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H S Ahn

Publications and source records attributed to H S Ahn.

14 recordsLinked to original sources
PubMed2026

Genomic basis of developmental defects of enamel and sex-specific effects.

We conducted a multi-ancestry genome-wide association study (GWAS) of developmental defects of enamel (DDE) in the primary dentition among 6,061 U.S. preschool-aged children (3-5 years). We investigated four DDE phenotypes (demarcated opacities, diffuse opacities, hypoplastic defects, and a combined DDE trait) leveraging main-effect models, joint gene-sex interaction testing (2df), and sex-stratified analyses. SNP-based heritability for the combined DDE trait was estimated at 20%, with concordance analyses robustly supporting a genetic etiology. We identified 39 unique genome-wide significant loci (P<5&#xd7;10 ), with five surpassing a study-wide Bonferroni-corrected statistical significance criterion (P<1.25&#xd7;10 9), including Y RNA and ALDH1A1. The main-effect GWAS identified 20 loci, including HBS1L and MYB, genes regulating hematopoiesis with plausible roles in amelogenesis. Joint test and sex-stratified analyses revealed 19 additional loci, including ALDH1A1, TENM2, and DLGAP2, demonstrating sex-specific heterogeneity. Nineteen loci exhibited sex-specific differences after Bonferroni correction (P<2x10-3), including genes involved in retinoic acid signaling (ALDH1A1), odontogenesis (TENM2), and neurodevelopment (DLGAP2, CDH10). Pathway enrichment highlighted ectodermal and synapse organization networks, suggesting shared etiological mechanisms between DDE and systemic conditions like neurofibromatosis and autism spectrum disorder. Notably, no locus generalized in an external GWAS of permanent dentition DDE, underscoring fundamental biological differences in the genetic architectures governing primary versus permanent enamel formation. Crucially, a comprehensive cross-trait pleiotropy lookup against early childhood caries (ECC) revealed no shared genetic architecture, supporting the notion that the established clinical and epidemiological association between DDE and ECC is likely driven by structural defects increasing caries lesion susceptibility rather than genetic pleiotropy. By integrating gene-sex interaction testing, this study offers novel insights into the complex, sexually dimorphic genetic etiology of DDE and augments the biological evidence base that can support the development of precision pediatric dentistry.

developmental defects of enamel↗
PubMed1979

Interaction of LSD and other hallucinogens with dopamine-sensitive adenylate cyclase in primate brain: regional differences.

The influence of D-lysergic acid diethylamide (LSD) and mescaline on adenylate cyclase activity was studied in homogenates of Cebus and rhesus monkey anterior limbic cortex (ALC), frontal cortex (FC), caudate nucleus and retina. Previous studies have shown these tissues to contain dopamine-stimulated adenylate cyclase (AC). In addition, we are now reporting the presence of a dopamine-sensitive adenylate cyclase in the auditory cortex. AC of ALC and auditory cortex was stimulated by LSD and mescaline, whereas activity of FC, caudate nucleus and retina was not stimulated by the same agents. In contrast to regional specificity for stimulation, LSD was capable of antagonizing dopamine-stimulated activity in all brain regions examined. LSD and mescaline produced similar maximal stimulation (about 70%) of AC of ALC homogenates, but the EC50 for LSD (0.43 micrometer) was about one-tenth that for mescaline (4.5 micrometer). Similar relative potencies were also observed for the auditory cortex enzyme. Although much weaker than LSD, methamphetamine also produced a dose-dependent stimulation of ALC AC. Both agonist and antagonist effects of the hallucinogens appear to involve interaction with dopamine receptors; LSD- or methamphetamine-stimulated activity in ALC was blocked by haloperidol and fluphenazine, which are dopamine antagonists, but not by phentolamine, an alpha-receptor blocker. Antagonism of dopamine by LSD in both ALC and FC was found to be competitive and mescaline was an effective but weaker antagonist than was LSD. In addition, neither histamine--nor Gpp(NH)p--stimulated activity of FC was inhibited by LSD. It is proposed that the occurrence of dopamine agonistic action of hallucinogens in only certain regions of primate brain may provide a basis for at least some of the behavioral effects of LSD, mescaline and methamphetamine in primates.

Adenylyl Cyclases↗
PubMed1979

Anterior pituitary adenylate cyclase: stimulation by dopamine and other monoamines.

Adenylate cyclase activity of homogenates of anterior pituitary from rat, rabbit and monkey was stimulated by dopamine, other amine neurotransmitters and Gpp(NH)p. The concentration of dopamine for half-maximal stimulation of activity was 2--5 micrometer. Studies with selective agonists and antagonists indicated the presence of dopamine receptors and beta-adrenergic receptors coupled to adenylate cyclase in anterior pituitary. In addition, histamine stimulated activity in rabbit and monkey, but not in rat, anterior pituitary.

Adenylyl Cyclases↗
PubMed1979

Aging and monoamine receptors in brain.

Biochemical evidence is presented for selective decreases in biogenic amine receptor systems with age in the rabbit. Dopamine-stimulated adenylate cyclase activity in striatum, hypothalamus, frontal cortex, and anterior limbic cortex declined by about 50% as rabbits aged from less than 1 to 5 years of age. Similar decreases were found for histamine-stimulated activity in hypothalamus and the cortical regions. These changes were in maximal response rather than in affinity for amine. In contrast, dopamine-stimulated adenylate cyclase of retina and both basal and Gpp(NH)p-stimulated activity in these regions were not altered with age. In addition, with age the number of binding sites for [3H]spiroperidol, a dopamine antagonist, decreased by 30--40% without change in ligand affinity in striatum and limbic cortex. These changes in striatum and cortex occurred in the absence of decreases in either dopamine concentration or choline acetylase activity. It is proposed that selective age-dependent decreases in the functional number of biogenic amine receptors occur in the absence of, or independent from neuronal cell loss, possibly by a mechanism of desensitization. These changes occurred in brain regions that in man are thought to be of importance in the age-related loss of cerebral function.

Adenylyl Cyclases↗
PubMed1978

Biogenic amine-stimulated adenylate cyclase and spiroperidol-binding sites in rabbit brain: evidence for selective loss of receptors with aging.

Evidence for selective decreases in biogenic amine receptor function with age in the rabbit has been obtained. Dopamine-stimulated adenylate cyclase activity in the striatum (caudate-putamen) of rabbit brain declined by about 50 percent as rabbits aged from less than 1 to 4 to 5 years of age. Similar decreases in transmitter-stimulated adenylate cyclase activity were found for histamine as well as for dopamine and norepinephrine in hypothalamus, frontal cortex and anterior limbic cortex. Isoproterenol-stimulated activity was also decreased with age in frontal cortex. These changes appeared to represent decreases in maximal response and not alteration in affinity for amine. In contrast, dopamine-stimulated adenylate cyclase of retina and transmitter-independent (basal or Gpp(NH)p-stimulated) activity in each of the regions studied were not altered with age. Dopamine receptors in striatum directly assessed by measurement of [3H]-spiroperidol binding revealed a comparable decrease in the number of binding sites without change in ligand affinity. Preliminary data also indicated decreased spiroperidol binding sites in the cortical regions of older animals. These changes in striatum and cortex were evident in the absence of decreases in either dopamine content or choline acetylase activity, an activity presumed to be present in neurons containing dopamine receptors. It is proposed that selective age-dependent decreases in postsynaptic biogenic amine receptor content occur in the absence of, or independent from, neuronal cell loss, possibly by a mechanism involving receptor desensitization. These changes occur in the animal model in those brain regions which in man are thought to be of importance in the loss of cerebral function that is found with senscence.

Adenylyl Cyclases↗
PubMed1976

Catecholamine-sensitive adenylate cyclase in frontal cortex of primate brain.

Adenylate cyclase activity (AC) of homogenates of monkey frontal cortex was stimulated by catecholamines (dopamine, norepinephrine and isoproterenol), apomorphine, clonidine, NaF and GPP(NH)P. The increment in activity due to dopamine was enhanced in the presence of GPP(NH)P. The AC was also stimulated by 0.2-0.4 mM Ca2+ in the presence of 0.2 mM EGTA; at 0.8 mM Ca2+ had little or no influence on basal or NaF-stimulated activity. However, as Ca2+ concentration was increased from 0.2 to 0.8 mM stimulation by dopamine or GPP(NH)P was progressively inhibited. These results suggest a possible function of Ca2+ in modulating neurotransmitter stimulation of AC in the monkey frontal cortex. The AC exhibited higher sensitivity to dopamine than to norepinephrine or isoproterenol; however dopamine and norepinephrine caused the same maximum stimulation of the enzyme, a stimulation womewhat greater than that produced by isoproterenol. An additivity in stimulating AC was observed for dopamine and isoproterenol but not for dopamine and norepinephrine. Norepinephrine- or dopamine-stimulated AC was effectively blocked by fluphenazine and other dopamine-receptor blocking agents (relative potency for blockade; fluphenazine, haloperidol greater than clozapine, thioridazine greater than pimozide) but not by propranolol, a beta-receptor blocker. In contrast, isoproterenol-stimulated AC was antagonized by propranolol or alprenolol but not by fluphenazine. On the basis of these results, at least two distinct receptors appear to be associated with AC of monkey frontal cortex: (1) a beta-receptor stimulated by isoproterenol and (2) a new type of dopamine or dopamine-norepinephrine receptor, stimulated by either dopamine or norepinephrine. This latter system differs from more typical dopamine receptors found in caudate, retina and limbic cortex in that (a) it is not stimulated by 1-(3,4-dihydroxybenzyl)-4-(2-pyrimidinyl) piperazine (S584); (b) it is stimulated significantly by the putative alpha-receptor agonist, clonidine; (c) it is more sensitive to blockade by clozapine than primate retina or caudate; also the sensitivity to haloperidol is greater than has been reported for non-primate caudate; (d) it is very sensitive to stimulation by norepinephrine and to blockade by phentolamine (an alpha-receptor blocker).

Adenylyl Cyclases↗