Metabolism of vitamin A.
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Acyltransferases↗
Biomedical subjects
J A Olson
Publications and source records attributed to J A Olson.
Retinoyl beta-glucuronide: an endogenous compound of human blood.
The occurrence of retinoyl beta-glucuronide and retinoic acid as normal endogenous components of vitamin A reserve in human blood has been demonstrated. Use of high-performance liquid chromatography, coupled with a sensitive detector and integrator, has enabled us to quantitate nanogram quantities of the two retinoids. Serum concentrations of retinoyl glucuronide and retinoic acid in all the volunteers studied ranged from 1.5 to 5.1 ng/ml (mean 2.42 ng/ml) and from 1.0 to 3.2 ng/ml (mean 1.80 ng/ml) serum, respectively. The identity of retinoyl beta-glucuronide was confirmed by its conversion to retinoic acid by the action of beta-glucuronidase and by study of the mass spectrum of the methylated derivative.
Chromatography, High Pressure Liquid↗
Birefringent hemozoin identifies malaria.
The diagnosis of malaria is still sometimes difficult because of the insensitivity of microscopic screening at low levels of parasitemia. The malarial pigment, hemozoin, is a crystalline product of the digestion of hemoglobin by the parasites. Under polarized light at 500X magnification, brilliantly birefringent granules of the pigment were detected in Wright's stained smears, and the parasites easily localized, in 18 cases of malarial infection. Fresh, wet, coverslipped preparations of cultures of Plasmodium falciparum also were examined under polarized light. Serial dilutions of the cultures showed that, even at the very low level of 0.01% parasitemia, intracellular birefringent granules were detected in an average of 45 +/- 16 (SE) seconds at 500X magnification. Using polarized light is a simple, fast, sensitive, and specific method for localizing intracellular pigmented malaria parasites in wet preparations of blood.
Hemeproteins↗
The rate of rhodopsin regeneration in the bleached eyes of zinc-deficient rats in the dark.
Rats fed a zinc-deficient, phytate-containing diet (ZD rats) for 4 wk showed typical signs of zinc deficiency: reduced food intake, slow weight gain, a poor food efficiency ratio and subnormal zinc concentrations in the serum, femur and eye. Pair-fed, weight-matched rats fed a zinc-sufficient diet (PF rats) showed normal serum zinc values, intermediate femur zinc levels and eye zinc concentrations similar to those in ZD rats. The vitamin A status of all three groups, expressed as the concentration of vitamin A in the liver, was comparable. After extensive bleaching, the initial rate of rhodopsin regeneration in ad libitum-fed, zinc-sufficient rats (AL rats), ZD rats and PF rats was the same, whereas the extent of rhodopsin regeneration in AL rats kept in the dark for 120 min was almost twice that found in ZD and PF rats. These results are not consistent with the hypothesis that zinc deficiency primarily affects dark adaptation by reducing the activity of alcohol dehydrogenase in the eye. Rather, zinc deficiency and the generalized malnutrition that results from markedly reduced food intake seem to depress the synthesis of opsin, and probably other proteins as well, in the rod cells of the eye.
Adaptation, Physiological↗
Carotenoids, vitamin A and cancer.
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Abnormalities, Drug-Induced↗
Recommended nutrient intakes: guidelines for the prevention of deficiency or prescription for total health.
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Adaptation, Physiological↗
Ribose metabolism and nucleic acid synthesis in normal and glucose-6-phosphate dehydrogenase-deficient human erythrocytes infected with Plasmodium falciparum.
The metabolism of pentose-phosphate was investigated in Plasmodium falciparum-infected normal and glucose-6-phosphate dehydrogenase (G6PD)-deficient human red blood cells in vitro. 5'-Phosphoribosyl-1-pyrophosphate (PRPP) content of infected normal red blood cells was increased 50-60-fold at the parasite trophozoite growth stage over that of uninfected cells. The PRPP increment in infected G6PD-deficient cells at comparable stage and parasitemia was only 40% of the value in normal infected cells. Red blood cell PRPP synthetase activity did not change during the growth cycle of the parasite and was similar in both normal and G6PD-deficient cells. Reduced glutathione (GSH) content of G6PD-deficient cells under conditions of culture fell to low or undetectable levels. These low levels of GSH were shown to inhibit the function of red blood cell PRPP synthetase, which requires GSH for full activity. Measurements of the incorporation of 1-14C or 6-14C selectively labeled glucose into parasite nucleic acids revealed that in normal infected red cells, approximately 20% of the pentose was produced via the oxidation of glucose-6-phosphate, whereas in infected G6PD-deficient cells (Mediterranean type), none of the pentose was produced via the oxidative pathway. It is concluded that the low level of reduced GSH found in G6PD deficiency and the resultant partial inhibition of PRPP synthetase together with the missing oxidative pathway for ribose phosphate production can account fully for the reduced parasite growth rate in G6PD-deficient red blood cells described previously. Of these two mechanisms, the predominant one is the impaired PRPP synthetase activity due to low GSH levels in enzyme-deficient red blood cells. The contribution to the ribose-phosphate pool by the hexose monophosphate shunt is relatively minor. A co-existing oxidative stress (which is often hypothesized to mediate the destruction of parasitized red blood cells) is not required to explain growth inhibition in this scheme and does not represent the most straight-forward explanation of the data described in this report.
DNA Replication↗
Humoral responses and cross-reactivity to viridans streptococci in recurrent aphthous ulceration.
It has been proposed that recurrent aphthous ulceration (RAU) is caused by hypersensitivity to oral streptococci. This hypothesis is based on reports that RAU patients have increased levels of circulating IgG antibodies against oral streptococci, and that rabbit antisera prepared against oral streptococci are cross-reactive with oral mucosa. Using indirect immunofluorescence, we have investigated both of these reported phenomena. End-point titers of serum antibodies against three different strains of oral streptococci were assayed from nine RAU subjects with active ulcers and compared with those of nine control subjects. Titers ranged from 1:2 to 1:64 in both groups and do not appear to have any clinical or immunopathogenic significance. Cross-reactivity was studied using hyperimmune rabbit antisera raised against five different strains of oral streptococci. Homologous bacterial titers ranged from 1:1024 to 1:8192, but none of these anti-streptococcal sera produced heterologous titers greater than 1:32 with oral mucosa. This apparent low level of cross-reactivity with oral mucosal antigens appears to be non-specific and clinically insignificant. In previous reports, we have used both leucocyte migration and lymphocyte blast transformation to study cell-mediated immunity to viridans streptococci in RAU (Gadol et al., 1985; Greenspan et al., 1985). None of our results supports an immunopathogenic role for oral streptococci in RAU.
Adult↗
Synchronized cultures of P falciparum in abnormal red cells: the mechanism of the inhibition of growth in HbCC cells.
It has been previously demonstrated that HbCC cells fail to support growth of P falciparum in asynchronous Jensen-Trager cultures. To define the mechanism of inhibition we have studied synchronous cultures and found that while intraerythrocytic parasite development appeared normal, the liberation of merozoites and/or invasion was impaired. This effect was detected by a normal growth during the first growth cycle but dramatically reduced number of ring forms following the schizont stage. A specific test for the invasion of CC cells by P falciparum merozoites, nevertheless, was normal. The defect found in infected CC cells was not modified by changes in O2 tension (which altered the ligand saturation of Hb C) nor by the extracellular K+ concentration (excluding a K+ leak-dependent mechanism for the growth inhibition). The osmotic lysis of late-staged parasitized red cells revealed that 25% of infected AA cells were lysed when the extracellular medium was 95 mOsm. In contrast, infected CC cells required a decrease to 10 mOsm in the extracellular media to reach 25% lysis. We conclude that CC red cells are unsuitable hosts for the malarial parasite primarily because of their inability to lyse and release merozoites at the appropriate stage of intraerythrocytic development of P falciparum.
Animals↗
Enhancement of acyl coenzyme A:retinol acyltransferase in rat liver and mammary tumor tissue by retinyl acetate and its competitive inhibition by N-(4-hydroxyphenyl) retinamide.
Retinol esterification by microsomal acyl coenzyme A:retinol acyltransferase was quantified in rat mammary tumor and liver tissue. Acyltransferase activity in the livers of mammary tumor-bearing rats was 40% of that in normal animals. In response to daily oral doses of 2 mg retinyl acetate for 18-19 days, activity increased 2.8-fold in transplanted rat mammary tumors, 4.1-fold in the livers of tumor-bearing rats, and 1.5-fold in the livers of normal rats. The in vitro esterification of retinol was competitively inhibited by all-trans-N-(4-hydroxyphenyl) retinamide (Ki = 154 microM).
Acyltransferases↗
Proliferative verrucous leukoplakia. A long-term study of thirty patients.
Up to 6% of oral leukoplakia, a relatively common mucosal disease, can be expected to become malignant. This report describes a long-term study of 30 patients in whom a particular form of leukoplakia was identified and labeled proliferative verrucous leukoplakia (PVL), a disease of unknown origin, which exhibits a strong tendency to develop areas of carcinoma. PVL begins as a simple hyperkeratosis but tends to spread and become multifocal. PVL is slow-growing, persistent, and irreversible, and in time areas become exophytic, wartlike, and apparently resistant to all forms of therapy as recurrence is the rule. The disease was most commonly seen in elderly women and had been present for many years. Patients were followed for 1 to 20 years. Thirteen died of or with their disease, 14 were alive with PVL, and 3 were alive without PVL at last contact. PVL rarely regressed despite therapy. All patients who died had persistent or recurrent disease. PVL appears to constitute a continuum of hyperkeratotic disease, ranging from a simple hyperkeratosis at one end to invasive squamous cell carcinoma at the other. Microscopic findings are dependent upon the stage of the disease's development and the location and adequacy of the biopsy.
Adult↗
Leukocyte migration inhibition in recurrent aphthous ulceration.
Leukocyte inhibitory factor (LIF) production in response to streptococcal antigens and oral mucosa was examined as a possible pathogenic mechanism in recurrent aphthous ulceration (RAU). Mononuclear cells from RAU patients and controls were stimulated with antigens prepared from two species of streptococci and from oral mucosa. Candida albicans and foreskin were tested as control antigens. There were some statistically significant differences in leukocyte migration inhibition between patients and controls with some concentrations of Streptococcus sanguis (ATCC 10556) and C. albicans, and a trend toward low migration indices with oral mucosa. However, the roughly equal numbers of patients and controls responding positively to each antigen and the large background variation suggest a lack of biological significance. LIF production did not increase consistently in the early stages and did not correlate with ulcer development in patients studied sequentially. We conclude that LIF production (at least in response to the antigens tested) plays no pathogenic role in RAU. Our data do not support the hypothesis that a specific cell-mediated sensitivity to streptococcal antigens is involved in RAU.
Adult↗
Lymphocyte function in recurrent aphthous ulceration.
Lymphocyte blast transformation responses to mitogens and to streptococcal, adenovirus Type 1, and oral mucosal antigens were studied in 32 patients with recurrent aphthous ulceration (RAU) and matched control subjects. RAU patients showed significantly depressed (p less than 0.05) responses to mitogens in comparison with matched controls, but there was no significant difference between patients and controls in response to any of the antigens tested. These results indicate that neither cell-mediated hypersensitivity to streptococcal or viral antigens nor cross-reactivity between oral mucosal and streptococcal antigens are likely to play a role in the pathogenesis of RAU. Rather, the data support the hypothesis of an imbalance or defect in immune cell subpopulations.
Antigens↗
Basidiomycete allergy: what is the best source of antigen?
Skin prick test activity and antigenicity of extracts of in vitro growth of the Basidiomycete Pleurotus ostreatus (PO) were compared to extracts of spores from PO growing in the wild. Patients demonstrated significant differences in skin test reactivity to the PO extracts. Some reacted only to in vitro growth extracts, others only to the spore extracts and 1 patient to all extracts. Further studies analyzed antigens present in all extracts with rabbit antisera to PO. Common as well as unique antigens were present in the spore extracts as compared to those from in vitro preparations. The fact that spores contain unique antigens suggests that basidiospores may be the best source of relevant allergens for clinical studies.
Antigens, Fungal↗
Calcium requirements and recommended dietary allowances.
Calcium plays an essential role in the regulation of many metabolic processes, in neuromuscular events and in bone health. A number of proteins exist that specifically bind calcium, and calcium markedly influences the activities of many enzymes involved in cellular metabolism and differentiation. Recommended dietary allowances or intakes for calcium vary two-fold, in nearly all age categories in various countries throughout the world. The recommended dietary intake in Japan for most ages is somewhat lower than that in the United States. Median intakes of calcium in the United States decrease after 10 to 20 years of age. Whereas the median calcium intake of adult men approximates the RDA in the United States, that of adult women is considerably lower. The absorption and excretion of calcium are markedly affected, both by physiological and by dietary factors. Calcium intakes required to provide a balanced state in adults vary four-fold, depending on age, sex, diet and hormonal status. Dairy products are the best dietary source of bioavailable calcium. Inasmuch as the median calcium intake of elderly women in the United States is only 60 percent of the RDA, and the same group is highly susceptible to osteoporosis, the calcium intake in this group should probably be increased.
Age Factors↗
Ligand state of intraerythrocytic circulating HbC crystals in homozygote CC patients.
Whole blood and Stractan-Percoll fractions of blood from splenectomized patients with homozygous hemoglobin C (CC) disease were studied under aerobic and anaerobic conditions. Erythrocytes containing typical CC crystals are found in the densest fraction as documented by freeze-fracture electron microscopy. We report that the intraerythrocytic Hb C circulating crystals are in the oxygenated liganded state as demonstrated by melting upon deoxygenation and by absorption spectroscopy. Furthermore, crystals are more likely to form in cells with low concentration of Hb F. Changes of ligand state (which results in melting of the intraerythrocytic crystal) might be involved in the pathophysiology of this disease, removing the danger of vasoocclusive episodes.
Crystallization↗