Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psychometric deviance in personality traits as assessed by the Minnesota Multiphasic Personality Inventory (MMPI; Dahlstrom, Welsh, & Dahlstrom, 1982) was compared between adopted-away, high-risk (HR) offspring of schizophrenic biologic mothers and low-risk (LR) controls. A subsample of the Finnish Adoptive Family Study (Tienari et al., 2000) included 60 HR adoptees and 76 LR control adoptees who were tested by the MMPI before the onset of any psychiatric disorder at the mean age of 24 years. The HR group was found to be distinguishable based on deviant scores on the scales HOS and HYP, indicating emotional unresponsiveness, restricted affectivity, and decreased energy. These may also be considered possible premorbid and prodromal signs of future schizophrenia among the HR adoptees.
 ...
PMID:Psychometric deviance measured by MMPI in adoptees at high risk for schizophrenia and their adoptive controls. 1527 92

1alpha,25-Dihydroxyvitamin D(3) (1) regulates a variety of biological actions through vitamin D receptor (VDR), including calcium and phosphorus homeostasis, bone remodeling, cellular proliferation and differentiation and many other functions. To enhance its potency and to study the structure/function relationship, we synthesized a series of analogs of 1 with a modification at the C-2alpha position. Introducing 2alpha-methyl, 2alpha-(3-hydroxypropyl), or 2alpha-(3-hydroxypropoxy) group increased its binding affinity for the VDR 2- to 4-fold compared to 1. The crystal structures of the VDR bound to these analogs provide a molecular explanation for the interaction between the 2alpha-substituents and water molecules exist in the VDR-ligand binding domain. Based on the accumulated knowledge in VDR agonists, we synthesized 2-substituted analogs of 'double side chain' (gemini), 19-norvitamin D(3) (MART-10), TEI-9647 (VDR antagonist), 1-alkylated vitamin D(3), 14-epi-previtamin D(3) etc. Gemini analogs showed potent HL-60 cell differentiation activity (13-38 times compared to 1), and MART-10 exhibited remarkable antiproliferative activity on PZ-HPV-7 cells even at 10(-10) M. (24S)-2alpha-(3-Hydroxypropoxy)-24-propyl-TEI-9647 showed potent VDR antagonism, and its IC(50) value was 7.4 pM against 10 nM of 1. 1alpha-Methyl-2alpha-(3-hydroxypropyl)-25-hydroxyvitamin D(3) improved the binding affinity for the mutant VDR(Arg274Leu), which causes hereditary vitamin D resistant rickets. 1alpha,25-Dihydroxy-2alpha-methyl-14-epi-previtamin D(3) showed moderate osteocalcin transcriptional activity on HOS cells. We theorize that modification at A-ring alone and in combination with functionalization of the other parts of the vitamin D molecule would provide important new information on the mechanism of vitamin D actions that could lead to the development of new therapeutic regimes for the treatment of various diseases.
 ...
PMID:Structural refinement of seco-steroidal skeleton and the biological activity through nuclear receptors. 1875 37