A network approach to orthodontic diagnosis.

BACKGROUND: Network analysis, a recent advancement in complexity science, enables understanding of the properties of complex biological processes characterized by the interaction, adaptive regulation, and coordination of a large number of participating components. OBJECTIVE: We applied network analysis to orthodontics to detect and visualize the most interconnected clinical, radiographic, and functional data pertaining to the orofacial system. MATERIALS AND METHODS: The sample consisted of 104 individuals from 7 to 13 years of age in the mixed dentition phase without previous orthodontic intervention. The subjects were divided according to skeletal class; their clinical, radiographic, and functional features were represented as vertices (nodes) and links (edges) connecting them. RESULTS: Class II subjects exhibited few highly connected orthodontic features (hubs), while Class III patients showed a more compact network structure characterized by strong co-occurrence of normal and abnormal clinical, functional, and radiological features. Restricting our analysis to the highest correlations, we identified critical peculiarities of Class II and Class III malocclusions. CONCLUSIONS: The topology of the dentofacial system obtained by network analysis could allow orthodontists to visually evaluate and anticipate the co-occurrence of auxological anomalies during individual craniofacial growth and possibly localize reactive sites for a therapeutic approach to malocclusion.

Vitamin D-binding protein in the perinatal period.

The molecular polymorphism and quantitative levels of serum vitamin D-binding protein (DBP) were ascertained in a group of preterm, full-term and hypocalcaemic full-term newborn infants. The serum concentration of DBP is not influenced by phenotype and increases with fetal age from the 32nd-33rd week of gestation until the 35th week of gestation. Neither different DBP allele distribution nor abnormal quantitative levels found among 29 hypocalcaemic full-term newborn infants.

Transferrin subtypes in cystic fibrosis.

The molecular polymorphism and quantitative data of serum transferrin (Tf) were ascertained in a group of fibrocystic patients, their parents and controls. Quantitative rates of pre-albumin, retinol binding globulin (RBG) and alpha-1-glycoprotein were also investigated as a reference for the evaluation of Tf quantitative data. Neither different allele distributions nor abnormal electrophoretic patterns were observed among CF patients. A slight lowering of Tf, pre-albumin and RBG, probably due to malnutritional condition in CF subjects was found.

Silver-stained phenotyping of alpha 1-antitrypsin in dried blood and serum specimens.

In this technique for determining the electrophoretic phenotype of alpha 1-antitrypsin in dried blood or serum specimens, the adsorbed material is eluted with a concentrated solution of dithiothreitol, focused on polyacrylamide thin-layer gel, and made visible with silver stain. With this staining technique all normal and pathological alpha 1-antitrypsin phenotypes can be detected. The procedure is relatively simple, inexpensive, and suitable for use in large-scale screening for alpha 1-antitrypsin deficiency in selected populations.

Group-specific component subtypes along the Italian Peninsula.

Nine areas in Italy were analyzed for the frequencies of the Gc system (group-specific component). No significant discrepancy was found among their frequencies as they resulted after isoelectric focusing (IEF). When more accurately analyzed, gene frequencies revealed a microheterogeneity affecting one sample (city of Bari) against eight tightly clustered values.

Rapid resolution of transferrin C subtypes through isoelectric focusing with 2-mercaptoethanol.

The technique of choice currently used for the detection of serum transferrin molecular polymorphism is isoelectric focusing on polyacrylamide slab gels. However, this procedure is unsatisfactory for routine purposes, since a long pretreatment of the serum with iron-donor compounds or neuraminidase is necessary in order to obtain a complete resolution of the transferrin molecule. A very fast and highly economical standardized procedure for transferrin typing which enables a fair molecular resolution within only 3 1/2 h is reported. Protracted pretreatment of serum with neuraminidase or with iron-donor compounds can be totally avoided. An ultrathin layer of polyacrylamide gel is employed for the run, using pH ranges of 4-6.5 or 5-7. A short pretreatment of serum with a 13% solution of 2-mercaptoethanol is performed before the samples are placed on the gel. This technique has been used to perform transferrin typing in 396 cord serum samples from newborn infants of Arezzo (Tuscany), without occurrence of artifacts or the appearance of extra bands in transferrin patterns.

Transferrin: common and rare variants in italy. Evidence for the existence of the rare TfC6 among Caucasians.

The results of a large screening for the transferrin polymorphism in five different areas of Italy (3099 cases) are given. Frequencies of common types were similar to those of already known Caucasian populations. Among rare types TfB were more frequently observed than TfD. Evidence is given for the existence of the TfC6 allele in Caucasians. A family group analysis of some rare types was done.

Transferrin C subtypes in extremely premature newborn infants.

Genetic typing of serum transferrin was performed in a group of 88 extremely premature infants (gestation age less than 32 wk) and in a control group of 351 full-term infants, using isoelectric focusing technique on ultrathin layer of polyacrilamide gel. A major incidence of C2 type was found among the preterm infants when compared to full-term infants X2 = 22,86, (P less than 0.001). In view of the previously reported higher incidence of this phenotype in women prone to spontaneous abortion, a selective mechanism associated with this serum transferrin type promoting spontaneous abortion and preterm delivery, seems to occur. The relative risk of preterm delivery were calculated to 1.4 and 8.3 for the C2-1 and C2 types, respectively. Supportive evidence in favour of this hypothesis is offered by the correlation existing between transferrin C2 allele and placental alkaline phosphatase variant F, the latter being associated with increased risk of spontaneous abortion.

Serum protease inhibitory capacity. (Recent knowledge on alpha 1-antitrypsin deficiency).

The molecular structure and the serum levels of alpha 1-antitrypsin, the major antiprotease of human serum, are controlled by a series of codominant alleles at a single chromosomal locus, known as the Pi(protease-inhibitor) locus. The congenital deficiency of this inhibitor is known to be associated with the development of lung emphysema in early adulthood and chronic liver disease in childhood. Less frequent associations have been reported, such as rheumatoid arthritis, membranoproliferative glomerulonephritis and mosaicism for sex chromosomes. The identification of several suballeles of the Pi system, which was accomplished by means of a refinement of the isoelectric focusing technique, has promoted research concerning their possible pathogenic implications. The studies so far performed have often led to contradictory results, but nevertheless they strongly ascribe the property of controlling the quantitative levels of alpha 1-antitrypsin to certain M subtypes. Intermediate M3 subtype has recently been associated with the development of chronic obstructive lung disease in adulthood. Should this finding be confirmed by further evidence, a new approach to the prevention of lung disease could be considered, given that 30% of the individuals are carriers of the M3 suballele. In Italy, the incidence of congenital deficiency of alpha 1-trypsin appears to be greater in the northern regions, where 15-20 out of every 100,000 individuals are affected by the severe (ZZ) form of the deficiency.

PiM subtypes in bronchiolitis.

Decreased alpha-1-antitrypsin (alpha 1AT) levels have been observed in children affected by bronchiolitis; however, variant alleles Pi (S, Z) which are usually associated with reduction of the inhibitor do not show a higher incidence in children affected by this disease. Subtypes M2 and M3 of alpha 1AT have recently been considered to play a role in the development of allergic states in children as well as in chronic obstructive lung disease in adults. In the present study we have investigated the incidence of PiM subtypes in 98 children affected by bronchiolitis. No greater incidence of subtypes M2 and M3 was observed in these children than in controls. These results rule out the hypothesis of a pathogenetic role of M subtypes in the development of bronchiolitis in children.

Improved typing of human serum transferrin by isoelectric focusing on ultrathin layer polyacrylamide slab gels.

An improved method for separating transferrin subtypes through the use of isoelectric focusing on ultrathin layer polyacrylamide gels is described. The most considerable problems encountered in the assessment of the Tf phenotypes after pretreatment with iron donor compounds are pointed out. Useful technical devices for reducing the occurrence of artifactitious extrabands are suggested. Finally, the gene frequencies in three samples from Italian populations are reported.

Alpha-1-antitrypsin (alpha 1AT) phenotypes and PiM subtypes in Italy. Evidence of considerable geographic variability.

Genetic typing of alpha 1AT was performed in 3751 individuals from Italian towns. The following was observed: (a) The pathologic phenotypes (SZ, MZ, ZZ) appeared to decrease progressively from northern to southern Italy; (b) the distribution of the PiM suballeles showed considerable geographic variability, but the suballele M2 was more frequently encountered in southern Italy; and (c) in the large cities of southern Italy, the frequency of the deficiency more closely resembled that found in northern Italy than that of the remaining populations of the south.

Characterization of alpha-1-antitrypsin by isoelectric focusing on an ultrathin polyacrylamide gel layer. An economic high-resolution system for determining PiM subtypes.

Through the use of ultrathin layer polyacrylamide gel isoelectric focusing it is possible to obtain a resolution of the bands of alpha 1AT so as to be able to easily recognize all six PiM subtypes. The optimal resolution of the PiM subtypes is obtained without deforming the pattern of the Pi phenotypes. In addition to high resolution, ultrathin layer polyacrylamide gel isoelectric focusing permits a notable reduction of fees to 1/5 of the usual.

Alpha-1-antitrypsin in umbilical cord serum: pi phenotypes and relationships with idiopathic respiratory distress syndrome.

The concentrations and phenotypes of serum alpha-1-antitrypsin (alpha1AT) were determined in 650 newborn infants. The distribution of these 650 subjects among the various Pi phenotypes confirms the higher frequency reported for the PiS allele in Latin populations. Serum alpha1AT levels vary between one phenotype and the other. Besides, at birth, infants weighing more than 2,500 g have alpha1AT levels significantly higher (P less than 0.001) than infants weighing less than 2,500 g; this difference in serum alpha1AT concentrations is due to the low alpha1AT levels found in preterm infants. The significantly lower alpha1AT concentrations found in preterms is associated with a higher risk of developing IRDS and with a mean birth weight under 2,000 g. Infants who develop IRDS frequently have lower alpha1AT levels than those who do not develop the syndrome, independently from body weight. On the basis of serum alpha1AT quantitation, newborn infants may be separated into two groups, characterized respectively by concentrations above or below 150 mg%. From our data, it appears that if the group with an alpha1AT concentration lower than 150 mg% is phenotyped, it is possible to differentiate infants with a high risk of fatal IRDS from individuals with a "pathological" phenotype.

Alpha-1-antitrypsin phenotypes in newborns from Central and Southern Italy.

The results of Pi typing on 500 infants from Central and Southern Italy are reported. Phenotype determinations were performed on umbilical cord serum. We observed nine different phenotypes; each of these is present in other European populations. The frequencies of the Pi alleles in our group were found to be, on the whole, comparable to those found in other populations widely separated geographically. However, the frequency of the Pi S gene in our sample (0.0670) was greater than that observed in Northern and Central European and American groups. Our Pi S frequency was similar to that found in a French group and lower than that of Spanish and Portuguese groups. Our data thus confirm the higher Pi S gene frequency in Latin populations.