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Biomedical subjects

S Alaluusua

Publications and source records attributed to S Alaluusua.

At least 19 recordsLinked to original sources

Lactational exposure of Han/Wistar rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin interferes with enamel maturation and retards dentin mineralization.

Exposure to environmental dioxins via mother's milk may be one causative factor of mineralization defects in children's teeth. A prerequisite for the completion of enamel mineralization is the removal of enamel matrix. To test the hypothesis that dioxins interfere with enamel maturation, we administered lactating Han/Wistar rats a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 50 or 1000 micro g/kg) on the day after delivery and analyzed tissue sections of the pup heads at post-natal days (Pn) 9 and 22. By Pn22, the first and second molars of the exposed pups, but not controls, showed retention of enamel matrix. Predentin was thicker than normal. Immunostaining for the aryl hydrocarbon/dioxin receptor (AhR) and cytochrome P4501A1 (CYP1A1) in ameloblasts and odontoblasts was reduced, suggesting that TCDD interferes with tooth mineralization via AhR. Extinction of AhR may lead to abolition of CYP1A1 expression as a sign of impaired dental cell function.

Ameloblasts↗

Long-term adverse effects on dentition in children with poor-risk neuroblastoma treated with high-dose chemotherapy and autologous stem cell transplantation with or without total body irradiation.

Chemo- and radiotherapy may have injurious effects on developing teeth. In this long-term follow-up study among poor-risk neuroblastoma (NBL) survivors our aims were: (1) to assess both the type and extent of the side-effects of the anticancer treatment on tooth development; and (2) to develop an index for expressing total damage to the permanent dentition. We studied the dental development from panoramic radiographs (PRG) of 18 long-term survivors treated under the age of 6 years with high-dose (HD) chemotherapy and autologous stem cell transplantation (ASCT) for poor-risk NBL. The myeloablative therapy was either HD chemotherapy and fractionated total body irradiation (TBI) of 10-12 Gy (TBI group, n = 10) or HD chemotherapy only (non-TBI group, n = 8). A defect index (DeI) was developed to describe the damage to the permanent dentition. The DeI was also tested in 18 healthy adolescents. All NBL patients had disturbances in dental development including short roots, arrested root development, microdontia and tooth aplasia. After TBI, 9/10 patients had very severe root defects, in contrast to none in the non-TBI group. All children in the TBI group had 2-12 (mean 6.6) missing permanent teeth, while 2/5 in the non-TBI group (3/8 excluded due to young age) had two and four missing permanent teeth, respectively. Microdontia was found at equal frequency in both groups. The mean value of the DeI was 70.0 (range 28-117) in the TBI group, 15.2 (range 4-34) in the non-TBI group (P<0.001, Mann-Whitney U test) and 1.8 (range 0-15) in healthy adolescents. Disturbances in dental development may compromise occlusal function in poor-risk NBL patients after ASCT, especially when TBI is included in the conditioning regimen. Long-term dental follow-up and rehabilitation is required.

Adolescent↗

In utero/lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure impairs molar tooth development in rats.

Developmental defects caused by dioxins are causing increasing concern since they occur at low dose levels and are usually permanent. In this study we examined the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at low in utero/lactational exposure levels on rat tooth development in three rat lines, denoted A, B, and C, that differ in their TCDD sensitivity and aryl hydrocarbon receptor structure. These rat lines are derived from TCDD-resistant Han/Wistar (Kuopio) and TCDD-sensitive Long-Evans (Turku/AB) rats by selective breeding. The main target teeth were the third molars, since their development spans from the perinatal period to about 6 weeks after birth. Pregnant dams were exposed to 0.03-1 microg/kg TCDD on gestation day 15. Pups exposed in utero and lactationally were euthanized at the age of 5 or 10 weeks and the jaws were examined. The eruption of the third molar was observed by stereomicroscopy and the jaws were further radiographed. TCDD at 1 microg/kg completely prevented the development of the third lower molars in 60% of males and 50% of females in the most sensitive rat line, C, while only 6% or less of the pups in the more resistant lines A and B were lacking this target tooth. TCDD exposure also dose-dependently diminished the proportion of third molars erupted at the age of 5 weeks. The size of molars was dose-dependently reduced in all rat lines. The third lower molars were most severely affected, and the reduction was significant already at 0.03 microg/kg in line A and at 0.1 microg/kg in lines B and C. The results indicate that impaired tooth development is one of the most sensitive endpoints of TCDD-induced toxicity.

Abnormalities, Drug-Induced↗

Arrest of rat molar tooth development by lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The interference with tooth development by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was studied in dioxin-resistant Han/Wistar rats. Lactating dams were given a single dose of 50 or 1000 microg TCDD/kg body wt 1 day after delivery and the pup heads were analyzed radiographically or histologically at postnatal days 9 and/or 22. Of 19 animals studied histologically, 10 lacked one or more third molars, which were at the bud stage at the start of the experiment. A higher proportion of pups exposed to the higher dose (9/13) lacked third molars than those exposed to the lower dose (1/6) (27/52 and 2/24 teeth missing, respectively). Missing upper third molars (19/38) were more frequent than were lower (10/38). The development of the third molars present was retarded. The root tips of the more advanced first and second molars were prematurely closed and root formation was arrested, but eruption was not affected. Dentinogenesis of the continuously erupting lower incisor teeth was preeruptively arrested because of pulpal cell death. All the teeth of the control rat pups developed normally. In contrast to the control pups, none of the 11 experimental pups examined radiographically (6 exposed to the higher dose and 5 to the lower) showed mineralization of their third molar cusps. The results show that the effects of TCDD on rat tooth development depend on not only the dose but also the tooth type and developmental stage. Inasmuch as early tooth development is under the control of inductive interactions between the epithelium and the mesenchyme, the interference by TCDD with tooth morphogenesis with the consequent arrest of development is likely to involve epithelial-mesenchymal signaling.

Animals↗

Identification of a nonsense mutation in the PAX9 gene in molar oligodontia.

Development of dentition is controlled by numerous genes, as has been shown by experimental animal studies and mutations that have been identified by genetic studies in man. Here we report a nonsense mutation in the PAX9 gene that is associated with molar tooth agenesis in a Finnish family. The A340T transversion creates a stop codon at lysine 114, and truncates the coded PAX9 protein at the end of the DNA-binding paired-box. All the affected members of the family were heterozygous for the mutation. The tooth agenesis phenotype involves all permanent second and third molars and most of the first molars and resembles the earlier reported phenotype that was also associated with a PAX9 mutation. The phenotype is presumably a consequence of haploinsufficiency of PAX9. In another Finnish family with molar tooth agenesis, we could not find similar sequence changes in PAX9.

Adult↗

Dental caries is common in Finnish children infected with Helicobacter pylori.

Childhood factors such as low socioeconomic status are risk factors for Helicobacter pylori infection and Streptococcus mutans-related dental caries. We examined whether H. pylori infection and dental caries are present today in the same group of children examined previously. We reviewed the public dental health service files of 21 H. pylori-positive children (upper gastrointestinal endoscopy at a median age of 13.5 y) and 27 H. pylori-negative children (endoscopy at a median age of 12.5 y) examined during 1995-98 at the Helsinki University Central Hospital, Finland. All H. pylori-positive children had experienced dental caries in their primary or permanent teeth or in both whereas among H. pylori-negative children the respective proportion was 70% (p < 0.01). At the age of 7 y, 18% (3/17) of the H. pylori-positive children had experienced caries in permanent teeth as compared to 0% among H. pylori-negative children (0/24; p < 0.05). At the age of 12 y, H. pylori-positive children had more decayed, missing or filled permanent teeth than H. pylori-negative children (80% vs. 38%; p < 0.05). Although a causal relationship between H. pylori and dental caries is unlikely, it is possible that H. pylori-infected children have an increased risk of other health problems, such as dental caries, for which proper treatment is needed.

Adolescent↗

Actinobacillus actinomycetemcomitans serotype e--biotypes, genetic diversity and distribution in relation to periodontal status.

Actinobacillus actinomycetemcomitans isolates from 356 individuals were screened for identification of serotype e in order to investigate its distribution in relation to periodontal status. From subjects with serotype e, 1-6 isolates per subject (n = 61) were genotyped using arbitrarily primed-polymerase chain reaction (AP-PCR) and apaH gene polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis to determine the genetic heterogeneity within the serotype. Furthermore, one serotype e strain per subject was tested for fermentation of 8 carbohydrates for biotyping. Among patients with adult periodontitis (n = 219), localized juvenile periodontitis (n = 55) and other forms of early-onset periodontitis (n = 18) serotypes b, a and c, respectively, were the most frequently detected serotypes. Non-periodontitis subjects (n = 64) were predominantly colonized with serotype c. Serotype e was found in 30 (14%) adult periodontitis patients, 2 (11%) early-onset periodontitis patients and in 5 (8%) non-periodontitis individuals, but in none of the 55 localized juvenile periodontitis patients. AP-PCR distinguished 3 and apaH gene PCR-RFLP analysis 2 genotypes among the 61 A. actinomycetemcomitans serotype e isolates, one genotype per subject. The AP-PCR genotypes 1 and 3 represented the apaH genotype 1 and the AP-PCR genotype 2 the apaH genotype 2. On the basis of variable fermentation of galactose and xylose, 3 biotypes among A. actinomycetemcomitans serotype e were established. Contrary to the absence of A. actinomycetemcomitans serotype e in localized juvenile periodontitis patients, its detection frequency was comparable among other forms of periodontitis and periodontal health. Clinical serotype e isolates form at least 2 genetic types and 3 biotypes.

Adolescent↗

Persistence of oral colonization by the same Actinobacillus actinomycetemcomitans strain(s).

BACKGROUND: The Gram-negative facultatively anaerobic coccobacillus Actinobacillus actinomycetemcomitans is the major pathogen in localized juvenile periodontitis (LJP) and some forms of adult periodontitis (AP). A. actinomycetemcomitans can be grouped into 5 serotypes (a through e) based on differences in the carbohydrate moiety of cell surface lipopolysaccharide. The A. actinomycetemcomitans population is genetically heterogeneous. Since the studies on A. actinomycetemcomitans colonization have mostly applied only culture techniques, the clonality of the follow-up isolates has not been established. Thus, it is possible that, although A. actinomycetemcomitans could be repeatedly isolated from an individual, the initial colonizing strain was replaced by another strain. The aim of the study was to determine whether oral A. actinomycetemcomitans strains change spontaneously over time or after periodontal treatment. METHODS: A total of 922 A. actinomycetemcomitans isolates were recovered from 115 subjects. From each subject A. actinomycetemcomitans isolates were obtained from 2 to 9 follow-up samples 0.5 to 11.5 years apart. After the first sampling occasion, 99 subjects were treated for either LJP or AP, whereas the 16 non-periodontitis subjects received no treatment. All A. actinomycetemcomitans isolates were serotyped and 235 isolates from 52 subjects genotyped with AP-PCR and/or with ribotyping. RESULTS: Isolates of only one serotype, or non-serotypeable isolates alone, were repeatedly found in 104 subjects; serotype a occurred in 25%, b in 33%, c in 23%, d in 5%, e in 7%, and non-serotypeable isolates in 8% of these subjects. Two serotypes (or serotypeable isolates together with non-serotypeable isolates) occurred simultaneously in 9 subjects and in each of these subjects at least one of the serotypes was detected at each sampling occasion. In one subject the initial serotype reappeared although a different serotype was once seen alone, whereas in another subject the initial serotype could not be recovered later. Identical genotypes of A. actinomycetemcomitans were repeatedly detected in each of 52 subjects with follow-up isolates of the same serotype. CONCLUSIONS: The results showed that spontaneous or treatment-induced change in the oral A. actinomycetemcomitans strain(s) is extremely rare and that colonization with the same strain(s) seems to be remarkably persistent.

Adolescent↗

Mutacin production by Streptococcus mutans may promote transmission of bacteria from mother to child.

The production of bacteriocin-like inhibitory substances, mutacins, by mutans streptococci varies among isolates. To find if the degree of mutacin activity of an isolate was related to its transmission between mother and her child, 19 mothers and their 18-month- to 3-year-old children were sampled for their oral mutans streptococci. In addition, the stability of mutacin activity was studied with isolates from the mothers and with isolates from five unrelated 5-year-old children in 5- to 7-year follow-up studies. A total of 145 oral mutans streptococcal isolates were serotyped by immunodiffusion, ribotyped, and mutacin typed by the stab culture technique. Mutacin was produced by 88% of the strains against more than 1 of the 14 indicator strains, representing mutans streptococci, Streptococcus sanguis, Streptococcus salivarius, Streptococcus oralis, Streptococcus gordonii, and Streptococcus pyogenes. Streptococcus mutans isolates showed more inhibitory activity than did Streptococcus sobrinus isolates. Identical ribotypes had similar mutacin activity profiles within a subject, initially and in the follow-up studies, in all but two cases. The mothers harbored a total of 37 different mutans streptococcal ribotypes. Six children were negative for mutans streptococci. Transmission was probable in 9 of 20 mother-child pairs on the basis of the presence of identical strains, as determined by ribotyping and bacteriocin (mutacin) typing. S. mutans strains shared between a mother and her child showed a broader spectrum of inhibitory activity than did nontransmitted strains. In conclusion, the mutacin activity of clinical isolates is reasonably stable, and this virulence factor seems to be of clinical importance in early colonization by S. mutans.

Adolescent↗

Detection of Porphyromonas gingivalis from saliva by PCR by using a simple sample-processing method.

Simple sample-processing methods for PCR detection of Porphyromonas gingivalis, a major pathogen causing adult periodontitis, from saliva were studied. The ability to detect P. gingivalis from 118 salivary samples by PCR after boiling and Chelex 100 processing was compared with bacterial culture. P. gingivalis was detected three times more often by PCR than by culture. Chelex 100 processing of saliva proved to be effective in preventing PCR inhibition and was applied to determine the occurrence of P. gingivalis in saliva samples from 263 Finnish subjects between 5 and 80 years of age. The occurrence of P. gingivalis increased with age, and it was detected by PCR in the saliva of 5.0% of subjects between 5 and 10 years of age, 13.8% of subjects between 11 and 20 years of age, 13.4% of subjects between 21 and 30 years of age, and 63.3% of subjects between 31 and 80 years of age. The results indicate that P. gingivalis is a rare finding in saliva from periodontally healthy children and young adults but a frequent one in saliva from adult periodontitis patients.

Adolescent↗

Characterization of serologically nontypeable Actinobacillus actinomycetemcomitans isolates.

Our previous studies have shown that Actinobacillus actinomycetemcomitans isolates of a given arbitrarily primed PCR (AP-PCR) genotype belong to the same serotype (of serotypes a through e). In the present study we investigated whether the AP-PCR genotypes of nonserotypeable A. actinomycetemcomitans isolates match those of the serotypeable isolates. The isolates were additionally characterized by restriction analysis of the apaH PCR amplification products. The material included 75 nonserotypeable and 18 serotypeable A. actinomycetemcomitans isolates from 34 epidemiologically unrelated subjects. The serotypeable isolates were obtained from subjects who also harbored nonserotypeable isolates. Eight AP-PCR genotypes were distinguished among the isolates; six genotypes matched those detected in our previous studies, whereas two genotypes were new. Intraindividually, the A. actinomycetemcomitans isolates produced identical AP-PCR banding patterns, regardless of whether they were serotypeable or nonserotypeable, in 22 of 23 subjects participating with multiple isolates. AP-PCR genotype 3, corresponding to serotype c, was by far the most common among the nonserotypeable isolates (62% of subjects). Results obtained with the apaH restriction analysis confirmed the results obtained with AP-PCR for 31 of the 34 subjects. The results suggest that nonserotypeable A. actinomycetemcomitans isolates originate from serotypeable isolates, especially from serotype c isolates, and the likelihood of the existence of additional serotypes is small.

Actinobacillus Infections↗

Epidermal growth factor receptor as a mediator of developmental toxicity of dioxin in mouse embryonic teeth.

We have previously shown that dioxins at prevailing levels in mothers' milk may cause mineralization defects in the developing teeth of their children. Developmental dental defects have also been reported in rhesus macaques and rats experimentally exposed to dioxin. The most toxic dioxin congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is a potent modulator of epithelial cell growth and differentiation. To clarify whether epidermal growth factor receptor (EGFR), implicated in the mediation of the developmental toxicity of TCDD, is involved in dental toxicity, we cultured embryonic molar teeth from EGFR-deficient mice with TCDD, epidermal growth factor (EGF), and both agents in combination. In teeth of the normal embryos, TCDD caused depolarization of odontoblasts and ameloblasts. Consequently, the dentin matrix failed to undergo mineralization, the enamel matrix was not deposited, and cuspal morphology was disrupted. In teeth of the null mutant embryos, only the cuspal contour was mildly modified. EGF alone retarded the molar tooth development of normal embryos, but not that of EGFR-deficient embryos. When coadministered with TCDD, EGF for the most part prevented the adverse effects of TCDD on teeth of the normal embryos. These results show that the interference of TCDD with mouse molar tooth development in vitro involves EGFR signaling. Thus, EGFR may also play a role in the developmental defects that dioxins cause in human teeth. Because EGFR is widely expressed in developing organs, EGFR signaling may even be of general relevance in the mediation of the developmental toxicity of TCDD.

Animals↗

Production of glucosyltransferases by clinical mutans streptococcal isolates as determined by semiquantitative cross-dot assay.

Forty-four clinical isolates of mutans streptococci were examined by a semiquantitative cross-dot assay for in vitro production of glucosyltransferases GTF-I, GTF-SI and GTF-S of Streptococcus mutans, and GTF-I of Strep. sobrinus, using monospecific antibodies. The isolates were obtained from 12 1.5- to 3-year old children, six caries-active and six caries-free, and from their mothers. The isolates were selected originally from 243 isolates and they represented 35 genetically distinct types as analysed by serotyping and ribotyping. 27 isolates were of serotype c, nine of serotype e and eight of serotype g. Mother child pairs shared nine ribotypes, suggesting vertical transmission. The results showed that, when cultured in Todd-Hewitt broth supplemented with 1% glucose, all Strep. mutans isolates produced GTF-I and GTF-S and all except two produced GTF-SI of Strep. mutans. All Strep. sobrinus isolates produced GTF-I of Strep. sobrinus. The Strep. mutans GTF-I, GTF-SI and GTF-S production of isolates exhibiting a different ribotype showed variability. The variability of GTF-SI and GTF-S production was less pronounced for serotype e isolates. The GTF-I production by Strep. sobrinus isolates did not vary. Transmitted strains produced the same levels of GTFs as strains that were distinct (not transmitted). Strep. mutans isolates of caries-active children produced the same levels of GTF-I and GTF-S, but tended to produce lower levels of GTF-SI than isolates of caries-free children. In conclusion, the results suggested that Strep. mutans isolates exhibiting a different ribotype often had differences in production of GTFs. However, no clear superiority of the high-producer over the low-producer strains was found in regard to their colonization or caries promotion in young children.

Adult↗

Phenotypic and genotypic characterization of oral yeasts from Finland and the United States.

A total of 4-22 isolates of oral yeasts per subjects from 48 yeast-positive Finnish and American subjects (25 females and 23 males) were phenotyped and genotyped to determine the frequency of simultaneous oral carriage of multiple yeast taxa. An oral sample from either periodontal pockets, oral mucosa or saliva was obtained. All subjects yielded Candida albicans and 3 subjects an additional yeast species (Candida krusei, Candida glabrata or Saccharomyces cerevisiae). The API 20C Aux kit distinguished 9 different carbohydrate assimilation profiles among the C. albicans isolates. Thirty-eight of 46 C. albicans biotype I isolates were categorized in a single numerical profile. PCR analysis, using a random primer OPA-03 and a repetitive primer (GACA)4, detected 2 major genotypic groups among the C. albicans isolates; 44 subjects showing isolates with a "typical" PCR-profile and 4 subjects isolates with an "atypical" PCR-profile. The "atypical" PCR-profile was similar to that of Candida dubliniensis. All C. albicans isolates assimilated xylose, except 5, including the 4 with an "atypical" PCR-profile. No difference was found in distribution of oral yeast species, and of C. albicans phenotypes and genotypes between Finnish and American subjects. The present PCR method may offer a rapid and easy means of distinguishing oral Candida species.

Adult↗

Periodontitis patient and the spouse: periodontal bacteria before and after treatment.

Suspected periodontal pathogens can be transmitted between spouses. The treatment response may be unsuccessful in periodontitis patients, if the spouse harbors these bacteria. The aim of the present 6-month follow-up study was to clarify whether the microbiological treatment outcome of periodontitis patients is related to the detection of suspected periodontal pathogens in the saliva of the spouse. 10 patients with advanced periodontitis and their spouses were included in the study. The patients received mechanical periodontal treatment and 500 mg metronidazole systemically 2x a day for 7 days. The presence of visible plaque, gingival bleeding after probing, suppuration, supragingival and subgingival calculus and pocket depths were assessed at baseline and 1 and 6 months after treatment. Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia/Prevotella nigrescens, Campylobacter rectus and Peptostreptococcus micros were cultured from pooled subgingival samples from the patients and from salivary samples from the spouses at corresponding occasions. Periodontal conditions in the patients improved after treatment as determined by the significantly lower values of clinical variables 1 and 6 months after treatment compared to those at baseline. However, the re-emergence of periodontal bacteria after treatment of the patients was not related to the concurrent detection of the respective bacteria in the saliva of the spouses. In this study design, it seemed that the salivary bacterial load in the spouse was of minor importance for the microbiological treatment outcome of the patient.

Aggregatibacter actinomycetemcomitans↗

Can one acquire periodontal bacteria and periodontitis from a family member?

Recent findings suggest that two major periodontal pathogenes, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, are transmitted among family members. The authors discuss the evidence of person-to-person transmission of periodontal bacteria, the significance of saliva as a vehicle of transmission and the methods of verifying clonal similarity of bacterial strains obtained from family members. The authors also discuss the prophylactic and therapeutic implications of the person-to-person spread of periodontal bacteria.

Adult↗