Oral Rehabilitation of a Patient With Amelogenesis Imperfecta

A patient with Type I hypoplastic patterned amelogenesis imperfecta, subtype D, presented for prosthodontic evaluation. This article describes the developmental and pathophysiological background of this disease. A clinical report describing the diagnosis, treatment planning, and dental rehabilitation of the patient is reviewed.     

The chemotherapy of posterior Fossa tumors in childhood

Conventional therapy for brain tumors, consisting of neurosurgical intervention and radiotherapy, has not resulted in the successes achievable in other childhood malignancies. The role of adjuvant chemotherapy, well defined in many childhood cancers, has not yet contributed significantly to the treatment of children with brain tumors. Chemotherapy of recurrent tumors has produced regressions but no cures. The most active agents identified to date in the treatment of recurrent posterior fossa tumors include cisplatinum, cyclophosphamide and methotrexate. Future efforts will need to focus on the rational selection of drugs for study in limited agent histology-stratified phase II trials, with advancement of active agents into large randomized phase III adjuvant therapy trials.     

Integration of the cytogenetic and physical maps of chicken chromosome 17

The chicken genome, like those of most avian species, contains numerous microchromosomes that cannot be distinguished by size alone. Unique properties attributed to the microchromosomes include high GC content and gene density, and an enhanced recombination rate. Previously, microchromosome GGA 17 was shown to align with the consensus genetic linkage group E41W17, and bacterial artificial chromosome (BAC) clones containing E41W17 markers were isolated and assigned on the physical BAC map as well as the recently assembled draft chicken genome sequence. For this study, these same BACS were utilized as probes for fluorescence in-situ hybridization (FISH) to develop the GGA 17 cytogenetic map. Here we detail the chromosome order of ten BAC DNAs, thereby deriving a cytogenetic map of GGA 17 that is simultaneously integrated with both the linkage map and genome sequence. The location of the FISH probes together with the morphological appearance of the chromosome suggested that GGA 17 is an acrocentric chromosome whose cytogenetic map orientation is reversed from that currently indicated by the linkage map and draft genome sequence. The reversed orientation and the centromere location of GGA 17 were confirmed experimentally by dual-colour FISH hybridization using terminal BACs and the centromere-specific CNM oligonucleotide as probes. An advantage of this cyto-genomic approach is the improved alignment of the sequence and linkage maps with cytogenetic features such as the centromere, telomeres, p and q arms, and staining patterns indicating GC versus AT content.     

Growth of native Hawaiian school children: I. Research design,stature, and weight measurements

A semilongitudinal survey of the growth of native Hawaiian school children, focused on the development of fatness, has been carried out on the Island of Hawaii. Four cohorts of children, first studied in grades one, four, seven, and ten, were measured annually for four years. Several factors, including percentage of Polynesian ancestry, identification with Hawaiian culture, socioeconomic status, dietary intake, and physical fitness, have been considered for their potential relationship to the development of fatness Data presented here indicate that native Hawaiian boys tend to be taller for their age than NHANES-II medians until age 14 years, but are not significantly taller than their non-Hawaiian classmates. Native Hawaiian boys and girls are heavier for their age than NHANES-II medians at most ages and are significantly heavier than non-Hawaiian classmates. Percentage of Polynesian ancestry is a significant predictor variable of both stature-for-age and weight-for-age among native Hawaiian children in the first and fourth grade cohorts. Study of fatness in a genetically heterogeneous Polynesian population that is relatively homogeneous in regard to modernization may yield insights into genetic contributions to the problem of obesity among Pacific Islanders.     

Identification of two point mutations and a one base deletion in exon 19 of the dystrophin gene by heteroduplex formation

Two thirds of the Duchenne muscular dystrophy population haveeither gene deletions or duplications. The nondeletion/duplicationcases are most likely the result of point mutations or smalldeletions and duplications that cannot be easily identifiedby current strategies. The major obstacle in identifying smallmutations is due to the large size of the dystrophin gene. Weselectively screened 5 DMD exons containing CpG dinucleotidesin 110 DMD patients without detectable deletions or duplications.Nonsenses mutations are frequently due to a C- to -T transitionwithin a CG dinucleotide pair. To screen for the nonsense mutations,we used the heteroduplex method. Utilizing this approach, weidentified 2 different nonsense mutations and a single basedeletion all occurring in exon 19. This is the first reportof a clustering of small mutations in the the dystrophin gene.     

Impact of intranasal budesonide on immune inflammatory responses and epithelial remodeling in chronic upper airway inflammation

BACKGROUND: Histologic and immunohistologic features of nasal polyps (NP) are similar to those observed in asthma, thus suggesting a similar immunopathology. OBJECTIVE: The primary objective of this study was to further understand the anti-inflammatory and immunoregulatory effects of locally delivered corticosteroids. To this end, the effect of intranasal budesonide on the expression of specific cytokines, lymphocyte subsets, and epithelial remodeling in this model of airway tissue inflammation were studied. METHODS: We used immunohistochemical techniques to examine nasal mucosae (NM) from healthy individuals and nasal polyp (NP) tissues from patients with nasal polyposis obtained before and after intranasal budesonide treatment. RESULTS: First, the density of CD8(+) cells was markedly increased in NP tissues after intranasal budesonide treatment from 16.1 +/- 8.4 (M +/- SEM) per mm(2) to 39.9 +/- 24.1. Second, the density of cells immunoreactive for IL-4, IL-5, IFN-gamma, IL-12, and TGF-beta in NP was significantly greater than in control NM tissues. The density of IL-4(+) and IL-5(+) cells in NP tissues significantly decreased after budesonide treatment from 40 +/- 12 to 17.8 +/- 8 and from 19.3 +/- 11 to 10.4 +/- 7, respectively. In contrast, the density of IFN-gamma(+) and IL-12(+) cells remained unchanged. In addition, we found that the density of TGF-beta(+) cells significantly increased after intranasal budesonide from 18 +/- 5 to 41 +/- 9. Third, damage to the entire length of the NP epithelium was quantified using a grading system. The epithelium of untreated NP was substantially damaged; remarkable epithelial restitution with no apparent changes in stromal collagen deposition was observed after intranasal budesonide treatment. CONCLUSIONS: These findings demonstrate that intranasal budesonide induced an increase in CD8 population and a selective regulatory effect on tissue cytokine expression. Furthermore, intranasal budesonide promoted epithelial remodeling. We hypothesize that these immunoregulatory and remodeling effects elicited by steroids might be, at least in part, mediated by the induction of TGF-beta.     

Characterization of a novel leucine-rich repeat protein antigen from group B streptococci that elicits protective immunity

Group B streptococci (GBS) usually behave as commensal organisms that asymptomatically colonize the gastrointestinal and urogenital tracts of adults. However, GBS are also pathogens and the leading bacterial cause of life-threatening invasive disease in neonates. While the events leading to transmission and disease in neonates remain unclear, GBS carriage and level of colonization in the mother have been shown to be significant risk factors associated with invasive infection. Surface antigens represent ideal vaccine targets for eliciting antibodies that can act as opsonins and/or inhibit colonization and invasion. Using a genetic screen for exported proteins in GBS, we identified a gene, designated lrrG, that encodes a novel LPXTG anchored surface antigen containing leucine-rich repeat (LRR) motifs found in bacterial invasins and other members of the LRR protein family. Southern blotting showed that lrrG was present in all GBS strains tested, representing the nine serotypes, and revealed the presence of an lrrG homologue in Streptococcus pyogenes. Recombinant LrrG protein was shown in vitro to adhere to epithelial cells in a dose-dependent manner, suggesting that it may function as an adhesion factor in GBS. More importantly, immunization with recombinant LrrG elicited a strong immunoglobulin G response in CBA/ca mice and protected against lethal challenge with virulent GBS. The data presented in this report suggest that this conserved protein is a highly promising candidate antigen for use in a GBS vaccine.     

Evolutionary genetic analysis of the emergence of epidemic Vibrio cholerae isolates on the basis of comparative nucleotide sequence analysis and multilocus virulence gene profiles

Vibrio cholerae, the causative agent of cholera, is a natural inhabitant of the aquatic ecosystem. We examined a unique collection of V. cholerae clinical and environmental isolates of widespread geographic distribution recovered over a 60-year period to determine their evolutionary genetic relationships based on analysis of two housekeeping genes, malate dehydrogenase (mdh) and a chaperonin (groEL). In addition, the phylogenetic distribution of 12 regions associated with virulence was determined. Comparative sequence analysis of mdh revealed that all V. cholerae O1 and O139 serogroup isolates belonged to the same clonal lineage. Single-strand conformational polymorphism (SSCP) analysis of these O1 and O139 strains at groEL confirmed the presence of an epidemic clonal complex. Of the 12 virulence regions examined, only three regions, Vibrio seventh pandemic island 1 (VSP-I), VSP-II, and RS1, were absent from all classical V. cholerae isolates. Most V. cholerae El Tor biotype and O139 serogroup isolates examined encoded all 12 virulence regions assayed. Outside of V. cholerae O1/O139 serogroup isolates, only one strain, VO7, contained VSP-I. Two V. cholerae El Tor isolates, GP155 and 2164-78, lacked both VSP-I and VSP-II, and one El Tor isolate, GP43, lacked VSP-II. Five non-O1/non-O139 serogroup isolates had an mdh sequence identical to that of the epidemic O1 and O139 strains. These isolates, similar to classical strains, lack both VSP-I and VSP-II. Four of the 12 virulence regions examined were found to be present in all isolates: hlyA, pilE, MSHA and RTX. Among non-O1/non-O139 isolates, however, the occurrence of the additional eight regions was considerably lower. The evolutionary relationships and multilocus virulence gene profiles of V. cholerae natural isolates indicate that consecutive pandemic strains arose from a common O1 serogroup progenitor through the successive acquisition of new virulence regions.