Involvement of Cellular Retinoic Acid (CRABP) or Retinol (CRBP) Binding Proteins and 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) receptors in the response of cultured cells to retinoic acid and 1,25(OH)₂D₃ was examined. A new method for saturation analysis of CRABP and CRBP was applied to human tumors, human neuroblastoma cells, which retinoic acid causes to differentiate, and a bioselected subline resistant to retinoic acid. These data suggest that CRABP may not mediate cell differentiation by retinoic acid. In other studies, 1,25(OH)₂D₃ receptors and bioresponses were characterized in cultured primate cells. Rhesus monkey kidney cells (LLC-MK₂) were resistant to 1,25(OH)₂D₃-dependent induction of 25(OH)D-24-hydroxylase enzyme. The ED₅₀ in LLC-MK₂ cells was 10-100 fold higher than in other cultured cells. This resistance resulted from a low affinity receptor. Since the LLC-MK₂ variant receptor did not differ in size from the wild type rhesus 1,25(OH)₂D₃ receptor, (Mᵣ = 52 kDa) a subtle alteration in the receptor likely caused the decreased ligand affinity. Also of interest was the possible cellular resistance to 1,25(OH)₂D₃, in the owl monkey (Aotus trivurgatus), which generally occurs in new world primates. Owl monkey kidney (OMK) cells had the same content of receptors for 1,25(OH)₂D₃ and sensitivity to this hormone as cells from the rhesus monkey (old world primate). The ED₅₀ for induction of 24hydroxylase was 2-3 nM in both the OMK cells and the rhesus monkey fibroblasts. Both cells contained 2300 high affinity receptor molecules per cell, which bound DNA and were characterized by immunoblot as 52 kDa proteins. 1,25(OH)₂D₃ treatment increased the content of 1,25(OH)₂D₃ receptors in OMK cells, by increasing the synthesis of receptor mRNA. These data indicate the owl monkey is not resistant to 1,25(OH)₂D₃, unlike other new world primates. This finding was confirmed independently by demonstration that the owl monkey maintained mean serum 1,25(OH)₂D₃ levels (29 pg/ml) in the range of old world primates (33 pg/ml) and humans, in contrast to the elevated 1,25(OH)₂D₃ in other new world primates (97-129 pg/ml). This result suggests the alteration of 1,25(OH)₂D₃-endocrine dynamics in new world primates occurred subsequent to the evolutionary divergence of the owl monkey.

Papua New Guinea has been classified by the World Health Organisation as an area where clinical vitamin A deficiency (VAD) exists. This is at variance with the experience of the local physicians who do not encounter classical VAD in clinical practice. This pilot study was carried out to resolve this contradiction, since many suggestions have been made to fortify foods with Vitamin A. If done in the absence of concrete data to back up this classification, it could take the focus away from the real problem as well as potentially create problems of Vitamin A toxicity. Therefore, answers from this study could have far reaching implications in a country such as PNG, which has high childhood mortality and limited financial and manpower resources. The objective of this study was to determine the vitamin A status and identify risk factors of VAD in children aged 6 months to 6 years in a rural area of Papua New Guinea. The survey was carried out in the Ramu region of Madang province. Households and children were randomly selected and standard questionnaires were used to collect information about diet, previous illnesses and night blindness. The weight and height of all children was recorded and an ocular and physical examination carried out by trained personnel. In addition, haemoglobin estimation and examination of blood films for malaria parasites was carried out in all the children. In a randomly selected number of children, estimations of serum retinol and other micronutrient levels were carried out. Results: A total of 609 children were enrolled in the study. Biochemical parameters were studied in 106 of them .The mean age of the children was 35 months. Possible night blindness was reported in 4 children. No xerophthalmia was seen. The prevalence of serum retinol levels ( 0.7 (mol/L (WHO suggested cut off values for subclinical VAD) was 10.3%. Anthropometric indicators indicated a high proportion of the children had stunting and wasting or both. Analysis of dietary patterns, maternal literacy, food availability and other surrogate indicators indicated that the population is at mild-moderate risk of developing VAD. In conclusion, no evidence of clinical vitamin A deficiency was found. Subclinical vitamin A deficiency seemed to occur in this population at a level of mild-moderate public health importance. Further studies need to be carried out to assess the situation in different areas in PNG before policy decisions can be made with regards to mass vitamin A supplementation.

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Graduation date: 1991

Graduation date: 1931

Graduation date: 1940

Graduation date: 1946

Graduation date: 1931