOS of human epithelial cells and murine macrophages. Consensus recognition sites for cofactors are highly conserved. COS cell lysate transfected with the guinea-pig iNOS shows significant levels of nitric oxide synthase (NOS) activity, and this is inhibited by 79% by chelation of Ca2+ ions. The NOS activity is restored in a concentration-dependent manner by increasing the free Ca2+ level. The NOS activity is also inhibited by trifluoperazine, a calmodulin antagonist, which suggests that the Ca2+ dependence is due to Ca2+-dependent calmodulin binding to the enzyme. Northern blot analysis reveals that the cloned iNOS mRNA is expressed in the lung and the colon in normal guinea pigs. Stimulation in vivo by lipopolysaccharide induces the expression of iNOS in the kidney, the spleen and the colon, but in the lung the same stimulation decreases its expression. These results suggest that the cloned guinea-pig iNOS is distinct in characteristics and expression from previously described iNOS forms.

Amino Acid Sequence↗

Nasal immune system: distinctive Th0 and Th1/Th2 type environments in murine nasal-associated lymphoid tissues and nasal passage, respectively.

The nasal mucosa, an important arm of the mucosal immune system, is the first site of contact with inhaled antigens to induce an IgA response. A major aim of this study was to characterize the Th1 and Th2 cytokine expression of mucosal T cells residing in nasal-associated lymphoid tissue (NALT) and nasal passages (NP) as IgA inductive and effector sites, respectively, at the transcription and cellular levels. An application of single-cell reverse transcription-PCR for analysis of Th1 (IFN-gamma) and Th2 (IL-4 and IL-6) cytokine-specific mRNA revealed the presence of CD4+ T cells with a Th0 profile in NALT, while high numbers of Th2 cytokine-specific mRNA expressed by CD4+ T cells were noted in NP followed by Th1-type cells. NALT CD3+ CD4+ T cells of Th0 type have the capacity to become Th1- and/or Th2-type cells since their activation via the TCR-CD3 complex resulted in the expression of an array of Th1 and Th2 cytokines. CD3+ CD4+ T cells from NP, but not NALT, provide a helper function for the induction of antibody-forming cells including IgA isotype in B cell cultures. These findings suggest that NALT is characterized by a Th0 environment which can gain a Th1 and/or Th2 phenotype. In contrast, NP is considered to be a Th2 dominant site with some Th1 cells that can support the induction of IgA-producing cells.

Animals↗

Familial dysplasminogenemia with central retinal vein and cilioretinal artery occlusion.

PURPOSE: To report a 49-year-old woman with unilateral central retinal vein occlusion and ipsilateral cilioretinal artery occlusion who showed familial dysplasminogenemia associated with elevated lipoprotein(a). METHOD: Case report. RESULTS: Extensive hemostatic and coagulation studies for causes of thrombosis, as well as family studies, disclosed decreased plasminogen activity without reduction of plasminogen antigen in the patient, her two siblings, and her two children. The patient also showed elevated lipoprotein(a). CONCLUSION: The combination of decreased plasminogen activity and elevated lipoprotein(a) should be considered as a possible cause of retinal vein and artery occlusion.

Ciliary Arteries↗

Thrombin-antithrombin III complex in acute retinal vein occlusion.

PURPOSE: To determine whether quantitative differences in systemic hypercoagulable state could be identified among patients with retinal vein occlusion at various sites of occlusion. METHODS: The value of thrombin-antithrombin III complex was determined in 57 patients with retinal vein occlusion within 1 month after the subjective onset of retinal vein occlusion and in 15 age-matched normal controls. RESULTS: Levels of log thrombin-antithrombin III complex were significantly higher in the patients with proximal retinal vein occlusion in which the occlusion site is at the optic disc (mean +/- SD, 0.493 +/- 0.389) than in those with distal retinal vein occlusion in which the occlusion site is away from the optic disc (0.312 +/- 0.150, P = .025) and in the normal controls (0.294 +/- 0.151, P = .020). There was no significant difference between the distal retinal vein occlusion and the normal controls (P = .720). More patients with proximal retinal vein occlusion showed elevated thrombin-antithrombin III complex values more than 3.9 ng/ml than those with distal retinal vein occlusion (8/29 vs 1/28, P = .025). Of nine patients showing an initial value of thrombin-antithrombin III complex of more than 3.9 ng/ml, repeated measurements were obtained in eight patients, who showed reduced value of thrombin-antithrombin III complex in the normal range in several months. CONCLUSIONS: A systemic hypercoagulable state, which could be demonstrated with the elevation of thrombin-antithrombin III complex value, may contribute more to the development of retinal vein occlusion with thrombus at or near the trunk of the central retinal vein than those with thrombus at branch veins away from the optic disc in the retina.

Acute Disease↗

Orally administered cholera toxin prevents murine intestinal T cells from staphylococcal enterotoxin B-induced anergy.

BACKGROUND & AIMS: Cholera toxin (CT) has been shown to be a strong mucosal adjuvant for the induction of antigen-specific secretory immunoglobulin A (IgA). The mechanism of adjuvant activity of CT is still unknown. The aim of this study was to examine the immunomodulatory function of CT on mucosal T cells using staphylococcal enterotoxin B (SEB) as coadministered oral antigen, because SEB has been shown to directly regulate alpha beta T-cell responses. METHODS: C3H/HeN mice were orally or systemically immunized with SEB and/or CT. The levels of SEB-specific antibodies and frequencies of CD4(+)Vbeta8(+) T cells were analyzed. SEB-specific T-cell proliferation and cytokine production were also determined. RESULTS: Neither SEB-specific IgA nor IgG antibodies were induced in feces when SEB was administered alone. This was a result of the clonal deletion and partial unresponsiveness of CD4(+)Vbeta8(+)T cells in Peyer's patches. On the other hand, SEB-specific antibodies were induced by oral immunization with SEB and CT. Although some degree of clonal deletion was induced by oral immunization with SEB and CT, coadministered CT prevented the induction of anergy for CD4(+)Vbeta8(+) T cells in Peyer's patches. CONCLUSIONS: CT is a powerful immunomodulatory molecule that prevents mucosal T cells from SEB-induced anergy.

Administration, Oral↗

Structure-activity relationship and conformational analysis of monoglycosylceramides on the syngeneic mixed leukocyte reaction.

We examined effects of alpha-, beta-galactosylceramides (CalCers) and alpha-, beta-glucosylceramides (GlcCers) on the syngeneic mixed leukocyte reaction (MLR) using spleen cells (responder cells) and dendritic cells (DC, stimulator cells). The DC pretreated with these alpha-monoglycosylceramides markedly stimulated the proliferation of spleen cells, in contrast to the little stimulatory effects produced by the DC pretreated with the corresponding beta-anomers. In addition, when we compared the effects of alpha-GalCer derivatives on the syngeneic MLR, it appeared that the 2"- and 3-hydroxyl groups in alpha-GalCers play a critical role in their stimulation of the MLR response. Based on these results, we performed a computer-aided molecular modeling study, and found that the orientations of the 2"-, 4"- and 3-hydroxyl groups common to alpha-GalCer and alpha-GlcCer are not accessible to those of inactive monoglycosyleeramides such as beta-GalCer. These results suggest that there might be a receptor-like site for alpha-monoglycosylceramides on the cells which are involved in the MLR response.

Animals↗

Contribution of cytokines on the suppression of lung metastasis.

Weekly injection of a protein-bound polysaccharide PSK in mice with Lewis Lung Cancer (LLC) significantly decreased the number of lung metastatic foci concomitant with enhancement of cytostatic activity in the bronchoalveolar lavage (BAL) cells. These effects were more marked when the agent was given intratracheally, inducing a larger number of pulmonary macrophages, lymphocytes and neutrophils concomitant with increases in BAL tumor necrosis factor-alpha (TNF-alpha), mouse inflammatory protein-alpha (MIP-1alpha), mouse inflammatory protein-beta (MIP-1beta), interleukin-1alpha (IL-1alpha) and interleukin-6 (IL-6), but not interleukin-2 (IL-2) and interleukin-4 (IL-4). Pre-treatment with anti TNF-alpha antibody reduced these effects. The time course and production of PSK-induced cytokines were similar between the tumor-bearing mice and control mice. BAL neutrophils in mice with LLC showed a tendency toward acceleration of O2- production compared with circulating neutrophils. Pulmonary macrophage phagocytosis was also significantly higher in the LLC mice. These results suggest that enhancement of cytostasis appears to be induced by activation and/or improvement of function in inflammatory and immune cells through cytokines under immunomodulator treatment in lung metastasis, possibly via a TNF-alpha-dependent mechanism.

Adjuvants, Immunologic↗

Role of endogenous nitric oxide in allergen-induced airway responses in guinea-pigs.

1. Endogenous nitric oxide (NO) can be detected in exhaled air and accumulates in inflamed airways. However its physiological role has not been fully elucidated. In this study, we investigated a role for endogenous NO in allergen-induced airway responses. Sensitised guinea-pigs were treated with NG-nitro-L-arginine methyl ester L-NAME (2.0 mM) or aminoguanidine (AG) (2.0 mM) 30 min before the allergen challenge, and 3 and 4 h after the challenge. Alternatively, L-arginine (2.4 mM) treatment was performed 30 min before, and 2 and 3 h after the challenge. In all groups, ovalbumin (OVA) challenge (2 mg ml(-1) for 2 min) was performed, and airway responses, NO production, infiltration of inflammatory cells, plasma exudation and histological details were examined. 2. Allergen-challenged animals showed an immediate airway response (IAR) and a late airway response (LAR), which synchronised with an increase in exhaled NO. Treatment with L-NAME and AG did not affect IAR while they significantly blocked LAR (72% and 80% inhibition compared to vehicle) and production of NO (35% and 40% inhibition). On the other hand, treatment with L-arginine did not affect IAR but potentiated LAR (74% augmentation). 3. In bronchoalveolar lavage (BAL) fluid, allergen-induced increases in eosinophils were reduced by 48% for L-NAME treatment compared to vehicle, and increased by 56% for L-arginine treatment. 4. Treatment with L-NAME significantly decreased airway microvascular permeability to both Monastral blue (MB) and Evans blue (EB) dye (50.6% and 44% inhibition). 5. We conclude that allergen-induced LAR is closely associated with NO production, and that NO plays a critical role in inflammatory cell infiltration and plasma exudation in the allergic condition.

Allergens↗

A novel acyl-CoA synthetase, ACS5, expressed in intestinal epithelial cells and proliferating preadipocytes.

We report here the identification, characterization, and expression of a novel rat acyl-CoA synthetase (ACS) designated as ACS5. ACS5 consists of 683 amino acids and is approximately 60% identical to the previously characterized ACS1 and ACS2. ACS5 was overproduced in Escherichia coli cells and then purified to near homogeneity. The purified enzyme utilized a wide range of saturated fatty acids similar to those utilized by ACS1 and ACS2, but differed in its preference for C16-C18 unsaturated fatty acids. Northern blot analysis revealed that ACS5 mRNA is present most abundantly in the small intestine, and to a much lesser extent in the lung, liver, adrenal gland, adipose tissue, and kidney. In situ hybridization of rat ileum revealed abundant accumulation of ACS5 transcripts in foveolar epithelial cells. The hepatic level of ACS5 mRNA was significantly increased by refeeding a fat-free high sucrose diet and reduced by fasting or refeeding a high cholesterol diet, whereas that in the small intestine was not significantly altered by various dietary conditions. In contrast to the absence of ACS1 mRNA in undifferentiated 3T3-L1 preadipocytes, ACS5 mRNA was present in proliferating 3T3-L1 preadipocytes and its level remained unaltered during differentiation, suggesting that ACS5 may provide the acyl-CoA utilized for the synthesis of cellular lipids in proliferating preadipocytes.

Adipocytes↗