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Biomedical subjects

D C Moore

Publications and source records attributed to D C Moore.

At least 19 recordsLinked to original sources

Inhibition by 1,25 dihydroxyvitamin D3 of c-myc down-regulation and DNA fragmentation in cytosine arabinoside-induced erythroid differentiation of K562 cells.

The effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on DNA fragmentation, altered expression of the heat shock protein (hsp) 70 gene, and protooncogenes c-myc and c-myb was studied during chemical induction of erythroid differentiation in K562 cells. Preincubation of K562 cells with 1,25(OH)2D3 did not alter the concentration of hemoglobin in cells which did differentiate, but led to a reduction in the accumulation of low molecular weight DNA generated by Ara-C administration. The extent of this reduction was similar to the degree of inhibition of hemoglobin formation in the culture as the whole. Preincubation with 1,25(OH)2D3 had no effect on the increase of hsp 70 gene expression induced by a 48-hr treatment with Ara-C, but prevented the Ara-C-induced down-regulation of the protooncogene c-myc. The protooncogene c-myb was down-regulated after 15 min of treatment with Ara-C, and exposure to 1,25(OH)2D3 prior to Ara-C caused a further down-regulation of its expression. The data suggest that the events associated with erythroid differentiation may be separable into at least two groups; one of these may have an influence on the kinetics of the cell cycle traverse, and the other may be related to the expression of the erythroid phenotype.

Blotting, Northern

Inhibition by 1,25 dihydroxyvitamin D3 of chemically induced erythroid differentiation of K562 leukemia cells.

The physiologically active form of vitamin D, 1,25 dihydroxyvitamin D3 [1,25(OH)2D3], was found to inhibit erythroid differentiation of human leukemic K562 cells. Differentiation was induced by 1 mumol/L arabinocytosine (Ara-C), 40 mumol/L tiazofurin, 1 mumol/L aphidicolin, or 1 mumol/L hydroxyurea, and was monitored daily by the appearance of hemoglobin in an increasing proportion of cells. Pretreatment for 48 hours with 2.4 x 10(-8) mol/L 1,25(OH)2D3, a concentration that is also optimal for induction of monocytic differentiation of HL-60 cells, reproducibly inhibited subsequent induction of erythroid differentiation by all of the above inducers, and modified the morphologic changes that Ara-C produced in these cells. The inhibition of hemoglobinization was approximately 50% irrespective of the degree of differentiation produced by the various inducers, but growth inhibition associated with exposure to the inducers was not affected by 1,25(OH)2D3. Similar inhibition of differentiation by 1,25(OH)2D3 was observed in mouse erythroleukemia cells MEL-D1B treated with 5 mmol/L hexamethylenebisacetamide. The inhibitory effect of 1,25(OH)2D3 on erythroid differentiation of K562 cells was abrogated by cyclohexamide (20 micrograms/mL), an inhibitor of protein synthesis. The mRNA for 1,25(OH)2D3 receptor (VDR) was detected in K562 cells, and was downregulated by a 96-hour exposure to 1,25(OH)2D3 or a 48-hour exposure to Ara-C. The presence of VDR mRNA suggests a physiologic role for 1,25(OH)2D3 in K562 cells that are precursors of erythroid cells. This role is perhaps to shift the pathways of differentiation from the erythroid to the monocytic lineage.

Animals

Association of c-myc protein with enzymes of DNA replication in high molecular weight fractions from mammalian cells.

Oncoprotein c-myc is expressed in proliferating but not quiescent mammalian cells, and its overexpression or inappropriate expression is associated with malignant transformation. However, in spite of an intense interest, the normal function of this protein has remained elusive. As a step towards the elucidation of the function of c-myc protein, we studied its distribution within several types of cells, including HL 60, K 562, COLO 320, and CHEF/18 cells. In all of the cells studied, c-myc protein was detected in high molecular weight protein fractions, in 350-600 Kd range, in gel-exclusion chromatography and sucrose gradient centrifugation. This distribution of c-myc protein coincided with the distribution of DNA polymerase alpha and several other enzymes necessary for DNA replication. The data suggest that c-myc product may be a component of the replitase complex of enzymes involved in nuclear DNA replication.

Animals

Vitamin D analogs inhibit erythroid differentiation and induce monocytic differentiation of leukemic cells with the same relative potency.

Myeloid leukemia cells of human and murine origin can be induced to differentiate into more mature forms which lose their neoplastic properties. The hormonal form of vitamin D is a powerful inducer of monocytic differentiation, but its therapeutic use is limited by hypercalcemia. It was recently reported that a novel derivative of vitamin D, 1,25-dihydroxy-16-ene-23-yne-vitamin D3, is an exceptionally potent inducer of monocytic differentiation, and prolongs survival of mice bearing leukemia cells. We now show that this compound is also a most potent inhibitor of erythrodifferentiation. This finding has important implications for the control of hematopoiesis.

Calcitriol

Autogeneic bone marrow and porous biphasic calcium phosphate ceramic for segmental bone defects in the canine ulna.

The purpose of this study was to evaluate a porous biphasic hydroxyapatite-calcium phosphate ceramic as a modifier and extender of an autogeneic marrow graft for filling a 2.5-cm segmental bony defect. Twenty adult mongrel dogs were surgically treated to create diaphyseal defects in the left ulnae. The defects were (1) filled with autogeneic bone marrow mixed with granular hydroxyapatite-tricalcium phosphate ceramic (granular ceramic); (2) grafted with a solid block of ceramic soaked in autogeneic bone marrow (block ceramic); (3) received no graft (no implant); or (4) were grafted with autogeneic bone marrow alone (bone marrow). All animals were followed clinically and roentgenographically for 24 weeks and then killed. Repair of diaphyseal defects with the block ceramic led to three solid unions and three fibrous unions; with the granular ceramic implants and marrow, the defects of five dogs formed solid unions, and one progressed to a fibrous union. Defects in all five dogs grafted with autogeneic bone marrow united. The three dogs with no implant formed nonunions. Histology showed normal marrow and only a light immune reaction. Complete bridging of the defect in the dogs treated with the granular ceramic occurred significantly earlier than bridging in the dogs grafted with bone marrow alone. Histomorphometry, performed on the block ceramic implants indicated active resorption of ceramic. Clinically, addition of ceramic to a marrow graft improved the handling characteristics of the graft material and accelerated healing according to roentgenographic evaluation.

Animals

Body image and eating behavior in adolescent boys.

A questionnaire about attitudes toward body weight and shape, and eating and weight control practices, was administered to 895 adolescent boys. Overall, 42% were dissatisfied with their weight and 33% with their body shape. Sixty-eight percent of the dissatisfied normal weight boys thought they were underweight and 32% thought they were overweight. Subjects dissatisfied with their body shape were most likely to desire an increased chest and arm size and decreased abdomen size. Binge eating (24%) and fasting (12%) were the most prevalent eating practices and were more common in boys dissatisfied with weight or shape. There was no difference in prevalence of eating practices between boys wishing to gain and boys wishing to lose weight. Although many boys were concerned about body weight and shape, they wished to increase weight and muscularity, rather than lose weight. Binge eating was common, but was not related to the binge-purge cycle described in girls, because losing weight is not a major concern, and other weight control practices were not more common among boys who wanted to lose weight vs gain.

Adolescent

Predictors of improvement in tardive dyskinesia following discontinuation of neuroleptic medication.

Forty-nine chronic psychiatric out-patients (ten were schizophrenic) with tardive dyskinesia (TD) were examined monthly for a mean of 40 weeks (range 1-59 months) after discontinuation of neuroleptic medication. Complete and persistent reversibility of TD was rare (2%), but many patients showed noticeable improvement in movements within the first year of discontinuation, which was sometimes interrupted by psychological relapse. Using three separate outcome measures and appropriate model-fitting techniques for each, we identified several predictors of improvement in TD, including an affective or schizoaffective psychiatric diagnosis, chronic (over 20 years) psychiatric illness, being employed, younger age, and increased neuroleptic dose before discontinuation. Consistent findings emerging from these analyses suggest that the type and history of psychiatric illness affect the course of TD.

Adult

Morphological and physiological effects of beta-hydroxybutyrate on rat embryos grown in vitro at different stages.

Diabetic women are more likely to give birth to infants with congenital malformations than are nondiabetic women. Rodent embryos have been used as a model for the study of abnormal fetal development associated with maternal diabetes, and some of the metabolic factors which are altered in diabetes, such as raised glucose and ketones, have been shown to cause abnormal development of rodent embryos in vitro. The present work explores further the teratogenicity of beta-hydroxybutyrate to rat embryos. To determine the sensitivities of rat embryos at different stages of their development, rat embryos at 9.5 days of gestation have been cultured in vitro for 24 or 48 h, with or without 4 x 10(-2) M beta-hydroxybutyrate for all or part of the culture period. The embryos have been examined by scanning electron microscopy, and a detailed morphometric analysis of one tissue, the neuroepithelium, has been undertaken. The results confirm that beta-hydroxybutyrate causes abnormal development of rat embryos. The results of experiments in which embryos were exposed to beta-hydroxybutyrate for only part of a 48 h culture show that embryos exposed to beta-hydroxybutyrate for a complete 48 h culture are more severely affected than embryos exposed to beta-hydroxybutyrate for only part of the culture and that embryos are more vulnerable to beta-hydroxybutyrate during the first half of a 48 h culture (equivalent to 9.5 to 10.5 days of gestation) than during the second half of a 48 h culture (10.5 to 11.5 days of gestation). The results of experiments in which embryos were cultured with beta-hydroxybutyrate from 9.5 days of gestation for 24 h (equivalent to 9.5 to 10.5 days of gestation) showed that some effects of beta-hydroxybutyrate are already apparent after 24 hours in culture. Many of the abnormalities produced by beta-hydroxybutyrate can be classified as embryonic retardations rather than malformations--that is, embryos show features characteristic of normal, but younger, embryos. Embryos exposed to beta-hydroxybutyrate for the complete 48 h culture period consume less glucose and produce less lactate than control embryos on a per embryo basis, but not on a per microgram protein basis, suggesting that the reduced metabolism is an effect of beta-hydroxybutyrate-induced developmental delay rather than a cause of it.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Hydroxybutyric Acid

Serum cortisol responses in febrile children.

Adrenocortical stress response in children with a variety of febrile illnesses was prospectively evaluated in 76 patients presenting to a general pediatric clinic with temperature greater than 101 degrees F (38.3 degrees C). Serum cortisol concentrations at presentation and again after recovery from infection were determined. Overall mean magnitude change in cortisol concentrations was 3.6-fold. Cortisol response was unrelated to the height of temperature but significant differences depending on clinical diagnosis were identified. The largest response (5-fold) was observed in patients with pneumonia, bacterial meningitis and fever of undetermined etiology. Current recommendations to double or triple replacement hydrocortisone dosage during times of increased stress in children with adrenal insufficiency are adequate only for simple febrile illnesses such as upper respiratory infection and streptococcal pharyngitis but could be subtherapeutic for infections such as pneumonia, meningitis and fever of undetermined origin, which imply a greater systemic involvement. It is possible, but untested, that a 4- to 5-fold increase in dosage would be more appropriate in those conditions.

Adrenal Cortex

Intralenticular abscess.

Intralenticular abscess is an uncommon complication of surgery or trauma. A case of intralenticular abscess following penetrating trauma is presented. In this case, the offending organism was identified as Propionibacterium acnes. This organism is considered to be a cause of slowly progressing endophthalmitis and has been implicated as a cause of the so-called toxic lens syndrome.

Abscess

Body image and eating behavior in adolescent girls.

To determine attitudes toward body weight and shape and eating and weight control practices among adolescent girls, an anonymous questionnaire was administered to 854 adolescent girls and young women aged 12 through 23 years who were seen in a military adolescent outpatient clinic. Overall, 67% were dissatisfied with their weight, and 54% were dissatisfied with their body shape. Dissatisfaction with weight and shape varied positively with increasing body weight but not with increasing age. Binge eating had occurred in 30.4%, and weight control behavior, such as dieting, fasting, vomiting, and stimulant, laxative, and diuretic use, had occurred in 38.2%, 30.7%, 8.5%, 9.5%, 3.3%, and 6.2%, respectively, varying positively with increasing weight. Thirty-six percent of those adolescent girls who saw themselves as overweight desired an inappropriate weight loss, and 61% of these, who desired an excessive loss, exhibited an increased prevalence of weight control behaviors and were less likely to believe that they had an eating problem. Dissatisfaction with body weight and shape, and eating behaviors, such as dieting, binge eating, fasting, and vomiting, are common in adolescent girls, many of whom are attempting weight control without an accurate perception of what is normal.

Adolescent

Prenatal sonographic diagnosis of Pena-Shokeir syndrome type I, or fetal akinesia deformation sequence.

We report on a familial case of Pena-Shokeir syndrome type I (fetal akinesia deformation sequence) born to healthy parents. The antenatal ultrasound diagnosis was based on hydramnios, restricted limb movements, decreased fetal chest movements, small chest, arthrogryposis, clubfoot, fixed extension of knees, fixed flexion of elbows, camptodactyly, kyphosis of thoracic spine, cryptorchidism, and small muscle bulk. Thymic hyperplasia was noted at autopsy.

Abnormalities, Multiple