UMLS:C0086543 - FACTA Search

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Query: UMLS:C0086543 (cataract)
29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human lenses contain many photosensitizers that absorb light at wavelengths above 300 nm, most notably UVA light (320-400 nm). Kynurenine (Kyn) and 3-hydroxykynurenine (HK), two of the best-known photosensitizers in the human lens, may play a significant role in photooxidation-related changes in lens proteins, such as conformational change and aggregation. In vitro irradiation experiments with proteins indicate that the Trp residue (with maximal absorption at 295 nm) is more susceptible to photooxidation by UVB light (280-320 nm) than by UVA light, but most UVB light below 300 nm is screened by the cornea and little reaches the lens, especially the nuclear region where nuclear color develops. Therefore, if photooxidation is an important contributor to nuclear color or nuclear cataract, it must arise from a photosensitized reaction. In the present study, we use recombinant alpha A- and its Trp-deficient mutant W9F as models to study the effects of UVA irradiation in the presence of HK or Kyn and of UVB (300 nm) irradiation on alpha-crystallins. alpha A-crystallin showed a large decrease in Trp fluorescence and a large increase in non-Trp (blue) fluorescence after the HK-sensitized or 300 nm photooxidation. For the W9F mutant, a smaller decrease in protein fluorescence (lambda ex at 280 nm) and a smaller increase in blue fluorescence than for the wild-type alpha A-crystallin were observed. A decrease in the near-UV CD was also observed for both photooxidized alpha A and the W9F mutant. The effect of Kyn sensitization is smaller than that of HK sensitization. A study of chaperone-like activity indicated that only 300 nm photooxidized alpha A and the W9F mutant increased the ability to protect insulin from dithiothreitol-induced aggregation. Thus, sensitized photooxidation can occur in amino acids other than Trp by UVA in the presence of HK or Kyn with effects similar to, albeit smaller than, those of direct UVB (300 nm) photooxidation.
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PMID:Photooxidized products of recombinant alpha A-crystallin and W9F mutant. 1008 24

A point mutation of a highly conserved arginine residue in alphaA and alphaB crystallins was shown to cause autosomal dominant congenital cataract and desmin-related myopathy, respectively, in humans. To study the structural and functional consequences of this mutation, human alphaA and alphaB crystallin genes were cloned and the conserved arginine residue (Arg-116 in alphaA crystallin and Arg-120 in alphaB crystallin) mutated to Cys and Gly, respectively, by site-directed mutagenesis. The recombinant wild-type and mutant proteins were expressed in Escherichia coli and purified. The mutant and wild-type proteins were characterized by SDS-polyacrylamide gel electrophoresis, Western immunoblotting, gel permeation chromatography, fluorescence, and circular dichroism spectroscopy. Biophysical studies reveal significant differences between the wild-type and mutant proteins. The chaperone-like activity was studied by analyzing the ability of the recombinant proteins to prevent dithiothreitol-induced aggregation of insulin. The mutations R116C in alphaA crystallin and R120G in alphaB crystallin reduce the chaperone-like activity of these proteins significantly. Near UV circular dichroism and intrinsic fluorescence spectra indicate a change in tertiary structure of the mutants. Far UV circular dichroism spectra suggest altered packing of the secondary structural elements. Gel permeation chromatography reveals polydispersity for both of the mutant proteins. An appreciable increase in the molecular mass of the mutant alphaA crystallin is also observed. However, the change in oligomer size of the alphaB mutant is less significant. These results suggest that the conserved arginine of the alpha-crystallin domain of the small heat shock proteins is essential for their structural integrity and subsequent in vivo function.
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PMID:Structural and functional consequences of the mutation of a conserved arginine residue in alphaA and alphaB crystallins. 1044 86

Diabetic retinopathy (DR) is amenable to good diabetic control; however, only successful pancreas transplantation can achieve sustained normoglycaemia. The aim of this long-term study was to examine the course of DR in insulin-dependent diabetic recipients of a simultaneous kidney and pancreas transplant (SPK). Successful SPK recipients (n = 46) and failed pancreas transplant with a functioning kidney transplant (n = 8) were assessed by baseline and regular post-transplant ophthalmic examinations (n = 432) for up to 10 yr after SPK. At the time of SPK (n = 108 eyes), the mean duration of diabetes was 25 +/- 7 yr, ten eyes were blind, and 79% of eyes had advanced DR that had panretinal laser (panretinal photocoagulation, PRP. Successful SPK recipients had normal glucose control with a mean HBA1C of 5.2 +/- 0.6%. DR remained stable in 75% of both the study and control groups, with no difference between groups. The DR mostly evolved towards inactive proliferative DR. After SPK, 14% of non-blind eyes showed improvement of DR, 76% remained stable and 10% progressed. Early vitreous haemorrhage occurred in 6.1% of eyes, and was related to established DR. Cataract of all types increased after transplantation (p < 0.01), which reduced visual acuity (VA) in affected eyes. The mean overall VA remained unchanged for the study duration. In summary, uremic patients from diabetic nephropathy had a high prevalence of severe proliferative DR and blindness at the time of presentation for SPK. This was subsequently stabilised to inactive proliferative DR by appropriate laser therapy followed by metabolic control achieved by SPK.
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PMID:Diabetic retinopathy after combined kidney-pancreas transplantation. 1048 79

The authors present a case report of a 13.5 yrs old girl. The first manifestation of her diabetes was the sudden decrease of her vision due to bilateral cataract. There was no report of perinatal of actual infection, previous trauma, radiation exposure or drug consumption. She was hypermetropic, for that she regularly underwent ophthalmological examination, including fundoscopy. In the patient's history the usual presenting signs of diabetes i.e. weight loss, polyuria, polydipsia, weakness were absent. Upon admission in the hospital, blood sugar was 32.3 mmol/l, HbAIC 12.3%. After correction of her mild ketoacidosis and controlling her elevated serum glucose level she undervent bilateral cataract phacoemulsification, and artificial lens implant on day 14th and 58th. The patient regained her previous visual acuity, while her diabetes was controlled with 0.83 IU/kg/day of insulin. In the Hungarian literature the authors did not find any similar case. In the literature 22 similar cases were described.
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PMID:[Acute metabolic cataract as a first manifestation of IDDM in an adolescent girl]. 1050 80

Cataract is a frequent ocular complication in diabetic patients, but few data are available concerning early modifications occurring in the lens of these patients and their relationship with metabolic control and other clinical parameters. We measured lens opacity in 73 type I, insulin-dependent diabetic patients aging 50 years or less and without clinical evidence of cataract, and in 46 healthy volunteers of similar age. We used a quick, simple, and reliable instrument, the Lensmeter 701, which is based on a back-light scattering quantification system and is able to quantify lens transparency along the nuclear axis. Mean lens opacity was significantly (p = 0.0001) higher in diabetic patients than in the control group, and multiple regression analysis showed that it correlated with age (p = 0.0001) and HbA1c levels (p = 0.009). Moreover in the younger group of patients (age < or =20 years) the only observed correlation was that with Hba1c (p = 0.03), whereas in the older ones (age 21-30 and >30 years) lens opacity correlated with age (p = 0.02 and p = 0.01). These data indicate that early opacifications of the lens occur in type I, insulin-dependent diabetic patients and are influenced by the degree of the metabolic control in the younger ones, whereas the well-known role of aging on lens transparency became prevalent in the older patients. Only longitudinal studies, however, can demonstrate whether these alterations represent any early stage of cataractagenesis and the role of good metabolic control in preventing this ocular complication.
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PMID:Age and metabolic control influence lens opacity in type I, insulin-dependent diabetic patients. 1050 76

beta-Carbolines are tricyclic nitrogen heterocycles formed in plants and animals as Maillard reaction products between amino acids and reducing sugars or aldehydes. They are being detected increasingly in human tissues, and their physiological roles need to be understood. Two beta-carboline carboxylates have been reported to accumulate in the human eye lens. We report here on the identification of another beta-carboline, namely 1-methyl-1-vinyl -2, 3,4-trihydro-beta-carboline-3-carboxylic acid, in the lenses of some cataract patients from India. Analysis of these three lenticular beta-carbolines using photodynamic and antioxidant assays shows all of them to be inert as sensitizers and effective as antioxidants; they quench singlet oxygen, superoxide and hydroxyl radicals and inhibit the oxidative formation of higher molecular weight aggregates of the test protein, eye lens gamma-crystallin. Such antioxidative ability of beta-carbolines is of particular relevance to the lens, which faces continual photic and oxidative stress. The beta-carboline diacid IV is also seen to display an unexpected ability of inhibiting the thermal coagulation of gamma-crystallin and the dithiothreitol-induced precipitation of insulin. These results offer experimental support to earlier suggestions that one of the roles that the beta-carbolines have is to offer protection against oxidative stress to the human tissues where they accumulate.
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PMID:beta-carbolines that accumulate in human tissues may serve a protective role against oxidative stress. 1064 99

The incidence of and risk factors for cataract during a mean (standard deviation (SD)) follow-up period of 5.0 (3.0) (range 0.1-12.4) years were examined among 3606 patients (2001 male and 1605 female) with diabetes mellitus from three outpatient clinics at the University Hospital, Nottingham. Among the 3606 patients free of cataract at initial registration who attended the clinic at least twice in the period 1979-1992, the mean (SD) age was 49.2 (17.8) years with a mean (SD) duration of diabetes of 7.6 (9.8) years at initial registration. The incidence of cataract was 10.4 (95% confidence interval (CI), 9.0, 11.9) per 1000 person-years based on 18089 person-years of follow-up. The incidence for females (13.6 (95% CI, 11.0, 16.1)) was greater than in males (8 (95% CI, 6.3, 9. 7)) (P<0.001). The incidence of cataract in insulin-dependent diabetes mellitus (IDDM), non-insulin-treated and insulin-treated non-insulin-dependent diabetes mellitus (NIDDM) were 7.1 (95% CI, 5. 4, 8.9), 11.7 (95% CI, 9.1, 14.3) and 17.8 (95% CI, 12.9, 22.7) per 1000 person-years, respectively. Age-adjustment substantially changed the ordering of risk associated with different types of diabetes. Using a Cox's Proportional Hazards Model for IDDM and NIDDM (insulin and non-insulin-treated) diabetes separately, age and any retinopathy were significant independent predictors of cataract for all groups. Poor metabolic control also was a significant independent predictor of cataract for the IDDM and insulin-treated NIDDM diabetes groups. Duration of diabetes was a significant independent predictor of cataract for the IDDM group. Age at diagnosis of diabetes, systolic and diastolic blood pressure, body mass index, proteinuria, cigarette smoking and creatinine had no significant independent association with cataract when other covariates were considered. These findings will help the identification of those diabetic patients at particular risk of cataract so that clinic time for screening of eyes can be appropriately focused and health care planning for people with diabetes considered.
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PMID:Incidence of and risk factors for cataract among diabetes clinic attenders. 1065 68

An autosomal dominant congenital cataract in human is associated with mutation of Arg-116 to Cys (R116C) in alpha A-crystallin. To investigate the molecular basis of cataract formation, rat alpha A-crystallin cDNA was cloned into pET-23d(+), and the site-directed mutants S142C (similar to wild-type human alpha A) and R116C/S142C or R116C (similar to human R116C variant) were generated. These were expressed in E. coli and the recombinant alpha A-crystallins purified by Sephacryl size-exclusion chromatography. The chaperone-like function of mutant R116C determined at 37 degrees C with insulin and alcohol dehydrogenase as target proteins was about 40% lower than those of wild-type and mutant S142C. Based on size-exclusion chromatography data, the oligomeric size of the R116C mutant was about 2000 kDa at 25 degrees C, 1400 kDa at 37 degrees C, and 900 kDa at 45 degrees C. In comparison, alpha A-wild-type and alpha A-S142C ranged from 477 to 581 kDa. Heat stability studies corroborated the effect of temperature on the dynamic quaternary structure of the R116C mutant. Circular dichroism spectra showed secondary and tertiary structural changes, and ANS fluorescence spectra showed loss of surface hydrophobicity in the R116C mutant. These findings suggest that the molecular basis for the congenital cataract with the alpha A-R116C mutation is due to the generation of a highly oligomerized alpha A-crystallin having a modified structure and decreased chaperone-like function.
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PMID:Mutation of R116C results in highly oligomerized alpha A-crystallin with modified structure and defective chaperone-like function. 1068 23

Explanted newborn rat lens epithelial cells were cultured with various concentrations of FGF-2 and/or insulin or IGF-I for 8-20 days. The accumulation of alphaA-, alphaB-, betaA3/1-, betaB2- and gammaA-F-crystallin was measured. During culture with insulin only, i.e. in the absence of fibre cell differentiation, alphaA- and alphaB-crystallin accumulated to the same level as found in differentiating cells. Culture of epithelial cells with IGF-I led to an increase in alphaB-crystallin, but not in alphaA-crystallin. The addition of insulin under differentiation conditions (in the presence of 25 ng ml(-1)FGF-2) augmented the accumulation of alphaA-crystallin 1.5-fold, the accumulation of betaB2-crystallin two-fold and the accumulation of gammaA-F-crystallin five-fold over that found with FGF-2 only. The accumulation of alphaB- and betaA3/1-crystallin was not affected by insulin in the presence of FGF-2. Adding IGF-I to fibre cells differentiating in the presence of 25 ng ml(-1)FGF-2 resulted in a 1.5-fold increase (of questionable statistical significance) in both alphaA- and alphaB-crystallin and a two to three-fold increase in gammaA-F-crystallin compared to cells cultured with FGF-2 only, no significant effect of IGF-I on the accumulation of betaA3/1- or betaB2-crystallin was found. Comparison of the levels of mRNA and protein suggests that insulin acts to increase the level of transcription. Our results show that the response of fibre cells to insulin or IGF-I differs. Hence, even though half the maximum dosage required for the insulin effect was rather high (between 0.1 and >5 micro g), the effect of insulin cannot be merely transmitted by the IGF-I receptor. Our data further predict that insulin or IGF-I increases the overall ratio of beta- and gamma-crystallin to alpha-crystallin in the fibre cell, which could predispose the lens to cataract.
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PMID:Insulin and IGF-I affect the protein composition of the lens fibre cell with possible consequences for cataract. 1084 83

Diabetes mellitus is one of the most common endocrinopathies in the dog and cat. Diabetic cataract primarily affects the canine species and is rarely observed in the cat. It has been proposed that the incidence of cataracts in diabetic dogs is high because many of these patients have significant hyperglycemia despite insulin therapy. Age, gender, levels of serum glucose (before and during insulin therapy) and cataract formation were evaluated, retrospectively, in 23 dogs and 22 cats with diabetes mellitus. In the canine population, the groups with the highest frequency of presentation were females and sexually intact animals. In contrast, males and neutered animals were the most prevalent groups in the feline diabetic population. Over 80% of diabetic cats and dogs were older than 7 years. Our results confirm the almost total lack of cataracts in diabetic cats, while they were present in more than half of the dogs. A relation between the incidence of cataracts and the correspondent level of hyperglycemia in the canine and feline species could not be established. The estimation of the relative risk for the development of cataracts in diabetic dogs shows that some population groups have a higher probability for suffering from this ocular alteration. A relation between relative risk and the correspondent level of hyperglycemia in the various groups was not found. This fact indicates that other factors are involved in the unequal appearance of diabetic cataracts in dogs and cats.
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PMID:Diabetic cataracts: different incidence between dogs and cats. 1089 2

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