Genetic epidemiology of tooth agenesis in Japan: a population- and family-based study.

Tooth agenesis is one of the most common congenital anomalies in humans. However, the etiology of tooth agenesis remains largely unclear, as well as evidence base useful for genetic counseling. Therefore, we estimated the prevalence and sibling recurrence risk, and investigated agenetic patterns systematically. Tooth agenesis was classified into two subtypes: hypodontia (one to five missing teeth) and oligodontia (six or more missing teeth). The prevalence of these two subtypes were 6.8% [95% confidence interval (CI): 6.1-7.7%] and 0.1% (95% CI: 0.04-0.3%), respectively, and sibling recurrence risk of these were 24.5% (95% CI: 13.8-38.3%) and 43.8% (95% CI: 26.4-62.3%), respectively. This result suggests that the severe phenotype, oligodontia, might be mostly transmitted in a dominant fashion. Using a simple statistical modeling approach, our data were found to be consistent with a bilateral symmetry model, meaning that there was equal probability of missing teeth from the right and left sides.

Possible involvement of nitric oxide in carbachol-induced activation of transglutaminase in rat superior cervical sympathetic ganglia.

The addition of a muscarinic agonist, carbachol (Carb, 0.1 mM), to a physiological medium markedly increased Ca(2+)-dependent transglutaminase (TG) activity (approximately 10-fold) in isolated rat superior cervical sympathetic ganglia (SCG) following in vitro aerobic incubation for 30 min at 37 degrees C. The Carb-evoked stimulation of ganglionic TG activity was considerably reduced (-51%) in the presence of NG-monomethyl-L-arginine (L-NMMA, 50 microM), a selective inhibitor of nitric oxide (NO) synthase. While the suppressant effect of L-NMMA was completely eliminated by the addition of an excess concentration of L-arginine (0.5 mM), a precursor of NO. These observations imply that Carb-induced TG activation possibly involves NO mediation in SCG tissue. The Carb-induced elevation in ganglionic TG activity was markedly reduced (-84%) at as early as 15 min of incubation in the medium containing hemoglobin (Hb) (20 microM), an agent that scavenges only extracellular NO gas. Thus, it is evident that a large fraction of NO released from inside the neuronal cells to extracellular space could rapidly diffuse back into the same group of cells to induce activation of the tissue TG. Methylene blue (MB), an inhibitor of soluble guanylate cyclase (GC), at 0.5 mM, a concentration which is effective in almost abolishing the Carb-evoked synthesis of cyclic GMP (cGMP), had no effect on ganglionic TG activation induced by Carb. Therefore, an increase in cGMP synthesis mediated by NO might not participate in NO-dependent ganglionic TG activation following the stimulation with Carb.(ABSTRACT TRUNCATED AT 250 WORDS)

The intercellular communication via nitric oxide and its regulation in coupling of cyclic GMP synthesis upon stimulation of muscarinic cholinergic receptors in rat superior cervical sympathetic ganglia.

Cyclic GMP (cGMP) production in rat superior cervical sympathetic ganglia (SCG) was markedly increased (ca. 7-9-fold) by the addition of either acetylcholine (ACh; 0.1 mM) or a muscarinic agonist, carbachol (Carb; 0.1 mM), in the presence of an inhibitor (3-isobutyl-1-methylxanthine) for cGMP hydrolytic enzyme during in vitro aerobic incubation at 37 degrees C for 5 min. The ACh-induced accumulation of cGMP in SCG was effectively blocked (-73%) by the further addition of atropine (10 microM), a muscarinic antagonist, whereas a nicotinic blocker, hexamethonium (10 microM) partially antagonized (-41%) this ACh stimulation. The inhibitory effect of hexamethonium on ACh-evoked ganglionic cGMP production was effectively augmented (-83%) by addition of NG-monomethyl-L-arginine (L-NMMA, 50 microM), a compound that inhibits nitric oxide (NO) synthesis from L-arginine. Comparable inhibition of cGMP formation was observed following application of L-NMMA to the SCG upon stimulation of Carb. In contrast, L-NMMA had no effect on the decreased level of ACh-evoked cGMP production caused by the muscarinic antagonist. The Carb-induced elevation of ganglionic cGMP synthesis was significantly reduced within 1 min of incubation in the medium containing hemoglobin (Hb; 20 microM), an agent that scavenges only the extracellular fraction of NO. Thereafter, the tissue cGMP formation attenuated to the control level by subsequent incubation for several minutes. Addition of protein kinase C (PKC) activator, 12-O-tetradecanoylphorbol 13-acetate (TPA; 1 microM) to the medium significantly decreased Carb-evoked cGMP synthesis (-61%) in SCG, whereas superoxide dismutase (SOD; 30 U/ml) only slightly suppressed the Carb stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Blockade effect of nerve growth factor on GM1 ganglioside-induced activation of transglutaminase in superior cervical sympathetic ganglia excised from adult rat.

The activity of transglutaminase (TG), a Ca(2+)-dependent enzyme indicating tissue degradation or differentiation, showed in isolated adult rat superior cervical ganglia (SCG) a rapid (within 15 to 30 min) and marked (approx. 5- to 8-fold) increase with the addition of either GM1 ganglioside (GM1, 5 nM), which is rich in synapses, or sialyl cholesterol (SC, 20 microM), a synthetic sialic acid-containing compound, to the incubation medium at 37 degrees C. Under the same incubation conditions, addition of GM1 or SC decreased protein kinase C (PKC) activity (-26% to -39%) in the cytosolic fraction of the SCG, but increased the enzymic activity (+39% to +61%) in the particulate (cell membrane) fraction, suggesting that a sialic acid-containing compound (GM1 or SC) promotes PKC translocation from the cytosol to the membrane in ganglionic neurons. By contrast, addition of a promoting factor for survival of sympathetic neurons even in adulthood, nerve growth factor, (NGF, 0.25 micrograms/ml) to the medium significantly decreased ganglionic TG activity (-43%). This inhibition was completely antagonized by the co-addition of NGF-monoclonal antibody (0.75 microgram/ml). An effective blockade of GM1- or SC-induced stimulation of ganglionic TG activity was seen by further addition of NGF to the medium. Also, NGF almost abolished the translocation of ganglionic PKC activity induced by the sialic acid-containing compounds, although either NGF or 12-O-tetradecanoylphorbol ester (TPA) alone stimulated the cytosolic PKC activity (approx. +30%) in the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of axotomy on nitric oxide-dependent cyclic GMP production of rat superior cervical sympathetic ganglia in response to norepinephrine.

Cyclic GMP (cGMP) production in superior cervical sympathetic ganglia (SCG) isolated from rats was markedly enhanced (approx. 4.5-fold) by the addition of L-arginine (L-Arg, 100 microM) plus an inhibitor (3-isobutyl-1-methylxanthine) for cGMP hydrolytic enzyme during in vitro aerobic incubation at 37 degrees C for 10 min. This accelerated accumulation of ganglionic cGMP was effectively reversed by approximately 50% when NG-monomethyl-L-arginine (L-NMMA, 50 microM), a compound that inhibits nitric oxide (NO) synthesis from L-Arg, was further added to the medium. These observations imply that cGMP production with possible involvement of a mechanism depending on NO synthesis may be functionally operating in the ganglionic tissue. Application of norepinephrine (NE, 50 microM) with pargyline, a monoamine oxidase inhibitor, to the medium also elevated the ganglionic cGMP level at a magnitude comparable to that shown by L-Arg addition, while co-addition of L-NMMA largely (approx. -60%) eliminated the NE-induced increase in ganglionic cGMP formation. In axotomized SCG one week prior to examination, where sympathetic neurons were degenerated and reactive proliferation of glial cells was in progress, augmented stimulatory effect (more than 8-fold) of NE on cGMP production was seen compared to that caused in unoperated ganglia or in SCG 1 week following denervation, where preganglionic cholinergic nerve terminals were destroyed. When axotomized SCG were transferred to in vitro incubation conditions, addition of an alpha-1 adrenergic antagonist, prazosin (1 microM) to the medium virtually reduced the accelerative effect of NE to less than 25% of the NE-induced cGMP level in the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid and transient alterations in transglutaminase activity in rat superior cervical ganglia following denervation or axotomy.

The activity of transglutaminase (TG), a Ca(2+)-dependent enzyme contributing to cross-linkage formation of intracellular polypeptide chains decreased rapidly to ca. 25% of control level in superior cervical ganglia (SCG) within 0.5 h following denervation. The reduced level was maintained for at least 24 h. By contrast, following axotomy, ganglionic TG activity increased by ca. 50% within 1 h, maintained the increase to 4 h, and returned to control level by 24 h. When SCG were transferred to aerobic in vitro incubation conditions 3 h following denervation, the addition of the protein kinase C (PKC) inhibitor, trifluoperazine (TFP, 10 micrograms/ml), to the medium partially reversed the denervation-induced reduction in ganglionic TG activity. Addition of a PKC activator, 12-O-tetradecanoylphorbol 13-acetate (TPA, 1 microM), had no effect on the TG activity. These findings suggest that the pathway resulting in the rapid, denervation-induced inhibition of TG activity may involve the transsynaptic activation of PKC. When SCG were placed in vitro 3 h following axotomy, addition of nerve growth factor (NGF, 0.25 micrograms/ml) to the medium reversed approximately one-half of the axotomy-induced increase in TG activity. Thus, following axotomy, the reduction in delivery to the SCG of NGF, which can be transported retrogradely within the axon and is indispensable for morphological and functional survival of sympathetic neurons, may trigger the transient, axotomy-induced TG activation in the SCG.

Selective alterations in transglutaminase activity of rat superior cervical ganglia in response to neurotransmitters, high potassium and sialic acid-containing compounds.

We examined the in vitro effects of neurotransmitters, high KCl as well as sialic acid-containing compounds (GM1; SC) on transglutaminase (TG) activity in isolated superior cervical ganglia (SCG) one week after denervation or axotomy. Following denervation, TG activity in SCG decreased to 83% of the unoperated control value, whereas that of axotomized ganglia was 28% of control. Thus, TG activity was relatively unaffected when sympathetic ganglionic neurons were preserved, but was markedly reduced under conditions where neurons were degenerating. Addition of ACh (0.1 mM) to the medium during aerobic incubation stimulated TG activity more than 3-fold in denervated ganglia but had no effect on TG activity in axotomized ganglia. Similarly, the NE (0.05 mM)-induced decrease of TG activity observed in intact SCG was also seen following denervation (-49%) but not following axotomy. In denervated SCG, the stimulatory effects of ACh were virtually abolished by co-addition of the cholinergic antagonists, atropine or hexamethonium, while the suppressant effects of NE were blocked by the adrenergic antagonists, propranolol, prazosin or yohimbine. These results imply that transmitter-induced rapid changes in TG activity occur predominantly in ganglionic neurons. When the ganglia were depolarized by high KCl (50 mM), a significant increase in TG activity in each intact, denervated and axotomized SCG was seen with qualitatively similar manner, suggesting that high KCl-induced depolarization affects both neuronal and glial components in the SCG. The marked increase in ganglionic TG activity in response to GM1 (5 nM) and synthetic SC (0.02 mM) were lost in denervated SCG but only partially reduced in axotomized SCG.(ABSTRACT TRUNCATED AT 250 WORDS)