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J A Olson

Publications and source records attributed to J A Olson.

At least 55 records · Page 3Linked to original sources
PubMed1998

A comparison of computer based classification methods applied to the detection of microaneurysms in ophthalmic fluorescein angiograms.

We compared the performance of three computer based classification methods when applied to the problem of detecting microaneurysms on digitised angiographic images of the retina. An automated image processing system segmented 'candidate' objects (microaneurysms or spurious objects), and produced a list of features on each candidate for use by the classifiers. We compared an empirically derived rule based system with two automated methods, linear discriminant analysis and a learning vector quantiser artificial neural network, to classify the objects as microaneurysms or otherwise. ROC analysis shows that the rule based system gave a higher performance than the other methods (p = 0.92) although a much greater development time is required.

Aneurysm↗
PubMed1998

Effect of vitamin A deficiency on the hydrolysis of retinoyl beta-glucuronide to retinoic acid by rat tissue organelles in vitro.

In keeping with the in vivo observation that the conversion of retinoyl beta-glucuronide (RBG) to retinoic acid (RA) is enhanced in vitamin A-deficient (A-) rats, the relative rates of hydrolysis of RBG to RA by various organelles of liver, kidney and intestine were found to be higher in A- rats than in vitamin A-sufficient (A+) rats (mean ratio 1.28; range 1.05-1.63). The lysosomal fraction of kidney and the microsomal fraction of liver showed the highest ratios for RBG hydrolysis; namely, 1.63 and 1.57, respectively (p < 0.005). The rates of hydrolysis of an ether glucuronide, p-nitrophenyl-beta-D-glucosiduronate (pNPG), were also enhanced in A- rats. The ratios of activities were again highest in kidney lysosomes and in liver microsomes; namely, 1.51 (p < 0.005) and 1.42 (p < 0.05), respectively. The non-ionic detergent, Triton X-100, increased RBG hydrolysis in organelles of A+ (19-27%) more than in those of A- rats (8-14%). The ratios of activities +/- SEM with 0.02% Triton X-100 in organelles of kidney, liver and intestine were 1.25 +/- 0.03, 1.22 +/- 0.03 and 1.24 +/- 0.03 in A+ rats and were 1.11 +/- 0.02, 1.07 +/- 0.02 and 1.13 +/- 0.03, respectively, in A- rats. Thus, Triton X-100 had a significantly greater effect (p < 0.005) on the membranes of A+ rats than on those of A- rats. In conclusion, the increased appearance of RA in the plasma after RBG administration in vivo seems to be caused by enhanced activity of beta-glucuronidases in tissue organelles, augmented in part by better access of the substrate to the membrane-bound enzymes.

Animals↗
PubMed1997

Repromicin derivatives with potent antibacterial activity against Pasteurella multocida.

Reductive amination of repromicin with polyfunctional amines has led to new macrolide antibacterial agents, some of which are highly potent against the Gram-negative pathogen Pasteurella multocida both in vitro and in a mouse infection model. A key element in this discovery was the recognition that among certain known macrolides increasing lipophilicity results in diminished in vivo activity. One repromicin derivative, 20-[N-[3-(dimethylamino)-propyl]-N-L-alanylamino]-20-deoxorepro micin (35), was selected for advanced evaluation. At 5 mg/kg, a single subcutaneous dose was found to control induced pasteurellosis in swine and induced respiratory disease in cattle.

Animals↗
PubMed1997

Soluble leucocyte adhesion molecules in diabetic retinopathy stimulate retinal capillary endothelial cell migration.

Diabetic retinal neovascularisation is considered to be a consequence of retinal ischaemia caused by capillary occlusion. Capillary occlusion is the result of microvascular thrombi in which erythrocytes, platelets and leucocytes each may play a role. We investigated the role of leucocytes in this process and the subsequent angiogenic response. We studied the serum levels of the soluble leucocyte adhesion molecules soluble E-Selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) in the serum of 93 patients with insulin-dependent diabetes (IDDM) and varying degrees of retinopathy and 47 healthy age and sex matched control subjects. We also measured the ability of serum to stimulate retinal capillary endothelial cell migration using an assay of angiogenesis in vitro. Soluble E-Selectin and sVCAM-1 levels were raised in all patients with IDDM (p < 0.001; p < 0.001) particularly those with retinopathy (p < 0.001; p < 0.001). Soluble E-Selectin levels were highest in the patients with severe non-proliferative diabetic retinopathy (p < 0.001) and sVCAM-1 levels were highest in patients with proliferative diabetic retinopathy (p < 0.01). In contrast soluble ICAM-1 levels were the same in patients and control subjects (p > 0.05). Soluble E-Selectin levels in diabetic patients were correlated with the level of glycated haemoglobin (p < 0.05). Retinal endothelial cell migration-inducing (ECMI) activity was increased in patients with IDDM (p < 0.01) in particular in those with retinopathy (p < 0.01). Furthermore, in vitro ECMI activity could be blocked by antibodies to sVCAM-1 and sE-Selectin. These data point to a functional role for leucocyte adhesion in the microvasculopathy of diabetic retinopathy and may have implications for the induction of retinal angiogenesis.

Adult↗
PubMed1997

A fully automated comparative microaneurysm digital detection system.

A fully automated digital image processing system, which provides an objective and repeatable way to quantify microaneurysms in digitised fluorescein angiograms, has been developed. The automated computer processing includes registration of same-eye retinal images for serial studies, cutting of regions-of-interest centred on the fovea, the detection of microaneurysms and the comparison of serial images for microaneurysm turnover. The microaneurysm detector was trained against a database of 68 images of patients with diabetes containing 394 true microaneurysms, as identified by an ophthalmologist. The microaneurysm detector achieved 82% sensitivity with 2.0 false-positives per image. An independent test set, comprising 20 images containing 297 true microaneurysms, was used to compare the microaneurysm detector with clinicians. The microaneurysm detector achieved a sensitivity of 82% for 5.7 false-positives per image, whereas the clinician receiver-operator-characteristic (ROC) curve gives 3.2 false-positives per image at a sensitivity of 82%. It is concluded that the computer system can reliably detect microaneurysms. The advantages of the computer system include objectivity, repeatability, speed and full automation.

Aneurysm↗
PubMed1997

Vitamin A and vitamin E statuses of preschool children of socioeconomically disadvantaged families living in the midwestern United States.

OBJECTIVE: To determine the vitamin A and vitamin E statuses of socioeconomically disadvantaged preschool American children. DESIGN: Cross-sectional study of preschool children from socioeconomically disadvantaged families. SETTING: Central Iowa, USA. SUBJECTS: A group of 77 apparently healthy children was studied with the following characteristics: 5 mo-6 y; 37 males, 40 females, 56 non-Hispanic Caucasians, 3 Hispanics, 18 Afro-Americans. METHODS: Modified relative dose response (MRDR) test for vitamin A status assessment; serum retinol, alpha-tocopherol, cholesterol, and carotenoids; weight for age. RESULTS: Although the mean weight for age was the 53rd percentile of the NCHS standard, a significant number of children (P = 0.006, chi(2)) were either markedly underweight or overweight. Ratios of 3,4-didehydroretinol to retinol (DR/R) were > 0.030, in 32% of the children. Mean serum retinol, alpha-tocopherol and cholesterol (+/- s.d.) were 1.09 +/- 0.23 microM/L, 16.8 +/- 6.3 microM/L and 4.01 +/- 0.8 microM/L. Three children (3.9%) showed a serum retinol value < 0.7 microM/L. One child with a serum retinol value < 0.7 microM/L and one additional child showed a ratio of alpha-tocopherol to cholesterol < 1.44 mumol/mmol. The mean alpha-tocopherol to cholesterol ratio for the group (4.31 +/- 1.71 mumol/mmol), however, was satisfactory. The only significant (P < or = 0.05) age-related changes were an increase in the serum cholesterol (P = 0.005) and decrease in the alpha-tocopherol to cholesterol ratio (P < 0.005) between the 0-2 y and the 2-4 y groups. Serum cholesterol (P = 0.0165, two-tailed) and lycopene (P = 0.004) concentrations of Afro-Americans were significantly higher than those of Caucasians. Median serum concentrations of alpha-carotene and beta-carotene were lower and, of lycopene higher than those found in children studied in a national survey. Serum carotenoid concentrations generally increased with age. CONCLUSIONS: Larger percentages of underweight and overweight children and a significant degree (32%) of inadequate vitamin A status were found in this group of socioeconomically disadvantaged children. Afro-Americans showed higher serum cholesterol and lycopene concentrations than did Caucasians, but otherwise were nutritionally similar. Age-related changes were small. Of nutritional parameters considered, the vitamin A status of socioeconomically disadvantaged segments of our population clearly needs attention.

Black People↗
PubMed1997

Reduction of serum retinol levels following a single oral dose of all-trans retinoic acid in humans.

Following a single oral dose of all-trans retinoic acid (RA) (0.167 mmole) in corn oil to 6 healthy human subjects, the mean serum retinol (ROL) level fell by approximately 20% within 1 h and remained depressed for 24 h. After dosing, RA appeared in the blood within 30 min, peaked at 0.3-0.5 mumol/l, and then declined to very low concentrations after 7 h. All-trans retinoyl beta-glucuronide (RAG) appeared simultaneously with RA in the plasma, albeit more sporadically, whereas only traces of 4-oxoretinoic acid (4-oxoRA) were detected. Some possible physiologic consequences of therapeutic uses of all-trans RA are discussed.

Adult↗
PubMed1996

Stoichiometric conversion of all trans-beta-carotene to retinal by pig intestinal extract.

beta-Carotene and other provitamin A carotenoids are major dietary sources of vitamin A for humans and for many animals throughout the world. Two pathways for this oxidative reaction in mammals are: (1) central cleavage by beta-carotene 15,15'-dioxygenase (EC 1.13.11.21) to yield two molecules of retinal per molecule of beta-carotene consumed and (2) eccentric (or random) cleavage via several beta-apo carotenals to yield one molecule of retinal and various smaller fragments per molecule of beta-carotene oxidized. By the use of improved methods to minimize nonenzymatic reactions and to measure isomers of retinal, the mean experimentally measured molar ratio of retinal formed to beta-carotene consumed by pig intestinal preparations (800 and 10,000g supernatants) was 1.88 +/- 0.08, close to the theoretical value of 2.0 for central cleavage. beta-Apo carotenals, retinol, and retinoic acid were detected, if at all, in trace amounts during incubation. Thus, preparations of pig intestinal mucosa, which is considered a good physiologic model for human intestine, clearly convert beta-carotene to retinal, in large part if not solely, by central cleavage. Whether eccentric cleavage plays a greater role in vivo than it does in vitro is still uncertain.

Animals↗
PubMed1996

Formation of beta-glucuronides and of beta-galacturonides of various retinoids catalyzed by induced and noninduced microsomal UDP-glucuronosyltransferases of rat liver.

The complex of microsomal UDP-glucuronosyl transferases (UGT; EC 2.4.1.17) of rat liver catalyzes the formation of retinoyl beta-glucuronide (RAG) from retinoic acid (RA) and retinyl beta-glucuronide (ROG) from retinol (ROL) in the presence of UDP-glucuronic acid (UDPGA). The relative rates of formation of beta-glucuronides in noninduced microsomes were: 9-cis RA > 13-cis RA > all-trans 4-oxo RA > TTNPB > all-trans RA > CD-367 > 13-cis ROL > 9-cis ROL > acitretin > all-trans ROL. Michaelis constants (KM) for all-trans RA, 13-cis ROL, TTNPB and UDPGA were 130 microM, 300 microM, 210 microM and 2.6 microM, respectively. Galacturonides of RA, but not detectably of ROL, were formed from UDP-galacturonic acid at 11-30% the rate of the beta-glucuronides, whereas UDP derivatives of nonionized sugars did not serve as substrates. Pretreatment of rats with 3-methylcholanthrene markedly increased RAG formation in the absence of detergent (Triton X-100), but less so in its presence. Clofibrate pretreatment doubled the rate of RAG formation, whereas phenobarbital pretreatment showed little effect. N-Ethylmaleimide (5 microM) minimized cis-trans isomerization without significantly affecting glucuronidation. Rates of glucuronidation of retinoids clearly depend both on their isomeric states and on their chemical structures. Different UGT enzymes might well act on different geometric isomers of RA.

Animals↗
PubMed1996

All-trans-retinoyl beta-glucuronide: new procedure for chemical synthesis and its metabolism in vitamin A-deficient rats.

All-trans-retinoyl beta-glucuronide (RAG) was chemically synthesized in high yields (up to 79%) by a new procedure involving the reaction of the tetrabutylammonium salt of glucuronic acid with all-trans-retinoic acid (RA) via the imidazole or triazole derivative. When RAG was fed orally to vitamin A-deficient rats, RA was identified as the major metabolite in the serum within hours of administration of RAG. Very little or no RAG was detected in the serum. Thus RAG, which was not appreciably hydrolysed to RA in vitamin A-sufficient rats [Barua and Olson (1987) Biochem. J. 263, 403-409], was rapidly converted into RA in vitamin A-deficient rats.

Acitretin↗
PubMed1996

Comparative embryolethality and teratogenicity of the all-trans isomers of retinoic acid, 3,4-didehydroretinyl acetate, and retinyl acetate in pregnant rats.

The teratogenic potencies of the all-trans isomers of retinoic acid (RA), 3,4-didehydroretinyl acetate (A2), and retinyl acetate (A1) were compared. Groups of eight timed-pregnant Sprague-Dawley rats were administered single equimolar doses (3.5-352 mumol/kg BW) of the retinoids orally in oil on day 8.5 of pregnancy, and dams and fetuses were sacrificed on day 19. The relative teratogenicity and embryolethality of the three tested retinoids were: RA > A2 > A1. The no-effect level of RA and A2 was 3.5 mumol/kg BW and of A1 was 35 mumol/kg BW. Whereas the adverse effects of RA and A1 were dose dependent, A2 showed biphasic effects, with a peak of embryolethality at 35 mumol/kg BW. Dams also exhibited weight loss and other toxic manifestations from doses of A2 and Ra > or = 35 mumol/kg BW. In dosed dams, (1) Liver concentrations of A1 and A2 increased with the doses of A1 and A2, respectively, (2) RA had little effect on liver A1 except for an increase at the highest toxic dose, and (3) A2 showed a sparing effect on liver A1. RA, although not detected in fetuses from dams treated with A1, was present in significant concentrations (0.5-4.1 nmol/g liver) in fetuses from dams treated with A2. The biphasic change in embryolethality with the dose of A2 correlates with this enhanced concentration of fetal RA. We hypothesize that the actual teratogen in the fetuses of A2-dosed dams is RA. A2 might induce this biphasic effect by inhibiting the catabolism of RA at lower doses and its formation at higher doses.

Animals↗
PubMed1996

An image-processing strategy for the segmentation and quantification of microaneurysms in fluorescein angiograms of the ocular fundus.

Digital image-processing techniques can provide an objective and highly repeatable way of quantifying retinal pathology. This study describes an image-processing strategy which detects and quantifies microaneurysms present in digitized fluorescein angiograms. After preprocessing stages, a bilinear top-hat transformation and matched filtering are employed to provide an initial segmentation of the images. Thresholding this processed image results in a binary image containing candidate microaneurysms. A novel region-growing algorithm fully delineates each marked object and subsequent analysis of the size, shape, and energy characteristics of each candidate results in the final segmentation of microaneurysms. The technique is assessed by comparing the computer's results with microaneurysm counts carried out by five clinicians, using Receiver Operating Characteristic (ROC) curves. The performance of the automated technique matched that of the clinicians' analyses. This strategy is valuable in providing a way of accurately monitoring the progression of diabetic retinopathy.

Algorithms↗
PubMed1996

Daily supplements of vitamin A (8.4 mumol, 8000 IU) improve the vitamin A status of lactating Indonesian women.

The vitamin A statuses of lactating Indonesian women (n = 23) starting at 1-3 mo after delivery were determined at three monthly intervals (times 1, 2, and 3) during lactation and then again (time 4) after they had ingested vitamin A capsules (8.4 mumol, 8000 IU) daily for 35 d. Vitamin A status was determined by using the modified-relative-dose-response (MRDR) test and serum retinol concentrations. The mean MRDR ratio in these women rose from 0.084 +/- 0.047 (time 1) to 0.099 +/- 0.045 (time 2) and then to 0.100 +/- 0.054 (time 3). After supplementation the mean MRDR ratio fell to 0.040 +/- 0.021 (time 4) (P < 0.0001). Mean serum retinol concentrations at the first three times were 0.94 +/- 0.23, 0.87 +/- 0.20, and 0.80 +/- 0.20 mumol/L, but then rose to 1.10 +/- 0.31 mumol/L at time 4 (P < 0.04). After supplementation mean MRDR values and mean serum retinol concentrations were 60% lower and 38% higher, respectively, than those just before supplementation, MRDR values better distinguished the vitamin A statuses of the women than did serum retinol concentrations. Mean hemoglobin values increased during the study from 118 +/- 9 g/L at time 1 to 122 +/- 6 g/L at time 4 (P = 0.0187). The mean hematocrit also rose from 0.35 +/- 0.03 at time 1 to 0.361 +/- 0.17 at time 4 (P = 0.0478). Thus, iron status may also have improved marginally from time 1 to time 4, but most of the increase appeared before the vitamin A intervention.

Adolescent↗
PubMed1996

Refinement of the modified-relative-dose-response test as a method for assessing vitamin A status in a field setting: experience with Indonesian children.

The modified-relative-dose-response (MRDR) test, which has been used extensively throughout the world for assessing vitamin A status, has been simplified. The major methodologic change resulting from the current studies in Indonesia is the use of graded standard doses of 3,4-didehydroretinyl acetate (DRA) based on the age range of the population of interest. Instead of a dose of 0.35 mumol/kg body wt, standard doses of 5.3 mumol for children younger than 6 y, 7.0 mumol for children between 6 and 12 y of age, and 8.8 mumol for adults and children > 12 y of age are suggested for field use. The acceptable time between administering the oral dose and obtaining a blood sample was validated as being 4-7 h in a group of children (n = 84) by taking two blood samples per child between 3 and 7 h after dosing with DRA. Furthermore, DRA in vitamin E-containing corn oil, with or without the addition of 4.6 mmol all-rac-alpha-tocopheryl acetate/L, was found to be stable for > or = 18 mo at 2 degrees C and at -20 degrees C, but not at 22 degrees C or at 37 degrees C. When DRA was stored in amber glass vials, stability was affected more by temperature than by exposure to room light. In keeping with earlier studies in adults, the ratio of 3,4-didehydro-retinol to retino tends to be independent of body weight. Indeed, slower growing children (ie, those with lower weight-for-age) may have a somewhat better vitamin A status than their heavier counterparts.

Adult↗