Current chemotherapeutic treatment strategies in childhood acute nonlymphocytic leukemia.
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Biomedical subjects
Publications and source records attributed to G Jones.
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An infant with propionic acidemia presented at one month of age with hyperammonemic coma. Treatment by two double-volume exchange transfusions did not have an appreciable effect, but hemodialysis led to a substantial reduction of the serum concentration of ammonia on two occasions. Nevertheless, continued therapy with sodium benzoate, arginine-HCl, carnitine and lactulose did not have any observable effect on the blood concentration of ammonia. Treatment with sodium phenylacetate was followed by a reduction in serum concentrations of ammonia to normal levels which were maintained. These observations demonstrate the dramatic reduction in serum concentrations of ammonia that may be obtained in patients with organic acidemia by hemodialysis. They suggest that pharmacologic acylation therapy with phenylacetate may be of lasting benefit in the management of this complication.
Although corticosteroids are effective in the treatment of hypercalciuria and hypercalcemia in chronic sarcoidosis, complications of their long-term use frequently limit therapy. We studied the efficacy of chloroquine in two patients with sarcoidosis who were unable to tolerate the dosage of corticosteroids required to control hypercalciuria and prevent the formation of renal stones. Over a three-year period, each patient received a 6-month and a 10-month course of oral chloroquine phosphate (500 mg per day) while continuing to receive corticosteroids at a fixed dose. Chloroquine therapy was associated with a significant reduction in levels of serum 1,25-dihydroxyvitamin D (1,25(OH)2D) and urinary calcium. We observed a direct correlation between serum 1,25-(OH)2D levels and 24-hour urinary calcium excretion, supporting the hypothesis that excessive serum 1,25-(OH)2D is responsible for the hypercalciuria in sarcoidosis. Serum levels of 25-hydroxyvitamin D (25-(OH)D) did not change with therapy, suggesting that chloroquine may act by inhibiting the conversion of 25-(OH)D to 1,25-(OH)2D. Current dosage guidelines and ophthalmologic-surveillance techniques, which allow chloroquine to be administered with little risk of retinopathy, should permit an expanded role for this agent in the treatment of the calcium abnormalities of sarcoidosis.
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Juvenile hormone esterase (JHE) activity from the hemolymph of larval Trichoplusia ni was analyzed by two different isoelectric focusing (IEF) methodologies. Use of techniques capable of progressively higher resolution split ultimately what appeared at lower resolution to be a single peak into two discrete peaks of JHE activity (pI 5.5 and 5.3). Neither peak was a degradation artifact of the other caused by conditions of IEF.
In rats, phosphorus deficiency (P-) has been shown previously to stimulate the linear bone apposition rate (BAR) and this P- effect is dependent on adequate intake of vitamin D. To investigate further the relative importance of the vitamin D3 metabolites, 1,25(OH)2D3, 24,25(OH)2D3, and 25(OH)D3, in BAR stimulation, we studied, in P- rats, the relationships between BAR and plasma levels of these three vitamin D3 metabolites following vitamin D3 deprivation. Three groups of rats were placed on diets differing only in phosphorus (P) and vitamin D3(D3) content, with one group diet deficient in both P and D3, one diet, P-, D3 replete, and one diet both P and D3 replete. Plasma levels of the three vitamin D3 metabolites, plasma Ca and P, isotopic Ca absorption and BAR measurements were carried out at 1, 3, and 5 weeks after onset of the test diets. In P-, D3 replete rats, both plasma levels of 1,25(OH)2D3 and BAR were increased throughout the 1 to 5 week study period, while 25(OH)D3 and 24,25(OH)2D3 levels were not significantly different from P and D3 replete controls. In P-, D3 restricted rats, BAR was decreased by one week, prior to any reduction in plasma levels of 25(OH)D3 and 24,25(OH)2D3 and while plasma 1,25(OH)2D3 levels were still well above control values. In this P- rat model, the vitamin D dependent BAR stimulation does not appear to be directly related to alterations in the plasma levels of 1,25(OH)2D3, 24,25(OH)2D3, or 25(OH)D3.
Kinetic analysis was performed on the juvenile hormone (JH) esterase activity in the hemolymph of feeding, last instar larvae of Trichoplusia ni (Lepidoptera: Noctuidae). When the results were analyzed by several different graphical and regression procedures, all approaches yielded the same conclusion that at least two forms of JH esterase active sites exist in the hemolymph. The apparent Km for one site for JH I, II and III was 8.5 X 10(-8) M, and 6.6 X 10(-8) M, respectively. The Km for the other site for JH I, II and III was 6.6 X 10(-7) M, 7.6 X 10(-7) M, 40 X 10(-7) M, respectively. When hemolymph JHE activity was subjected to high resolution isoelectric focusing (IEF), two distinct large peaks of JHE activity were observed, with pIs of 5.3 and 5.5, as well as a small peak at pI 5.1. Separate kinetic analysis of the JHE activity in each peak showed that only the higher Km active site for each substrate was present (in the 10(-7) M range). These data necessitate a change in the current model for JHE in T. ni, and some other insects, which states that a single active site is responsible for most or all of the JH esterase activity in vivo. The data also explain the different estimates of the Km of JHE in T. ni obtained by different laboratories. Studies on the purification of, and the development of inhibitors for, JHE esterase must consider the role of both JHE forms and sites in regulation of T. ni metamorphosis.
The present study has used a number of electrophoretic approaches to analyze the proteins in normal Trichoplusia ni larvae and those pseudoparasitized by Chelonus spp. A number of feeding-stage, hemolymph proteins appear or increase dramatically only during the final larval stadium. Other proteins highly abundant only during the penultimate stadium disappear or decrease dramatically during the final stadium. The comparative protein profiles of penultimate instar, pseudoparasitized larvae are very similar to those of last instar larvae. These changes in hemolymph proteins are seen on gels resulting from electrophoresis, isoelectric focusing (wide range and narrow range Ampholine and very narrow range Immobiline gels) and SDS-disc electrophoresis. It is concluded that the entire last instar developmental pattern of protein gene products is occurring precociously in pseudoparasitized larvae.
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The linear rate of bone mineral apposition (BMAR) was measured in vitamin D-deficient and vitamin D-sufficient adult rats before and during treatment with either 25-hydroxyvitamin D3 (25OHD3), 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], or 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3]. Dietary vitamin D restriction caused a fall in BMAR which began after 1 week and fell progressively to a value of 35-50% of control values by 4 weeks. The fall in BMAR was related to a fall in the serum concentrations of 25(OH)D3 and 24,25-(OH)2D3, without a fall in the 1,25-(OH)2D3 concentration. Dietary supplementation of the D-deficient animals with either 25OHD3 or 24,25-(OH)2D3 at doses of 200 ng/day restored BMAR. If vitamin D-deficient animals were thyroparathyroid-ectomized before supplementation with vitamin D metabolites, 24,25-(OH)2D3 administration was without effect on BMAR. The combined administration of PTH and 24,25-(OH)2D3 to such animals led to a restoration of the BMAR to normal. In vitamin D-sufficient animals, parathyroidectomy led to a 50% reduction in BMAR, which could be restored by treatment with PTH alone but not with 24,25-(OH)2D3. Simultaneous treatment of these animals with PTH and 24,25-(OH)2D3 led to a greater than normal increase in BMAR (130% of control) in these animals. These data support the concept that 24,25-(OH)2D3 has a role in the regulation of bone formation and/or mineralization, and demonstrate the interrelation between the effects of PTH and 24,25-(OH)2D3 on bone.
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