A case of sterile corneal perforation after bone marrow transplantation.
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Acute Disease↗
Biomedical subjects
S Amano
Publications and source records attributed to S Amano.
Advanced glycation end product deposits in climatic droplet keratopathy.
BACKGROUND: Climatic droplet keratopathy (CDK), known as spheroid degeneration of the cornea, is one of the most frequent degenerative corneal disorders affecting visual function. However, the histochemical nature of the deposits seen in CDK is still unclear. AIM: To investigate the pathogenesis of CDK, we investigated the immunohistochemical localisation of advanced glycation end products (AGEs) in surgical specimens of CDK. METHODS: Immunohistochemical localisation of N(epsilon)-(carboxymethyl)-l-lysine (CML), N(epsilon)-(carboxyethyl)-l-lysine (CEL), pyrraline, pentosidine and imidazolone was examined in three corneas with CDK, six corneas with bullous keratopathy and three corneas without any corneal diseases. RESULTS: In all the specimens with CDK, immunoreactivity was strong in CML, moderate in pyrraline and pentosidine, and weak in imidazolone. Immunoreactivity was absent in CEL. In contrast, no immunoreactivity to CML, pyrraline, pentosidine, imidazolone or CEL was detected in corneas with bullous keratopathy, or in corneas without any corneal diseases. CONCLUSIONS: CDK is caused by an aggregation of AGE-modified proteins. The result is consistent with etiological findings that ultraviolet irradiation and ageing, both of which are accelerators of AGE formation, are closely related to the development of CDK.
Antibodies, Monoclonal↗
Blinking and superficial punctate keratopathy in patients with diabetes mellitus.
AIM: To evaluate blinking patterns in patients with diabetes mellitus and whether blinking contributes to the formation of superficial punctate keratopathy in diabetic patients. METHODS: We examined 163 patients with type II diabetes mellitus and 76 without diabetes. Blinks were recorded, analysed using six parameters, and compared between patients with and without diabetes. Multivariate regression analysis was performed to assess the influence of other ocular factors, such as status of tear lipid layer, tear breakup time, corneal sensitivity, the result of cotton thread test, or blinking rate related to superficial punctate keratopathy. RESULTS: In patients with diabetes, the average mean and maximum interblinking times were longer, the average coefficient of variation of interblinking time was higher, and the average blinking rates were lower than those in patients without diabetes. Multivariate regression analysis revealed that the status of tear lipid layer and tear breakup time were significantly relevant to superficial punctate keratopathy (P < 0.01). CONCLUSION: Interblinking time was longer in diabetic patients, resulting in a decreased blinking rate. The prevalence of superficial punctate keratopathy cannot be predicted from blinking patterns in patients with diabetes.
Aged↗
Allergens in Japanese patients with allergic conjunctivitis in autumn.
PURPOSE: The purpose of the current study is to evaluate the relation between various specific class E immunoglobulins (IgE) in the serum and allergic conjunctivitis in autumn. METHODS: Total IgE and specific IgE to 12 inhalant allergens were measured using the CAP system in 32 patients with allergic conjunctivitis in spring (spring group), 27 patients with allergic conjunctivitis in autumn (autumn group), and 40 healthy volunteers (control group). RESULTS: Specific IgE levels caused by house dust, Dermatophagoides pteronyssinus, and orchard grass were higher in the autumn group than in the spring group. The highest positivity rate for a specific allergen was 51.9% for house dust, followed by D. pteronyssinus(48.1%) in the autumn group, while the highest rate was 68.8 % for cedar pollen, followed by cypress pollen (59.4%) in the spring group. Correlation analysis showed that house dust was significantly correlated with animal epithelia, D. pteronyssinus, acarus, and Alternaria tenuis in the autumn group (P<0.001). CONCLUSIONS: These results suggest that house dust is the main cause of allergic conjunctivitis during autumn. In spring, cypress pollen is the largest cause of allergic conjunctivitis, while indoor allergens such as house dust, animal epithelia, D. pteronyssinus, and acarus are not causative allergens in Japan.
Adolescent↗
Fibulin-5 deposition in human skin: decrease with ageing and ultraviolet B exposure and increase in solar elastosis.
BACKGROUND: Fibulin-5 was recently found as a secreted extracellular matrix protein that functions as a scaffold for elastic fibres. However, the distribution of fibulin-5 in human skin and its changes during the ageing process are not known. OBJECTIVES: To explore the involvement of fibulin-5 in skin ageing, the age-dependent changes in fibulin-5 localization in human skin were examined compared with those of other elastic fibre components including elastin, fibrillin-1 and fibulin-2. Methods The distribution of elastin, fibrillin-1, fibrillin-2, fibulin-2 and fibulin-5 was investigated by means of immunohistochemistry using their specific antibodies. Skin samples were recovered from 12 healthy subjects undergoing plastic surgery. Ultraviolet (UV) B-irradiated or control nonirradiated buttock skin samples were obtained from two healthy volunteers at 2 days after the irradiation at 2 minimal erythemal doses. RESULTS: In the reticular dermis of young sun-protected skin from the upper arm, fibulin-5 colocalized with the other elastic fibre components, while in the papillary dermis fibulin-5 showed candelabra-like structures perpendicular to the epidermis with an unstained area just beneath the epidermis, which was similar to that of elastin but not fibrillin-1. Fibulin-5 in the reticular dermis decreased and disappeared with age even in sun-protected skin from the thigh, abdomen and upper arm. In sun-exposed skin, fibulin-5 was extremely reduced in the dermis of cheek skin even from a 20-year-old man. UVB irradiation reduced fibulin-5, fibulin-2 and elastin markedly, moderately and weakly, respectively, compared with levels in control nontreated skin. Interestingly, the deposition of fibulin-5 was increased in solar elastosis, like that of other elastic fibre components. CONCLUSIONS: These results suggest that fibulin-5 is a good marker of skin ageing and that the earlier loss of fibulin-5 may involve age-dependent changes in other elastic fibre components.
Adolescent↗
Protective effect of matrix metalloproteinase inhibitors against epidermal basement membrane damage: skin equivalents partially mimic photoageing process.
BACKGROUND: The epidermal basement membrane (BM) plays important roles in adhesion between epidermis and dermis, and in controlling epidermal differentiation. The BM has been reported to be damaged in sun-exposed skin. Although matrix metalloproteinases (MMPs) are believed to be involved in the BM damage, there is no good in vitro model for examining BM damage by MMPs or for exploring methods to protect the BM. OBJECTIVES: To examine the involvement of MMPs in BM damage and approaches to protect the BM from such damage by using an in vitro skin-equivalent (SE) model. METHOD: SE was prepared by culturing human keratinocytes on contracted collagen gel including human fibroblasts. MMP-1, -2, -3 and -9, laminin 5 and type IV and VII collagens were determined by specific sandwich ELISAs, and MMP-2 and MMP-9 were analysed by gelatin zymography. Histological examination of SE was also carried out. RESULTS: Despite production of BM components such as laminin 5 and type IV and VII collagens in SEs, BM was rarely observed at the dermal-epidermal junction. Several MMPs, such as MMP-1, -2, -3 and -9, were observed to be present in conditioned media and some of them were in active forms. Tissue inhibitor of metalloproteinase (TIMP)-2 was not detected, although TIMP-1 was present. Synthetic MMP inhibitors, CGS27023A and MMP-inhibitor I, which inhibit MMP-1, -2, -3 and -9, markedly augmented deposition of laminin 5 and type IV and VII collagens at the dermal-epidermal junction, resulting in the formation of continuous epidermal BM. CONCLUSIONS: Our results indicate that MMPs are involved in the degradation of BM in SEs, and that MMP inhibitors exert a protective effect against BM damage.
Basement Membrane↗
A randomised, placebo controlled clinical trial of the aldose reductase inhibitor CT-112 as management of corneal epithelial disorders in diabetic patients.
AIM: To evaluate the efficacy of topical aldose reductase inhibitor CT-112 (5-[3-ethoxy-4-pentyloxyphenyl]-2,4-thiazolidinedione) on corneal epithelial barrier function in diabetic patients. METHODS: This was a prospective, randomised, double masked placebo controlled study. 34 eyes of 34 diabetic patients were randomly assigned treatment with 0.25% eye drops of CT-112 (n = 22) or a placebo (n = 12) four times a day for 8 weeks. Corneal fluorescein staining and corneal sensation were examined before treatment as well as 4 and 8 weeks after administration. Corneal epithelial permeability to fluorescence was measured with an anterior fluorophotometer. RESULTS: Average scores of superficial punctate keratopathy and corneal sensitivity did not differ significantly between the two groups at any time. Whereas average fluorescein concentrations did not differ significantly for the CT-112 and placebo groups before treatment, they did differ significantly 4 and 8 weeks after treatment (4 weeks, p = 0.0327; 8 weeks, p = 0.0143). CONCLUSION: The topical aldose reductase inhibitor, CT-112 improves the corneal epithelial barrier function in diabetic patients.
Aged↗
Association of clinical features with HLA in chronic pulmonary thromboembolism.
The aetiology of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown and may be heterogeneous, because there are several ethnic differences in the clinical characteristics of CTEPH. Female predominance and a higher ratio of chronic to acute pulmonary thromboembolism have been reported in Japan as compared with the USA. Because such ethnic differences may be controlled by genetic factors, the current study investigated HLA polymorphisms in Japanese patients with CTEPH. HLA typing by serological and/or DNA typing methods was performed (for HLA-A, B, DPB1, DRB1) in 80 patients and 678 controls, and the association of clinical characteristics with HLA alleles was studied. The frequencies of HLA-B*5201 (40 versus 24%) and DPB1*0202 (19 versus 6%) were significantly higher in the patients. HLA-B*5201 positive patients showed a significant female predominance. Total pulmonary vascular resistance and mixed venous oxygen tension were better in the HLA-B*5201 positive patients. In contrast, cardiac index and gas exchange parameters were worse in the HLA-DPB1*0202 positive patients. In the patients carrying HLA-B*5201 and/or -DPB1*0202, the frequency of deep vein thrombosis was significantly lower than the other patients. These observations suggested that both the susceptibility and clinical characteristics of chronic thromboembolic pulmonary hypertension were controlled in part by the HLA-B and -DPB1 loci.
Adult↗
Increase of laminin 5 synthesis in human keratinocytes by acute wound fluid, inflammatory cytokines and growth factors, and lysophospholipids.
BACKGROUND: Laminin 5 is known to induce the adhesion, spreading and migration of human keratinocytes. In skin wound healing, laminin 5 deposition beneath migrating keratinocytes occurs early and is followed by the formation of hemidesmosomes and then basement membrane. OBJECTIVES: To identify factors that regulate the synthesis and secretion of laminin 5 by human keratinocytes during acute wound healing. METHODS: Laminin 5 synthesis by human keratinocytes was determined by a specific sandwich enzyme-linked immunosorbent assay. To determine the total amount of laminin 5 synthesized, laminin 5 deposited on culture dishes and inside cells was solubilized by detergent solution and determined separately from conditioned medium, and the total laminin 5 synthesis was calculated. A quantitative polymerase chain reaction method was used to measure the expression levels of laminin 5 genes, LAMA3, LAMB3 and LAMC2, which correspond to the alpha3, beta3 and gamma2 chains of laminin 5. We also examined the effects of lysophospholipids, proinflammatory cytokines and growth factors, which are components in acute wound fluids, on laminin 5 synthesis in keratinocytes. RESULTS: Human acute wound fluid at days 1, 2 and 3 stimulated laminin 5 synthesis in cultured human keratinocytes in a concentration-dependent manner, although findings are restricted to one case. Human serum also increased laminin 5 production by human keratinocytes as strongly as the wound fluid did, suggesting that the major active components in acute wound fluid may be derived from those in human serum. Lysophospholipids such as lysophosphatidic acid (LPA), lysophosphatidylcholines (LPCs) and sphingosine-1-phosphate (S1P) increased laminin 5 synthesis in a concentration-dependent manner. Among growth factors, epidermal growth factor, insulin-like growth factor-1, interferon-gamma and keratinocyte growth factor increased laminin 5 production in keratinocytes, while platelet-derived growth factor, hepatocyte growth factor and basic fibroblast growth factor were ineffective. Although interleukin-1alpha had no effect, transforming growth factor (TGF)-alpha, tumour necrosis factor (TNF)-alpha and TGF-beta1 also stimulated laminin 5 synthesis, and TGF-alpha and TGF-beta1 showed a synergistic effect. Neutralizing antibodies to TGF-alpha and TGF-beta1 markedly inhibited the enhanced laminin 5 synthesis by human serum, suggesting that TGF-alpha and TGF-beta1 are important components to increase laminin 5 in human serum. In line with the increase of laminin 5 synthesis, the expression levels of all three laminin 5 genes were also augmented by TGF-alpha and TGF-beta1. CONCLUSIONS: Laminin 5 synthesis in human keratinocytes was augmented by inflammatory cytokines and growth factors such as TGF-alpha, TGF-beta1 and TNF-alpha, and lysophospholipids such as S1P, LPA and LPCs, which are supposed to be present in acute wound fluid. The increased laminin 5 protein in the wound area presumably enhances wound repair by stimulating adhesion and migration of keratinocytes on the wound bed and by facilitating basement membrane formation at the dermal-epidermal junction.
Cell Adhesion Molecules↗
Development and progression of diabetic retinopathy in patients with Type 1 diabetes who are positive for GAD autoantibody.
AIMS: To investigate the relationship between autoantibodies to glutamic acid decarboxylase (GAD) and proliferative diabetic retinopathy (PDR) to assess the role of autoimmunity in retinopathy. METHODS: Patients with Type 1 diabetes for more than 10 years who had been diagnosed under age 30 (13-28 years) were studied. They were classified into three groups. The PDR group consisted of 22 patients, the pre-PDR group was 26 patients, while the non-DR group was 32 patients who had Type 1 diabetes without retinopathy. Blood was collected to measure autoantibodies to GAD, and the relationship between PDR and GAD positivity was investigated in a cross-sectional study. RESULTS: The highest positivity rate of GAD autoantibodies was 50.0% in the non-DR group, followed by the pre-PDR group (30.8%) and the PDR group (18.2%). CONCLUSIONS: Production or existence of GAD autoantibodies may contribute to the prevention of retinopathy.
Adolescent↗
HLA typing is not predictive of proliferative diabetic retinopathy in patients with younger onset type 2 diabetes mellitus.
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Adult↗
Pigment epithelium-derived factor prevents advanced glycation end products-induced monocyte chemoattractant protein-1 production in microvascular endothelial cells by suppressing intracellular reactive oxygen species generation.
AIMS/HYPOTHESIS: Monocytes and macrophages accumulate in the lesion of the diabetic retina, which are most likely involved in the progression of diabetic retinopathy. The levels of monocyte chemoattractant protein-1 (MCP-1) in vitreous fluids were associated with the severity of proliferative diabetic retinopathy. Recently, pigment epithelium-derived factor has been shown to be involved in the pathogenesis of proliferative diabetic retinopathy. However, a role of pigment epithelium-derived factor in monocyte recruitments in diabetic retinopathy remains to be elucidated. In this study, we investigated effects of purified pigment epithelium-derived factor on AGE-induced reactive oxygen species generation, MCP-1 mRNA up-regulation and protein production in human cultured microvascular endothelial cells. METHODS: The intracellular formation of reactive oxygen species was measured using the fluorescent probe CM-H(2)DCFDA. MCP-1 gene expression was analysed in quantitative reverse transcription-polymerase chain reaction. Monocyte chemoattractant protein-1 production by microvascular endothelial cells was measured with an ELISA system. RESULTS: AGE increased intracellular reactive oxygen species generation in microvascular endothelial cells. Pigment epithelium-derived factor inhibited the AGE-induced reactive oxygen species generation in a dose-dependent manner. An anti-oxidant, N-acetylcysteine, or pigment epithelium-derived factor completely prevented the AGE-induced up-regulation of MCP-1 mRNA contents as well as protein production in microvascular endothelial cells. CONCLUSIONS/INTERPRETATIONS: Pigment epithelium-derived factor inhibits the AGE-induced reactive oxygen species generation and the subsequent increase in MCP-1 production in microvascular endothelial cells. Our study suggests that substitution of pigment epithelium-derived factor could prevent the progression of diabetic retinopathy by attenuating the deleterious effects of AGE.
Cells, Cultured↗
Can we identify novel angiogenesis inhibitors from cultured embryonic cells?
The first vascular structures in embryos are formed by vasculogensis, the de novo formation of blood vessels from angioblasts. However, angiogenesis, the sprouting of capillaries from pre-existing blood vessels, are also involved in the development of embryonic vascular system in certain organs, such as the kidney or the brain. These facts led us to speculate that embryonic tissues could produce potent angiogenesis inhibitors as well to refine the primitive vascular development. In the present study, we found that two different types of cultured human embryonic cells, 293T and WI-38, produced soluble factors that completely inhibited angiogenic effects of vascular endothelial growth factor on microvascular endothelial cells. Since angiogenesis is related to various pathological states, including tumor growth and metastasis and diabetic retinopathy, to identify novel potent angiogenesis inhibitors from cultured embryonic cells by differential display techniques or DNA microarray technology might be a valuable strategy to develop a novel therapeutic approach.
Angiogenesis Inhibitors↗
Polymorphisms of sorbitol dehydrogenase (SDH) gene and susceptibility to diabetic retinopathy.
The polyol pathway consists of two enzymes aldose reductase (AR) and sorbitol dehydrogenase (SDH); the former is the first enzyme in the polyol pathway, that catalyzes the reduction of glucose to sorbitol, the latter is the second one, that converts sorbitol to fructose using by NAD(+) as a cofactor. We along with others have recently found that SDH activity, the second step in the polyol pathway, might make a greater contribution to the etiology of diabetic retinopathy than does the first step involving AR. In this paper, we propose a novel hypothesis that polymorphisms of SDH gene may be correlated with SDH gene expression levels in diabetic retinas, thus being a valuable genetic marker for diabetic retinopathy.
Aldehyde Reductase↗
Chemical peeling with salicylic acid in polyethylene glycol vehicle suppresses skin tumour development in hairless mice.
BACKGROUND: Chemical peeling with salicylic acid in polyethylene glycol (PEG) vehicle is used clinically to improve the cosmetic appearance of skin that has been damaged by exposure to the sun. It is well known that cancers of the skin such as basal cell carcinoma and squamous cell carcinoma may be induced by the sun. However, the carcinogenic potential of chemical peeling agents has not been studied. OBJECTIVES: To evaluate the effects of chemical peeling with 30% salicylic acid in PEG on skin tumour formation in treated vs. control mice. METHODS: To serve as a model of sun-damaged skin, hairless SKH/hr1 mice were irradiated with ultraviolet (UV) B for 14 weeks, with or without treatment every 2 weeks with 30% salicylic acid in PEG for a total of 18 weeks. RESULTS: Not only was the total number of tumours greatly reduced in the treated vs. the control mice, but skin tumour development was also slower in the treated vs. the control mice. At the final treatment, the fractions of T and B lymphocytes and natural killer cells from spleens of both groups of mice were comparable, and interferon-gamma production did not differ. CONCLUSIONS: Our findings suggest that chemical peeling with salicylic acid in PEG may help to prevent as well as to reduce the number of UVB-induced skin tumours.
Animals↗
Evaluation of autologous cultured epithelium as replacement skin after tattoo excision: correlation between skin texture and histological features.
BACKGROUND: Cultured epidermal autographs (CEAs) are currently used as a coverage treatment for burn wounds, for disfiguring burn scars involving depigmentation and in restoring the elasticity of the skin. The advantage of CEAs is that epidermal sheets prepared from small skin pieces can be enlarged sufficiently to cover large burn areas. OBJECTIVES: We examined the correlation between recovery of skin texture, and elastic fibre formation and keratinocyte differentiation (assessed by immunohistochemistry) in CEAs used as replacement skin after tattoo excision in a Japanese patient. METHODS: The tattooed skin was excised down to the deep dermal layer and then CEA was transplanted onto the patient. The skin textures were evaluated by taking replicas of the skin surface, and histological changes of filaggrin, transglutaminase, involucrin, fibrillin and elastin in the autograft skin were examined by immunohistochemistry. RESULTS: The skin texture improved with time after grafting the CEA, and appeared similar to that of normal skin at 39 months. Among keratinocyte differentiation markers, filaggrin recovered to a normal pattern at around 6 months, and transglutaminase did so at 39 months, whereas involucrin expression remained abnormal at 39 months. Fibrillin expression appeared similar to that of normal skin by 39 months, except for sparse candelabra-like structures of short fibres. Elastin expression remained at a low level throughout. CONCLUSIONS: Our results show that the recovery of skin texture after application of CEAs following tattoo excision is associated with the normalization of epidermal differentiation markers, except involucrin, and with the regeneration of elastic fibres in the dermis.
Adult↗
N-acetylglucosamine-phosphate mutase genotype and diabetic microvascular complications.
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Acetylglucosamine↗
Angiotensin II-type 1 receptor interaction upregulates vascular endothelial growth factor messenger RNA levels in retinal pericytes through intracellular reactive oxygen species generation.
The renin-angiotensin system has been implicated in the development and progression of atherosclerosis, thereby contributing to adverse cardiovascular events. However, its role in diabetic retinopathy remains to be elucidated. Since pericyte loss and dysfunction have been considered as one of the characteristic changes of the early phase of diabetic retinopathy, we investigated the effects of angiotensin II (Ang II) on the growth and function of bovine cultured retinal pericytes. Ang II stimulated intracellular reactive oxygen species (ROS) generation in pericytes in a dose-dependent manner. Telmisartan, a newly developed Ang II type 1 receptor antagonist, completely inhibited ROS generation in pericytes induced by Ang II. Ang II decreased DNA synthesis in pericytes, which was significantly prevented by an antioxidant N-acetylcysteine. Furthermore, telmisartan or N-acetylcysteine were found to completely inhibit the Ang II-induced upregulation of vascular endothelial growth factor messenger RNA levels in pericytes. The present results suggest that Ang II-type 1 receptor interaction could induce pericyte loss and dysfunction through intracellular ROS generation, thus being involved in the development and progression of diabetic retinopathy.
Acetylcysteine↗