bluuebunny/crossref_metadata_2025 huggingface dataset:
In VivoFunctional Specificity and Homeostasis of Drosophila 14-3-3 Proteins
Authors: Acevedo Summer F , Tsigkari K Kirki , Grammenoudi Sofia , Skoulakis Efthimios M C
Published: July 2007

The functional specialization or redundancy of the ubiquitous 14-3-3 proteins constitutes a fundamental question in their biology and stems from their highly conserved structure and multiplicity of coexpressed isotypes. We address this question in vivo using mutations in the two Drosophila 14-3-3 genes, leonardo (14-3-3ζ) and D14-3-3ϵ. We demonstrate that D14-3-3ϵ is essential for embryonic hatching. Nevertheless, D14-3-3ϵ null homozygotes survive because they upregulate transcripts encoding the LEOII isoform at the time of hatching, compensating D14-3-3ϵ loss. This novel homeostatic response explains the reported functional redundancy of the Drosophila 14-3-3 isotypes and survival of D14-3-3ϵ mutants. The response appears unidirectional, as D14-3-3ϵ elevation upon LEO loss was not observed and elevation of leo transcripts was stage and tissue specific. In contrast, LEO levels are not changed in the wing disks, resulting in the aberrant wing veins characterizing D14-3-3ϵ mutants. Nevertheless, conditional overexpression of LEOI, but not of LEOII, in the wing disk can partially rescue the venation deficits. Thus, excess of a particular LEO isoform can functionally compensate for D14-3-3ϵ loss in a cellular-context-specific manner. These results demonstrate functional differences both among Drosophila 14-3-3 proteins and between the two LEO isoforms in vivo, which likely underlie differential dimer affinities toward 14-3-3 targets.
Alternative Splicing Gives Rise to Different Isoforms of the Neurospora crassa Tob55 Protein That Vary in Their Ability to Insert β-Barrel Proteins Into the Outer Mitochondrial Membrane
Authors: Hoppins Suzanne C , Go Nancy E , Klein Astrid , Schmitt Simone , Neupert Walter , Rapaport Doron , Nargang Frank E
Published: July 2007

Tob55 is the major component of the TOB complex, which is found in the outer membrane of mitochondria. A sheltered knockout of the tob55 gene was developed in Neurospora crassa. When grown under conditions that reduce the levels of the Tob55 protein, the strain exhibited a reduced growth rate and mitochondria isolated from these cells were deficient in their ability to import β-barrel proteins. Surprisingly, Western blots of wild-type mitochondrial proteins revealed two bands for Tob55 that differed by ∼4 kDa in their apparent molecular masses. Sequence analysis of cDNAs revealed that the tob55 mRNA is alternatively spliced and encodes three isoforms of the protein, which are predicted to contain 521, 516, or 483 amino acid residues. Mass spectrometry of proteins isolated from purified outer membrane vesicles confirmed the existence of each isoform in mitochondria. Strains that expressed each isoform of the protein individually were constructed. When cells expressing only the longest form of the protein were grown at elevated temperature, their growth rate was reduced and mitochondria isolated from these cells were deficient in their ability to assembly β-barrel proteins.
Cdc15 Is Required for Spore Morphogenesis Independently of Cdc14 in Saccharomyces cerevisiae
Authors: Pablo-Hernando M Evangelina , Arnaiz-Pita Yolanda , Nakanishi Hideki , Dawson Dean , del Rey Francisco , Neiman Aaron M , de Aldana Carlos R Vázquez
Published: July 2007

In Saccharomyces cerevisiae exit from mitosis requires the Cdc14 phosphatase to reverse CDK-mediated phosphorylation. Cdc14 is released from the nucleolus by the Cdc14 early anaphase release (FEAR) and mitotic exit network (MEN) pathways. In meiosis, the FEAR pathway is essential for exit from anaphase I. The MEN component Cdc15 is required for the formation of mature spores. To analyze the role of Cdc15 during sporulation, a conditional mutant in which CDC15 expression was controlled by the CLB2 promoter was used. Cdc15-depleted cells proceeded normally through the meiotic divisions but were unable to properly disassemble meiosis II spindles. The morphology of the prospore membrane was aberrant and failed to capture the nuclear lobes. Cdc15 was not required for Cdc14 release from the nucleoli, but it was essential to maintain Cdc14 released and for its nucleo-cytoplasmic transport. However, cells carrying a CDC14 allele with defects in nuclear export (Cdc14-ΔNES) were able to disassemble the spindle and to complete spore formation, suggesting that the Cdc14 nuclear export defect was not the cause of the phenotypes observed in cdc15 mutants.
A SAGA-Independent Function of SPT3 Mediates Transcriptional Deregulation in a Mutant of the Ccr4-Not Complex in Saccharomyces cerevisiae
Authors: James Nicole , Landrieux Emilie , Collart Martine A
Published: July 2007

The conserved multi-subunit Ccr4-Not complex regulates gene expression in diverse ways. In this work, we characterize the suppression of temperature sensitivity associated with a mutation in the gene encoding the scaffold subunit of the Ccr4-Not complex, NOT1, by the deletion of SPT3. We determine that the deletion of SPT3, but not the deletion of genes encoding other subunits of the SAGA complex, globally suppresses transcriptional defects of not1-2. We find that transcriptional activation in not1-2 is associated with increased binding of TFIID and SAGA at promoters of upregulated genes, and this is suppressed by the deletion of SPT3. Interestingly, Spt3p-dependent activation of transcription occurs in not1-2 even if the SAGA complex is disrupted by the deletion of SPT7 that encodes a subunit of SAGA required for its integrity. Consistent with a SAGA-independent function of Spt3p, the deletion of SPT3 displays synthetic phenotypes when combined with a deletion of SPT7. Taken together, our results provide a new view of the Spt3 protein by identifying a SAGA-independent function of this protein that is functionally linked to the Ccr4-Not complex.
Mms22 Preserves Genomic Integrity During DNA Replication in Schizosaccharomyces pombe
Authors: Dovey Claire L , Russell Paul
Published: July 2007

The faithful replication of the genome, coupled with the accurate repair of DNA damage, is essential for the maintenance of chromosomal integrity. The MMS22 gene of Saccharomyces cerevisiae plays an important but poorly understood role in preservation of genome integrity. Here we describe a novel gene in Schizosaccharomyces pombe that we propose is a highly diverged ortholog of MMS22. Fission yeast Mms22 functions in the recovery from replication-associated DNA damage. Loss of Mms22 results in the accumulation of spontaneous DNA damage in the S- and G2-phases of the cell cycle and elevated genomic instability. There are severe synthetic interactions involving mms22 and most of the homologous recombination proteins but not the structure-specific endonuclease Mus81-Eme1, which is required for survival of broken replication forks. Mms22 forms spontaneous nuclear foci and colocalizes with Rad22 in cells treated with camptothecin, suggesting that it has a direct role in repair of broken replication forks. Moreover, genetic interactions with components of the DNA replication fork suggest that Mms2 functions in the coordination of DNA synthesis following damage. We propose that Mms22 functions directly at the replication fork to maintain genomic integrity in a pathway involving Mus81-Eme1.
An Exact Sampling Formula for the Wright–Fisher Model and a Solution to a Conjecture About the Finite-Island Model
Authors: Lessard Sabin
Published: July 2007

An exact sampling formula for a Wright–Fisher population of fixed size N under the infinitely many neutral alleles model is deduced. This extends the Ewens formula for the configuration of a random sample to the case where the sample is drawn from a population of small size, that is, without the usual large-N and small-mutation-rate assumption. The formula is used to prove a conjecture ascertaining the validity of a diffusion approximation for the frequency of a mutant-type allele under weak selection in segregation with a wild-type allele in the limit finite-island model, namely, a population that is subdivided into a finite number of demes of size N and that receives an expected fraction m of migrants from a common migrant pool each generation, as the number of demes goes to infinity. This is done by applying the formula to the migrant ancestors of a single deme and sampling their types at random. The proof of the conjecture confirms an analogy between the island model and a random-mating population, but with a different timescale that has implications for estimation procedures.
High-Density Detection of Restriction-Site-Associated DNA Markers for Rapid Mapping of Mutated Loci in Neurospora
Authors: Lewis Zachary A , Shiver Anthony L , Stiffler Nicholas , Miller Michael R , Johnson Eric A , Selker Eric U
Published: July 2007

The wealth of sequence information available for Neurospora crassa and other fungi has greatly facilitated evolutionary and molecular analyses of this group. Although “reverse” genetics, in which genes are first identified by their sequence rather than by their mutant phenotypes, serves as a valuable new approach for elucidating biological processes, classical “forward” genetic analysis is still extremely useful. Unfortunately, mapping mutations and identifying the corresponding genes has typically been slow and laborious. To facilitate forward genetics in Neurospora, we have adapted microarray-based restriction-site-associated DNA (RAD) mapping for use with N. crassa oligonucleotide microarrays. This technique was used to simultaneously detect an unprecedented number of genomewide restriction site polymorphisms from two N. crassa strains: Mauriceville and Oak Ridge. Furthermore, RAD mapping was used to quickly map a previously unknown gene, defective in methylation-7 (dim-7).
Chondrodysplasia Punctata and Maternal Autoimmune Disease: A New Case and Review of the Literature
Authors: Shanske Alan L. , Bernstein Larry , Herzog Ronit
Published: August 2007

Classic rhizomelic chondrodysplasia punctata is a rare, autosomal, recessively inherited disorder that is characterized by proximal shortening of the limbs, punctuate calcifications of the epiphyses, cataracts, developmental delay, and early lethality. A distinctive biochemical profile is characteristic for each of the several defects of peroxisomal metabolism. Recently, cases have been described that were not associated with peroxisomal dysfunction. These cases were found to be secondary to teratogen exposure or maternal conditions. Since 1993, there have been 9 reported cases of neonates with rhizomelic chondrodysplasia punctata who were born to mothers with connective tissue disease. We followed a newborn boy with features suggestive of rhizomelic chondrodysplasia punctata whose biochemical studies failed to demonstrate a defect in either plasmalogen or cholesterol biosynthesis. His mother developed systemic lupus erythematosus 8 months after delivery. This case is compared with the previously reported 9 cases from the literature and is instructive in demonstrating a lesser known effect of maternal autoantibodies on the fetus.
Neurodevelopmental Outcome in Term Infants With Status Epilepticus Detected With Amplitude-Integrated Electroencephalography
Authors: van Rooij Linda G.M. , de Vries Linda S. , Handryastuti Setyo , Hawani Dewi , Groenendaal Floris , van Huffelen Alexander C. , Toet Mona C.
Published: August 2007

OBJECTIVES. This study evaluated seizure, patient characteristics, and neurodevelopmental outcome of term newborns with amplitude-integrated electroencephalography–detected status epilepticus.

METHODS. Fifty-six term infants with status epilepticus were identified during a 12.5-year period. The time of onset of status epilepticus, background pattern before and after status epilepticus, success of controlling status epilepticus with antiepileptic drugs, and neurodevelopmental outcome were studied.

RESULTS. The incidence of status epilepticus in our population was 18%. Forty-two infants (75%) had a poor outcome and 14 were normal at follow-up. When all infants were studied as a single group, we found that not the duration, but the background pattern was correlated with neurodevelopmental outcome. In 50% of the infants with a poor outcome, the background pattern was abnormal before the status epilepticus and in 71% after the status epilepticus. Among infants with a good outcome, background pattern was normal in 14% before and 7% after the status epilepticus. In a subgroup of 48 infants with hypoxic-ischemic encephalopathy, there was a significant difference in background pattern, as well as in duration of the status epilepticus between infants with a poor outcome, compared with those with a good outcome. In 48% of the infants with a poor outcome, the background pattern was abnormal before, and in 75% after the status epilepticus, compared with 25% and 13%, respectively, for those with a good outcome. In 57% of the infants with a hemorrhage or perinatal arterial stroke, the status epilepticus was not controlled with antiepileptic drugs, compared with 21% in infants with hypoxic-ischemic encephalopathy (not significant).

CONCLUSIONS. The background pattern at the onset of status epilepticus was the main predictor of neurodevelopmental outcome. The duration of the status epilepticus was only of predictive value in the infants with hypoxic-ischemic encephalopathy. No association was found between the ability to control status epilepticus and subsequent neurodevelopmental outcome.
Nonoperative Management of Spontaneous Splenic Rupture in Infectious Mononucleosis: A Case Report and Review of the Literature
Authors: Stephenson Jacob T. , DuBois Jeffrey J.
Published: August 2007

Spontaneous rupture of the spleen is a rare complication of infectious mononucleosis with no clear consensus on appropriate management. Although management of traumatic splenic rupture has largely moved to nonoperative treatment, splenectomy is still frequently used in dealing with rupture of the diseased spleen. Here we report the case of a 16-year-old boy with splenic rupture secondary to laboratory-confirmed infectious mononucleosis in the absence of trauma. Nonoperative management including ICU admission, serial computed tomography scans, and activity limitation was used successfully. Our experience, along with a review of the literature, leads us to conclude that splenic preservation can be a safe alternative to splenectomy in hemodynamically stable patients with spontaneous splenic rupture. This is of particular importance in the pediatric population, which is at higher risk for postsplenectomy sepsis.
Metabolic Correction Induced by Leptin Replacement Treatment in Young Children With Berardinelli-Seip Congenital Lipoatrophy
Authors: Beltrand Jacques , Beregszaszi Marta , Chevenne Didier , Sebag Guy , De Kerdanet Marc , Huet Frédéric , Polak Michel , Tubiana-Rufi Nadia , Lacombe Didier , De Paoli Alex M. , Levy-Marchal Claire
Published: August 2007

OBJECTIVE. Berardinelli-Seip syndrome is a rare congenital lipoatrophy with a severe prognosis and no efficient therapy. Children present with low leptin levels and severe metabolic complications (insulin resistance, elevated triglyceride levels, and hepatic steatosis). The objective of this study was to test safety and efficacy of recombinant-methionyl-human leptin replacement in children with Berardinelli-Seip syndrome before development of severe metabolic disease

METHODS. As part of an open trial, recombinant-methionyl-human leptin was given daily for 4 months to children who did not have diabetes and had Berardinelli-Seip congenital lipoatrophy and metabolic complications at a dosage that was meant to achieve physiologic levels. Six boys and 1 girl (age: 2.4–13.6 years), with a mean fasting insulin level of >15 mIU/L and hypertriglyceridemia, were included.

RESULTS. At the end of the recombinant-methionyl-human leptin treatment, a 63% reduction of fasting triglycerides level was achieved. A simultaneous 30% increase in insulin sensitivity was seen, and liver volume was reduced by 20.3%. More remarkable, values of insulin sensitivity and triglyceride level were in the reference range in 4 patients.

CONCLUSIONS. Leptin replacement is able to reverse metabolic complications in the majority of children with Berardinelli-Seip congenital lipoatrophy and with insulin resistance or dyslipidemia before the development of overt diabetes.
Myocardial Infarction in an Adolescent: Anomalous Origin of the Left Main Coronary Artery From the Right Coronary Sinus in Association With Combined Prothrombotic Defects
Authors: Koestenberger Martin , Nagel Bert , Gamillscheg Andreas , Temmel Werner , Cvirn Gerhard , Beitzke Albrecht
Published: August 2007

We present the case of a 15-year-old boy with clinical features of an acute myocardial infarction. Angiography revealed a complete obstruction of the left main coronary artery. A coronary-aorto-bypass graft was undertaken immediately. Cardiac computed tomography demonstrated an anomalous origin of the left main coronary artery from the right coronary sinus of the aorta. A thrombophilic state with a heterozygote genotype for prothrombin G20210 mutation, a C677T methylenetetrahydrofolate reductase gene mutation, and a protein C type 1 deficiency was detected. No other embolic source could be identified. The patient recovered with persistent left ventricular dysfunction. He is now taking the anticoagulant warfarin. Combined prothrombotic defects in combination with additional risk factors such as coronary anomalies can lead to myocardial infarction even in children and adolescents.
Cytokine Profiles in the Respiratory Tract During Primary Infection With Human Metapneumovirus, Respiratory Syncytial Virus, or Influenza Virus in Infants
Authors: Melendi Guillermina A. , Laham Federico R. , Monsalvo A. Clara , Casellas Javier M. , Israele Victor , Polack Norberto R. , Kleeberger Steven R. , Polack Fernando P.
Published: August 2007

OBJECTIVES. We characterized the T helper cytokine profiles in the respiratory tract of infants infected with influenza virus, human metapneumovirus, and respiratory syncytial virus to examine whether these agents elicit similar cytokine responses and whether T helper type 2 polarization is associated with wheezing and severe disease.

METHODS. A prospective study of infants who were seeking medical help for acute upper and/or lower respiratory tract infection symptoms for the first time and were found to be infected with influenza, human metapneumovirus, or respiratory syncytial virus was performed. Respiratory viruses were detected in nasal secretions with reverse transcriptase-polymerase chain reaction assays. The study was performed in emergency departments and outpatient clinics in Buenos Aires, Argentina. T cell cytokine responses were determined in nasal secretions with immunoassays and reverse transcriptase-polymerase chain reaction assays.

RESULTS. Influenza elicited higher levels of interferon-γ, interleukin-4, and interleukin-2 than did the other agents. Human metapneumovirus had the lowest interferon-γ/interleukin-4 ratio (T helper type 2 bias). However, no association was found between T helper type 2 bias and overall wheezing or hospitalization rates.

CONCLUSIONS. These findings show that viral respiratory infections in infants elicit different cytokine responses and that the pathogeneses of these agents should be studied individually.
Contact With Farm Animals in Early Life and Juvenile Inflammatory Bowel Disease: A Case-Control Study
Authors: Radon Katja , Windstetter Doris , Poluda Anna Laura , Mueller Beatrice , Mutius Erika von , Koletzko Sibylle ,   Chronische Autoimmunerkrankungen und Kontakt zu Tieren (Chronic Autoimmune Disease and Animal Contact) Study Group
Published: August 2007

OBJECTIVE. The aim of this study was to test the association between farm animal contact in infancy and the development of juvenile Crohn disease and ulcerative colitis.

METHODS. A case-control study was conducted in 13 children's hospitals by using a mailed questionnaire. Case subjects with Crohn disease or ulcerative colitis who were registered in these hospitals were eligible (response rate: 90%). Children who underwent strabismus surgery at 11 of the 13 centers served as control subjects (response rate: 85%). All children 6 to 18 years of age who were born in Germany without malformations were included (444 case subjects with Crohn disease, 304 case subjects with ulcerative colitis, and 1481 control subjects).

RESULTS. Regular contact with farm animals during the first year of life was associated inversely with Crohn disease and ulcerative colitis. In addition, regular contact with cats in infancy was linked inversely with case status. Allergic rhinitis was correlated significantly with Crohn disease but not with ulcerative colitis.

CONCLUSION. Contact with farm environments in infancy might decrease the risk of juvenile Crohn disease and ulcerative colitis.
Functional Impairment of the Brainstem in Infants With Bronchopulmonary Dysplasia
Authors: Wilkinson Andrew R. , Brosi Dorothea M. , Jiang Ze D.
Published: August 2007

OBJECTIVES. To gain new insights into the influence of bronchopulmonary dysplasia on the immature brain and to detect abnormalities, we studied the functional integrity of the brainstem in infants with bronchopulmonary dysplasia.

METHODS. Forty-one very preterm infants with bronchopulmonary dysplasia were studied at postconceptional ages of 37 to 42 weeks. Brainstem auditory evoked responses were recorded and analyzed by using the maximal length sequence technique.

RESULTS. Compared with term control subjects, wave V latency in the maximal length sequence brainstem auditory evoked response of the infants with bronchopulmonary dysplasia increased significantly at all 91 to 910 clicks per second rates. Similarly, I–V and particularly III–V interpeak intervals increased significantly. The III–V/I–III interval ratio also increased significantly at all click rates. All of these abnormalities became more significant as the click rate was increased. Compared with healthy, very preterm control subjects, all of these maximal length sequence brainstem auditory evoked response variables increased significantly at all click rates, although the differences between the 2 groups were slightly smaller than those between the infants with bronchopulmonary dysplasia and the term control subjects. The wave I and III latencies and I–III interval in the infants with bronchopulmonary dysplasia did not show any abnormalities. The slopes of the wave V latency-rate function and I–V and particularly III–V interval-rate functions for the infants with bronchopulmonary dysplasia were significantly steeper than those for both term and healthy, very preterm control subjects. The slope of the III–V/I–III interval ratio-rate function for the infants with bronchopulmonary dysplasia was also significantly steeper than those for the 2 control groups.

CONCLUSIONS. The results suggest poor myelination and synaptic function of the brainstem in infants with bronchopulmonary dysplasia, resulting in impaired functional integrity. In comparison, peripheral neural function was relatively intact.
Risk of Serious Neurologic Disease After Immunization of Young Children in Britain and Ireland
Authors: Ward Katherine N. , Bryant Naomi J. , Andrews Nick J. , Bowley Jennifer S. , Ohrling Anu , Verity Christopher M. , Ross Euan M. , Miller Elizabeth
Published: August 2007

OBJECTIVE. We sought to investigate the risk of serious neurologic disease after immunization in early childhood.

METHODS. The results of a 3-year prospective study of children (2–35 months old) in Britain and Ireland with encephalitis and/or severe illness with convulsions and fever were linked to each child's vaccine history. Cases were reported via the British Paediatric Surveillance Unit's network. The self-controlled case-series method was used to investigate associations between immunization and acute potential adverse events. The risk periods investigated were 0 to 3 and 0 to 7 days post–diphtheria, tetanus, whole cell pertussis, Haemophilus influenzae type b or meningococcal C conjugate vaccine and 6 to 11 and 15 to 35 days post–measles, mumps, rubella vaccine.

RESULTS. A total of 157 disease episodes from 155 children met the analytical case definition. There were 11 cases of herpes simplex encephalitis and 23 cases of primary human herpesvirus 6 and/or 7 infection. There was no evidence of a raised relative incidence of serious neurologic disease in any of the specified risk periods with the exception of a raised relative incidence of 5.68 in the 6–11 days after measles, mumps, rubella vaccine. Based on this relative incidence, between 3 and 6 of the 6 cases in this period were estimated to be attributable to the vaccine with a best estimate of 5. The 6 cases all had fever with convulsions lasting >30 minutes; in all but 1, there was complete recovery by discharge from hospital. Of the 5 patients who recovered, 1 had a concurrent primary human herpesvirus 6 infection and one a primary human herpesvirus 7.

CONCLUSIONS. Six to 11 days after measles, mumps, rubella vaccine there is an increased risk of fever and convulsions lasting >30 minutes. All 6 of the episodes temporally related to immunization met the criteria for complex febrile convulsions. The estimated attributable risk of serious neurological disease was similar to that previously found for measles vaccine.
Cost-effectiveness of Head Computed Tomography in Infants With Possible Inflicted Traumatic Brain Injury
Authors: Campbell Kristine A. , Berger Rachel P. , Ettaro Lorraine , Roberts Mark S.
Published: August 2007

OBJECTIVE. Early diagnosis of inflicted traumatic brain injury may reduce morbidity and mortality associated with repeated inflicted traumatic brain injuries. We undertook this study to estimate the cost-effectiveness of a policy of head computed tomography (CT) for inflicted traumatic brain injury in selected infants seen in an emergency department.

METHODS. We constructed Markov models to compare a policy of CT to no CT in an asymptomatic 5-week-old infant with either (1) unexplained scalp bruising or (2) a history of an apparent life-threatening event. Health states modeled were no inflicted traumatic brain injury, misdiagnosed inflicted traumatic brain injury, mild inflicted traumatic brain injury (diagnosed or undiagnosed), and severe and fatal inflicted traumatic brain injury. Infants with undiagnosed inflicted traumatic brain injury were at increased risk of repeat inflicted traumatic brain injury. We used available literature to estimate probabilities, costs, and outcomes. The models terminated at death or at 52 weeks of age. Outcomes considered were severe and fatal inflicted traumatic brain injury cases averted through early detection of mild inflicted traumatic brain injury.

DATA SOURCES. We conducted a literature review for estimates of inflicted traumatic brain injury incidence, outcome probabilities, and medical and societal costs. Wide ranges were set for sensitivity and Monte Carlo analyses.

RESULTS. From a medical payer perspective, head CT for inflicted traumatic brain injury in infants with unexplained scalp bruising saved money. Sensitivity analysis demonstrated costs less than $50000 per severe or fatal inflicted traumatic brain injury averted in scenarios in which initial inflicted traumatic brain injury prevalence was >3%. From a societal perspective, costs of child protection made head CT for inflicted traumatic brain injury more expensive.

CONCLUSIONS. From a medical payer perspective, our models demonstrate that CT for inflicted traumatic brain injury can be cost-effective and improve outcomes. The finding of higher societal cost reflects the substantial short-term costs of child protection. Our study supports a low medical threshold for CT screening and highlights the need for improved understanding of long-term costs and outcomes of child abuse.
Peripheral Dentinogenic Ghost Cell Tumor of the Gingiva
Authors: Iezzi Giovanna , Rubini Corrado , Fioroni Massimiliano , Piattelli Adriano
Published: August 2007

Background: A dentinogenic ghost cell tumor is a locally invasive neoplasm that is characterized by ameloblastoma‐like islands of epithelial cells in a mature connective tissue stroma.

Methods: A 43‐year‐old male patient presented a well‐circumscribed sessile, exophytic mass of the gingiva with a diameter of 2 cm located in the canine area of the right maxilla. The lesion was enucleated.

Results: The lesion showed odontogenic epithelium, ghost cells, dentinoid material, and giant cells. The final microscopic diagnosis was a dentinogenic ghost cell tumor.

Conclusions: A dentinogenic ghost cell tumor is an extremely rare tumor, and only a few cases have been reported in the English literature. The peripheral, extraosseous lesion can be easily confused with other gingival lesions such as reactive or inflammatory lesions or other peripheral odontogenic tumors. The clinical appearance of all of these lesions is similar; therefore, the definitive diagnosis depends on histology, and a biopsy with a microscopic examination is mandatory.
Comparative Efficacy of Stabilized Stannous Fluoride/Sodium Hexametaphosphate Dentifrice and Sodium Fluoride/Triclosan/Copolymer Dentifrice for the Prevention of Periodontitis in Xerostomic Patients: A 2‐Year Randomized Clinical Trial
Authors: Papas Athena , He Tao , Martuscelli Gianluca , Singh Mabi , Bartizek Robert D. , Biesbrock Aaron R.
Published: August 2007

Background: The primary objective of this study was to compare the efficacy of a stannous fluoride (SnF2) dentifrice relative to a positive control triclosan dentifrice for prevention of clinical attachment loss (CAL) in xerostomic patients. A secondary objective was to compare the dentifrices for root caries remineralization.

Methods: This was a 2‐year, randomized, double‐masked, parallel‐group study. A 0.454% SnF2/sodium hexametaphosphate dentifrice was tested versus a positive control dentifrice (sodium fluoride/0.30% triclosan/copolymer) in 440 medication‐induced xerostomic adults identified in a 1‐year, run‐in phase (no treatment) as high risk for periodontitis and root caries. During the study phase, subjects were stratified based on gender and attachment level into two groups. Subjects brushed twice a day for 60 seconds using their assigned product. Clinical examinations including probing depth, attachment level, bleeding on probing, and root caries remineralization were performed at baseline and 1 and 2 years.

Results: A total of 334 subjects were evaluable. During run‐in, average CAL relative to initial examination was 1.33 mm. Probing depth increased 0.95 mm. At year 2 in the treatment phase, attachment gain was 0.77 mm for the test group and 0.79 mm for the control group versus baseline. Probing depth decreased 0.57 mm for the test group, similar to the control group (0.53 mm). These changes versus baseline were statistically significant (P <0.01) for each group. Products were not statistically significantly different from each other. Both treatments resulted in similar remineralization for root caries lesions at study completion (P = 0.40).

Conclusion: The results establish comparable benefits for the SnF2 dentifrice in preventing CAL and root caries versus the sodium fluoride/triclosan/copolymer control in xerostomic patients.
Effect of Simvastatin Administration on Periodontitis‐Associated Bone Loss in Ovariectomized Rats
Authors: Vaziri Hamed , Naserhojjati‐Roodsari Reza , Tahsili‐Fahadan Nima , Khojasteh Arash , Mashhadi‐Abbas Fatemeh , Eslami Behnam , Dehpour Ahmad Reza
Published: August 2007

Background: Hydroxyl methylglutaryl‐coenzyme A reductase inhibitors, so‐called statins, have been widely used for hyperlipidemic patients. Recently, it has been reported that they promote bone formation. The purpose of this study was to evaluate the effect of simvastatin on ligature‐induced bone resorption in the mandible of the ovariectomized rat.

Methods: Forty‐nine rats were divided into seven groups; ligature was placed in all groups except group 7, which was considered the sham group: group 1 (N = 7), ovariectomy (OVX) plus simvastatin (10−6 M); group 2 (N = 7), OVX plus simvastatin (3 × 10−7 M); group 3 (N = 7), OVX plus simvastatin (10−7 M); group 4 (N = 7), OVX plus normal saline; group 5 (N = 7), OVX group; group 6 (N = 7), ligature without OVX; and group 7 (N = 7), sham surgery without OVX and ligature. Simvastatin was administered subperiosteally in the buccal fold of the bottom right first molar twice a week during the study. Four weeks after insertion of the ligatures, the animals were sacrificed. Mandibles were removed for radiologic and histologic analysis. Bone density, bone loss (BL), and attachment loss were measured. Analysis of variance (ANOVA) was used to compare groups.

Results: Histologic analysis showed that the simvastatin groups developed significantly less periodontal breakdown (P <0.05). BL was less in the simvastatin experimental group, but there was not a significant statistical difference between the simvastatin groups (groups 1 through 3) and the experimental control groups (groups 5 and 6; P >0.05).

Conclusion: Within the limits of this study, it can be concluded that simvastatin shows protective features against the impact of periodontitis on attachment apparatus and alveolar bone.
Topical Use of a Metronidazole Gel in the Treatment of Sites With Symptoms of Recurring Chronic Inflammation
Authors: Leiknes Tom , Leknes Knut N. , Böe Olav E. , Skavland Ragnfrid J. , Lie Tryggve
Published: August 2007

Background: Bacterial plaque accumulation at the dentogingival junction and in periodontal pockets is the major etiologic factor in all manifestations of periodontal disease. The aim of this study was to evaluate whether a locally delivered 25% metronidazole gel after scaling and root planing (SRP) would enhance the treatment outcome over SRP alone in periodontal pockets with symptoms of recurring chronic inflammation.

Methods: Twenty‐one maintenance‐care patients, 10 men and 11 women, having at least one pair of contralateral anatomically matching proximal tooth surfaces showing probing depth ≥5 mm and bleeding on probing (BOP), were included in the study. The sites were randomized to be treated with SRP plus 25% metronidazole gel (test sites) or with SRP alone (control sites) in a split‐mouth design. Clinical evaluations were performed immediately pretreatment (baseline) and at 3 and 6 months post‐treatment.

Results: Both treatments yielded a statistically significant (P = 0.001) reduction in probing depth (1.9 and 1.8 mm), gain of attachment level (1.6 and 1.0 mm), and reduction of BOP (38.1% and 33.3%) for test and control sites, respectively, at 6 months. There was no statistically significant difference between the treatments for any of the clinical parameters.

Conclusion: This study indicates that a locally applied 25% metronidazole gel does not improve the treatment outcome over SRP alone in sites with recurring chronic inflammation in maintenance‐care patients.
Subantimicrobial Dose Doxycycline Effects on Osteopenic Bone Loss: Microbiologic Results
Authors: Walker Clay , Puumala Susan , Golub Lorne M. , Stoner Julie A. , Reinhardt Richard A. , Lee Hsi‐Ming , Payne Jeffrey B.
Published: August 2007

Background: Based on microbiologic concerns, the safety of a 24‐month regimen of subantimicrobial dose doxycycline (SDD; 20 mg twice a day) was evaluated in postmenopausal osteopenic women with periodontitis in a double‐blind, placebo‐controlled, randomized clinical trial.

Methods: Subgingival samples were collected from two sites (probing depth ≥5 mm) in each of 128 subjects at baseline, with the same sites resampled at the conclusion of the 2‐year period. The samples were enumerated on selective and non‐selective media and on doxycycline (4 μg/ml) medium. Up to five different colonial morphologies were subcultured from the doxycycline medium, identified to species, and susceptibilities determined to doxycycline and five other antibiotics. Data were analyzed for microbial differences in total colony forming units (CFU), periodontal and opportunistic pathogens, and changes in species and in susceptibilities of isolates recovered on doxycycline medium.

Results: There was no significant evidence that changes in total anaerobic counts over the treatment period (P = 0.96) differed between treatment groups. Likewise, periodontal pathogens, opportunistic pathogens, or normal flora did not differ descriptively between groups. Although there was a significant increase (P <0.001) in the total CFU recovered from the 4 μg/ml doxycycline plates at 24 months for SDD versus placebo, the percentage that was clinically resistant to doxycycline (minimal inhibitory concentration [MIC] ≥16 μg/ml) decreased over the 24‐month period in both groups and did not differ between the treatment groups (SDD: 79% to 76%; placebo: 83% to 70%; P = 0.2). There were no significant differences (P >0.28 for each) in the change in cross‐resistance between the groups for doxycycline and the other five antibiotics.

Conclusions: No antimicrobial effect on the subgingival flora was detected following treatment with SDD for 24 months, relative to baseline or to placebo. The increase in initial resistance (at 4 μg/ml) did not translate into a significant increase in the percent resistant to doxycycline (MIC ≥16 μg/ml) for patients in the SDD group.
Effects of Glass Ionomer and Microfilled Composite Subgingival Restorations on Periodontal Tissue and Subgingival Biofilm: A 6‐Month Evaluation
Authors: Santos Vanessa Renata , Lucchesi Juliana Antico , Cortelli Sheila Cavalca , Amaral Cristiane Mariote , Feres Magda , Duarte Poliana Mendes
Published: August 2007

Background: This 6‐month study evaluated the effects of resin‐modified glass‐ionomer cement (RMGI) and microfilled composite (MC) subgingival restorations on periodontal tissues and subgingival biofilm.

Methods: Fifty‐four periodontally healthy patients were assigned as follows: group 1 (N = 18), root exposure (RE) without non‐carious cervical lesions (NCCL) treated with coronally positioned flap (CPF); group 2 (N = 18), RE with NCCL treated RMGI restorations plus CPF; group 3 (N = 18), RE with NCCL treated with MC restorations plus CPF. Probing depth (PD), visible local plaque score (PL), and local bleeding on probing (BOP) were assessed at baseline and 6 months after surgeries. Restored and non‐restored root recoverage (RR) was assessed at 6 months. Each experimental tooth was subgingivally sampled (baseline and 6 months) and analyzed by checkerboard DNA‐DNA hybridization.

Results: Clinical results showed no significant differences among the groups regarding PL, BOP, and PD at baseline and 6 months. The RR means were similar among the groups at 6 months. Intragroup analyses revealed that the proportions of 10 periodontopathogens decreased at 6 months for the control group. For the RMGI group, there was a significant decrease in the proportions of nine periodontopathogens. For the MC group, there was a significant increase in the proportions of Fusobacterium nucleatum polymorphum and Gemella morbillorum and a decrease in five periodontopathogens. Intergroup analyses showed an increase in the proportion of F. nucleatum polymorphum for the MC group.

Conclusions: In a 6‐month evaluation, well‐finished RMGI or MC subgingival restorations did not negatively affect periodontal health. Furthermore, RMGI seems to exert more positive effects on the subgingival biofilm composition than MC.
Gingival Epithelial Cell Expression of Macrophage Inflammatory Protein‐1α Induced by Interleukin‐1β and Lipopolysaccharide
Authors: Ryu Ok H. , Choi Sun J. , Linares Ana Maria G. , Song In S. , Kim Young J. , Jang Ki T. , Hart Thomas C.
Published: August 2007

Background: Elevated levels of the macrophage inflammatory protein‐1α (MIP‐1α) are reported in inflammatory bone diseases including periodontitis. We evaluated the ability of interleukin‐1β (IL‐1β) and bacterial lipopolysaccharides (LPSs) to modulate MIP‐1α expression in epithelial cells, fibroblasts, and polymorphonuclear leukocytes (PMNs). We also evaluated the effect of MIP‐1α as an osteoclast activating factor.

Methods: Human gingival epithelial cells and fibroblasts were obtained by primary cell culture. PMNs were isolated from healthy controls. Human MG63 osteosarcoma cells were used as osteoblastic cells. After incubation of each cell type with IL‐1β, Porphyromonas gingivalis LPS, and Actinobacillus actinomycetemcomitans LPS, MIP‐1α mRNA and secreted protein levels were quantified by reverse transcription‐polymerase chain reaction, enzyme‐linked immunosorbent assay, and immunohistochemistry. The ability of recombinant MIP‐1α to induce osteoclast formation was determined by tartrate resistant acid phosphatase assay.

Results: MIP‐1α expression in PMNs and gingival epithelial cells was induced by IL‐1β and LPS, but neither induced MIP‐1α expression in gingival fibroblasts or osteoblastic cells. MIP‐1α was highly expressed in the basal epithelial layer of inflamed gingiva but not in healthy gingiva. MIP‐1α induced osteoclast formation at an optimal concentration of 0.05 to 2 ng/ml.

Conclusions: MIP‐1α expression by gingival epithelial cells may be important in initiating inflammation by facilitating accumulation and activation of leukocytes. The ability of MIP‐1α to facilitate formation of multinuclear bone cells indicates a possible role in periodontitis‐associated bone destruction. These findings indicate MIP‐1α may play an important role in early and later stages of inflammatory‐related periodontitis.
Pharmacological and Chemical Effects of Cigarette Additives
Authors: Rabinoff Michael , Caskey Nicholas , Rissling Anthony , Park Candice
Published: August 2007

We investigated tobacco industry documents and other sources for evidence of possible pharmacological and chemical effects of tobacco additives.

Our findings indicated that more than 100 of 599 documented cigarette additives have pharmacological actions that camouflage the odor of environmental tobacco smoke emitted from cigarettes, enhance or maintain nicotine delivery, could increase the addictiveness of cigarettes, and mask symptoms and illnesses associated with smoking behaviors.

Whether such uses were specifically intended for these agents is unknown. Our results provide a clear rationale for regulatory control of tobacco additives.
Low-Income Employees’ Choices Regarding Employment Benefits Aimed at Improving the Socioeconomic Determinants of Health
Authors: Danis Marion , Lovett Francis , Sabik Lindsay , Adikes Katherin , Cheng Glen , Aomo Tom
Published: August 2007

Objectives. Socioeconomic factors are associated with reduced health status in low-income populations. We sought to identify affordable employment benefit packages that might ameliorate these socioeconomic factors and would be consonant with employees’ priorities.

Methods. Working in groups (n = 53), low-income employees (n = 408; 62% women, 65% Black) from the Washington, DC, and Baltimore, Md, metropolitan area, participated in a computerized exercise in which they expressed their preference for employment benefit packages intended to address socioeconomic determinants of health. The hypothetical costs of these benefits reflected those of the average US benefit package available to low-income employees. Questionnaires ascertained sociodemographic information and attitudes. Descriptive statistics and logistic regression analysis were used to examine benefit choices.

Results. Groups chose offered benefits in the following descending rank order: health care, retirement, vacation, disability pay, training, job flexibility, family time, dependent care, monetary advice, anxiety assistance, wellness, housing assistance, and nutrition programs. Participants varied in their personal choices, but 78% expressed willingness to abide by their groups’ choices.

Conclusions. It is possible to design employment benefits that ameliorate socioeconomic determinants of health and are acceptable to low-income employees. These benefit packages can be provided at the cost of benefit packages currently available to some low-income employees.
Associations Between Sociodemographics and Safety Belt Use in States With and Without Primary Enforcement Laws
Authors: Beck Laurie F. , Shults Ruth A. , Mack Karin A. , Ryan George W.
Published: August 2007

Objectives.secondary enforcement laws (police may issue a safety belt citation only if the vehicle has been stopped for another reason).

Methods. We analyzed 2002 Behavioral Risk Factor Surveillance System data from 50 states and the District of Columbia. We performed multivariable, log-linear regression analyses to assess the effect of sociodemographic characteristics and safety belt laws on safety belt use. Analyses were stratified by the type of enforcement permitted by state laws.

Results. Reported safety belt use was higher in states that had primary versus secondary enforcement laws, both overall and for each sociodemographic characteristic examined. Safety belt use was 85% in states that had primary enforcement laws and 74% in states that had secondary enforcement laws. Cross-sectional data suggested that primary enforcement laws may have the greatest effect on sociodemographic groups that reported lower levels of safety belt use.

Conclusions. Primary enforcement laws are an effective population-based strategy for reducing disparities in safety belt use and may, therefore, reduce disparities in crash-related injuries and fatalities.
The Effect on Ecological Systems of Remediation to Protect Human Health
Authors: Burger Joanna
Published: August 2007

Environmental remediation of contaminated eco-sytems reduces stresses to these ecosystems, including stresses caused by the production, use, and storage of weapons of mass destruction. The effects of these various stressors on humans can be reduced by remediation or by blocking the exposure of humans, but blocking the exposure of resident biota is almost impossible.

Remediation may involve trade-offs between reducing a minor risk to public health and increasing risks to workers and ecosystems. Remediation practices such as soil removal disrupt ecosystems, which take decades to recover. Without further human disturbances, and with low levels of exposure to stress-ors, ecosystems can recover from physical disruptions and spills.

Remediation to remove negligible risk to humans can destroy delicate ecosystems for very little gain in public health.
The Prophylactic Extraction of Third Molars: A Public Health Hazard
Authors: Friedman Jay W.
Published: August 2007

Ten million third molars (wisdom teeth) are extracted from approximately 5 million people in the United States each year at an annual cost of over $3 billion.

In addition, more than 11 million patient days of “standard discomfort or disability”—pain, swelling, bruising, and malaise—result postoperatively, and more than 11000 people suffer permanent paresthesia—numbness of the lip, tongue, and cheek—as a consequence of nerve injury during the surgery. At least two thirds of these extractions, associated costs, and injuries are unnecessary, constituting a silent epidemic of iatrogenic injury that afflicts tens of thousands of people with lifelong discomfort and disability.

Avoidance of prophylactic extraction of third molars can prevent this public health hazard.
State Health Policy for Terrorism Preparedness
Authors: Ziskin Leah Z. , Harris Drew A.
Published: August 2007

State health policy for terrorism preparedness began before the terrorist attacks on September 11, 2001, but was accelerated after that day. In a crisis atmosphere after September 11, the states found their policies changing rapidly, greatly influenced by federal policies and federal dollars. In the 5 years since September 11, these state health policies have been refined. This refinement has included a restatement of the goals and objectives of state programs, the modernization of emergency powers statutes, the education and training of the public health workforce, and a preparation of the health care system to better care for victims of disasters, including acts of terrorism.