Perceived value of providing peer reviewers with abstracts and preprints of related published and unpublished papers.

CONTEXT: Many journals provide peer reviewers with written instructions regarding review criteria, such as the originality of results, but little research has been done to investigate ways to improve or facilitate the peer review task. OBJECTIVE: To assess the value that peer reviewers place on receipt of supplemental materials (eg, abstracts of related papers and preprints of related unpublished manuscripts). DESIGN: Questionnaire survey sent to all 733 peer reviewers recruited by the Journal of the National Cancer Institute to review 356 manuscripts consecutively sent out for review from February 24, 1997, through January 16, 1998. The inclusion of supplemental materials with manuscript review packages was optional. MAIN OUTCOME MEASURE: The peer reviewers' assessment of the actual or potential usefulness of supplemental materials on the performance of peer review. RESULTS: A total of 481 (66%) of 733 questionnaires were returned. Of the 471 respondents' questionnaires that could be used, 217 (46%) indicated that they received abstracts, and 44 (10%) of 458 respondents indicated that they received preprints. Higher proportions of peer reviewers who received supplemental materials than those who had not received them felt that they were (or would be) useful to them when reviewing the manuscript (63% [95% confidence interval (CI), 57%-69%] vs 45% [95% CI, 38%-52%]; P<.001) and to the peer review process in general (80% [95% CI, 75%-85%] vs 64% [95% CI, 58%-70%]; P<.001). CONCLUSION: The majority of respondents indicated that supplemental materials helped (or would have helped) them evaluate manuscripts and valued them more highly when they actually received them.

Pharmacology of the pulmonary diseases.

The management of patients with pulmonary diseases may pose a challenge to the dentist. A thorough understanding of the major respiratory diseases is paramount to the successful treatment of these individuals. Morbidity and mortality for COPD patients have increased over time. There has been a decline in the number of smokers in the United States, but it may take two or three decades before health care systems notice a decrease in associated health care visits. Smoking tobacco is the major cause of COPD. Health care providers need to inform patients about smoking cessation programs and motivate them toward that end. The most important factor in preventing COPD is helping patients stop smoking. Mainstays in the treatment of COPD include inhaled anticholinergics and supplemental oxygen, when indicated. For certain patients, beta2-agonists, mucolytics, anti-inflammatory agents, and antibiotics are indicated. Asthma morbidity and mortality continue to rise significantly despite scientific advances and improved understanding of the disease and ability to render effective treatment. The reasons for this are not entirely clear. Asthma treatment has been revolutionized over the past decade. If proper preventive environmental measures and medications are prescribed, and the patients are carefully educated and complaint, their prognosis is good, and their condition should rarely require emergency treatment or hospitalization. The management of TB in the dental office involves several aspects of the disease. The dentist should be able to refer properly a patient with signs and symptoms of disease or to follow up on inadequate treatment. The medications taken for TB do not usually modify the dental management of the patient. The complications of the medications may, however, affect some drugs the dentist could prescribe. The resurgence of TB in the United States mandates that every dentist understand this disease and its importance.

An upstream region of the H2AZ gene promoter modulates promoter activity in different cell types.

Human H2AZ gene promoter fragments that included sequences upstream from the core promoter resulted in decreased activity of reporter constructs transfected into several human cell lines, but increased activity in the undifferentiated human embryonal carcinoma cell line Tera-2. Differentiation of Tera-2 cells in media containing retinoic acid restored the ability of the upstream region to downregulate H2AZ gene promoter activity. Levels of endogenous H2AZ mRNA were also found to be 2.5-fold higher in undifferentiated Tera-2 cells than in differentiated Tera-2 cells. A 128 bp region located 234 to 361 bp upstream from the transcription start site of the H2AZ gene was found to be responsible for the modulation of reporter activity. The upstream region also functioned similarly when removed from the H2AZ gene promoter and inserted upstream of the SV40 promoter in reporter constructs. Gel mobility shift studies of fragments of this region revealed two sequence elements, CTCCTCC and CACGTG, that bound nuclear factors in vitro.

Characterization of the proximal promoter of the human histone H2A.Z gene.

Histone H2A.Z is a distinct and evolutionarily conserved member of the histone H2A family whose synthesis, in contrast to that of most other histone species, is not dependent on DNA replication. The gene for H2A.Z lacks the signals involved in the 3' processing of replication-linked histone mRNA species and contains introns as well as polyadenylation signals. The H2A.Z gene proximal promoter, a 200-bp region upstream of the transcription start site that provides maximal activity in CAT reporter studies, contains three CCAAT and two GGGCGG elements as well as a consensus TATA element. In vitro DNase I footprint analysis of this region indicated that the central CCAAT and the distal GGGCGG elements were protected by factors present in HeLa nuclear extract. Site-directed mutations of selected promoter elements were generated in the H2A.Z gene promoter region of a CAT reporter construct by a novel one-step PCR procedure. Of the elements examined, the central CCAAT element was found to be the most important determinant of promoter activity; its disruption decreased CAT reporter activity by 65%. Disruption of the proximal CCAAT or the distal GGGCGG elements led to decreases in activity of 40%, while disruption of any of the other examined led to smaller decreases. Gel-mobility shift analysis showed that the three CCAAT elements had overlapping but not identical binding specificities for nuclear factors. The two GGGCGG elements both were found to bind transcription factor Sp1, but the distal element bound Sp1 with higher affinity. The findings show that the central and proximal CCAAT elements and the distal GGGCGG element appear to be the major determinants of the transcriptional activity of the H2A.Z gene.

Characterization of the human histone H2A.X gene. Comparison of its promoter with other H2A gene promoters.

The human gene for the replication-unlinked histone protein H2A.X is a naturally occurring chimera that contains a replication-unlinked promoter yet produces a stemloop mRNA characteristic of replication-linked histone genes. Consistent with the latter attribute, the H2A.X gene was found to lack introns. The promoter of the H2A.X gene was localized to a 120-base pair region upstream of the transcription start site, a region which included a TATA and two CCAAT sequence elements. The proximal of the two CCAAT elements was shown to be an important determinant of H2A.X gene promoter activity. In a comparative study with the CCAAT elements from the replication-linked H2A.1a gene and the replication-unlinked H2A.Z gene, the proximal CCAAT element of the H2A.X gene was found to bind nuclear factors also bound by CCAAT elements in the latter but not in the former. The specificity of the replication-unlinked H2A.X and H2A.Z gene promoters for CCAAT-binding transcription factors appeared to also reside in short homologous sequences about 10 base pairs away on either side of the CCAAT sequence.

Histone H2A.X gene transcription is regulated differently than transcription of other replication-linked histone genes.

Histone H2A.X is a replication-independent histone H2A isoprotein species that is encoded by a transcript alternatively processed at the 3' end to yield two mRNAs: a 0.6-kb mRNA ending with the stem-loop structure characteristic of the mRNAs for replication-linked histone species, and a second, polyadenylated 1.6-kb mRNA ending about 1 kb further downstream (C. Mannironi, W. M. Bonner, and C. L. Hatch, Nucleic Acids Res. 17:9113-9126, 1989). Of the two, the 0.6-kb H2A.X stem-loop mRNA predominates in many cell lines, indicating that the presence of two types of mRNA may not completely account for the replication independence of H2A.X protein synthesis. The ambiguity is resolved by the finding that the level of the 0.6-kb H2A.X mRNA is only weakly downregulated during the inhibition of DNA replication and only weakly upregulated during the inhibition of protein synthesis, while the levels of other replication-linked mRNAs are strongly down- or upregulated under these two conditions. Analysis of the nuclear transcription rates of specific H2A genes showed that while the rates of transcription of replication-linked H2A genes decreased substantially during the inhibition of DNA synthesis and increased substantially during the inhibition of protein synthesis, the rate of H2A.X gene transcription decreased slightly under both conditions. These differences in transcriptional regulation between the H2A.X gene and other replication-linked histone genes are sufficient to account for the differences in regulation of their respective stem-loop mRNAs.

Risk indicators for periodontitis in a military treatment population.

The association between the periodontal diagnosis and a variety of subject characteristics was studied in a group of 1,783 patients examined at a large military dental clinic. In order of importance, age greater than 30, smoking, male sex, and Filipino racial background were all found to be statistically significant risk indicators for the presence of moderate or advanced periodontitis. A logistic regression equation serving as a predictive model employing these four variables was presented. The strong association found between smoking and advanced periodontitis is consistent with the hypothesis that smoking has cumulative detrimental effects on periodontal health. While these and other risk indicators are neither causative, diagnostic, nor prognostic, they may be helpful in alerting the clinician to more carefully evaluate other clinical signs or laboratory findings of disease.

The prevalence of periodontitis in a military treatment population.

A group of 1,984 males and females (age range 13 to 84) at a military dental clinic were given oral examinations with full-mouth circumferential periodontal probing. Diagnoses were made both for individual quadrants and for the entire mouth using clearly defined diagnostic criteria. The results showed 37% of the subjects had gingivitis only, 33% had early periodontitis, 14% had moderate periodontitis, 15% had advanced periodontitis, 0.5% had juvenile periodontitis, and 0.5% had necrotizing gingivitis. The prevalence of periodontitis increased with age to a peak in the 45- to 50-year-age group. The proportion of periodontitis-affected quadrants, although initially lagging behind the overall case diagnoses, also increased with age.

The human histone H2A.Z gene. Sequence and regulation.

The gene encoding the human basal histone variant H2A.Z has been cloned and sequenced. There is a single functional H2A.Z gene with several pseudogene copies. No other histone genes were found in the 3 kilobases of upstream sequence or in the 0.7 kilobase of downstream sequence. In the upstream region, there are regions of Alu sequences, located about 1375 and 2650 base pairs before the transcription start site. The amount of the H2A.Z transcript is unlinked to DNA replication; however, the amount of the H2A.Z transcript is greatly decreased as proliferating cell cultures become quiescent due in part to a decrease in the rate of transcription. Promoter sequences upstream from the H2A.Z gene have been delineated in IMR-90 cells by chloramphenicol acetyltransferase gene expression. Maximal promoter activity was found in a chloramphenicol acetyltransferase construct that contained 234 base pairs just upstream from the transcription start site. This region includes two GC boxes and three CCAAT boxes as well as a properly positioned TATA box. The organization of the human gene is similar to that of the recently characterized chicken gene (Dalton, S., Robins, A. J., Harvey, R. P., and Wells, J. R. E. (1989) Nucleic Acids Res. 17, 1745-1756). Both have four introns with identical exon-intron borders, but three of the introns in the chicken gene are much longer than those in the human. The promoter regions of the two genes have little overall homology; however, two GC boxes and one of the CCAAT boxes are conserved.

H2A.X. a histone isoprotein with a conserved C-terminal sequence, is encoded by a novel mRNA with both DNA replication type and polyA 3' processing signals.

A full length cDNA clone that directs the in vitro synthesis of human histone H2A isoprotein H2A.X has been isolated and sequenced. H2A.X contains 142 amino acid residues, 13 more than human H2A.1. The sequence of the first 120 residues of H2A.X is almost identical to that of human H2A.1. The sequence of the carboxy-terminal 22 residues of H2A.X is unrelated to any known sequence in vertebrate histone H2A; however, it contains a sequence homologous with those of several lower eukaryotes. This homology centers on the carboxy-terminal tetrapeptide which in H2A.X is SerGlnGluTyr. Homologous sequences are found in H2As of three types of yeasts, in Tetrahymena and Drosophila. Seven of the nine carboxy-terminal amino acids of H2A.X are identical with those of S. cerevisiae H2A.1. It is suggested that this H2A carboxy-terminal motif may be present in all eukaryotes. The H2A.X cDNA is 1585 bases long followed by a polyA tail. There are 73 nucleotides in the 5' UTR, 432 in the coding region, and 1080 in the 3' UTR. Even though H2A.X is considered a basal histone, being synthesized in G1 as well as in S-phase, and its mRNA contains polyA addition motifs and a polyA tail, its mRNA also contains the conserved stem-loop and U7 binding sequences involved in the processing and stability of replication type histone mRNAs. Two forms of H2A.X mRNA, consistent with the two sets of processing signals were found in proliferating cell cultures. One, about 1600 bases long, contains polyA; the other, about 575 bases long, lacks polyA. The short form behaves as a replication type histone mRNA, decreasing in amount when cell cultures are incubated with inhibitors of DNA synthesis, while the longer behaves as a basal type histone mRNA.

Glossodynia as an oral manifestation of diabetes mellitus.

The oral signs and symptoms of glossodynia and xerostomia present a diagnostic problem for the clinician. One of the etiologic considerations in the differential diagnosis should be diabetes mellitus. When diabetes mellitus is suspected, appropriate blood tests should be ordered. If diabetes mellitus is the cause, proper control of the disease will minimize these and other complications and improve the patient's quality of life.

Sequence of cDNAs for mammalian H2A.Z, an evolutionarily diverged but highly conserved basal histone H2A isoprotein species.

The nucleotide sequences of cDNAs for the evolutionarily diverged but highly conserved basal H2A isoprotein, H2A.Z, have been determined for the rat, cow, and human. As a basal histone, H2A.Z is synthesized throughout the cell cycle at a constant rate, unlinked to DNA replication, and at a much lower rate in quiescent cells. Each of the cDNA isolates encodes the entire H2A.Z polypeptide. The human isolate is about 1.0 kilobases long. It contains a coding region of 387 nucleotides flanked by 106 nucleotides of 5'UTR and 376 nucleotides of 3'UTR, which contains a polyadenylation signal followed by a poly A tail. The bovine and rat cDNAs have 97 and 94% nucleotide positional identity to the human cDNA in the coding region and 98% in the proximal 376 nucleotides of the 3'UTR which includes the polyadenylation signal. A potential stem-forming sequence imbedded in a direct repeat is found centered at 261 nucleotides into the 3'UTR. Each of the cDNA clones could be transcribed and translated in vitro to yield H2A.Z protein. The mammalian H2A.Z cDNA coding sequences are approximately 80% similar to those in chicken and 75% to those in sea urchin.

Direct analysis of RNA in whole cell and cytoplasmic extracts by gel electrophoresis.

Procedures are presented by which whole cell, cytoplasmic, or nuclear extracts can be subjected to gel electrophoresis for the separation of the various RNA species, which are then analyzed by conventional blotting and hybridization techniques. Since the methods for preparing the extracts do not involve precipitation or two-phase extraction steps, the minimum number of cells that can be processed is limited only by the sensitivity of detection for specific RNA species. Multiple small or large aliquots of tissue culture cells can be quickly prepared. Cell preparations with high RNase levels, such as resting human lymphocytes or HL60, can be processed reliably with these procedures.

Multiple, shallow, circinate mucosal erosions on the soft palate and base of uvula.

Stomatitis areata migrans is an uncommon oral disease that may affect mucous membranes other than the tongue or be concomitant with geographic tongue. The clinical appearance emulates geographic tongue at an ectopic site, and the lesions rarely are symptomatic.

Histones and their modifications.

Histones constitute the protein core around which DNA is coiled to form the basic structural unit of the chromosome known as the nucleosome. Because of the large amount of new histone needed during chromosome replication, the synthesis of histone and DNA is regulated in a complex manner. During RNA transcription and DNA replication, the basic nucleosomal structure as well as interactions between nucleosomes must be greatly altered to allow access to the appropriate enzymes and factors. The presence of extensive and varied post-translational modifications to the otherwise highly conserved histone primary sequences provides obvious opportunities for such structural alterations, but despite concentrated and sustained effort, causal connections between histone modifications and nucleosomal functions are not yet elucidated.

Identification of ubiquitinated histones 2A and 2B in Physarum polycephalum. Disappearance of these proteins at metaphase and reappearance at anaphase.

Ubiquitinated histones uH2A.1, uH2A.Z, and uH2B have been identified in the basic nuclear proteins of the slime mold Physarum polycephalum by three methods: peptide mapping, cross-reaction with anti-ubiquitin antibody, and uH2A and uH2B isopeptidase cleavage. In microplasmodia, uH2A amounts to 7% of H2A and uH2B amounts to 6% of H2B. Detailed studies of mitosis in Physarum polycephalum macroplasmodia show that in early prophase, which last 15 min, the uH2As and uH2B are both strongly present, whereas minutes later in metaphase, which lasts 7 min, they disappear. When the nuclei enter anaphase, which lasts 3 min, both the uH2As and uH2B reappear. These precise studies suggest that cleavage of ubiquitin from the uH2As and uH2B is a very late, possibly final event in chromosome condensation to metaphase chromosomes and that ubiquitination is an early event in their decondensation. It is proposed that the uH2A and uH2B mark specific regions of the genome which have to be deubiquitinated prior to packaging into metaphase chromosomes; after metaphase these regions are the first to be decondensed and ubiquitinated. This modification, however, is not thought to be a general factor in chromosome condensation but labels a specific subcomponent of chromatin containing the expressed genes of a particular cell type or an important subset of these genes required by the cell to be available for activation, e.g. stress genes.

Plasma catecholamine and hemodynamic responses to the placement of epinephrine-impregnated gingival retraction cord.

A double-blind randomized crossover study was conducted to measure the changes in heart rate, mean arterial blood pressure, pulse pressure product, and plasma catecholamine levels for 60 minutes after the placement of racemic (r) epinephrine- or alum-impregnated retraction cords in intact gingival sulci of nine healthy volunteers. The r-epinephrine-impregnated cord produced significant (p less than 0.01) increases in plasma epinephrine concentrations after 60 minutes, but there were no epinephrine-induced hemodynamic changes. According to these findings, r-epinephrine-impregnated gingival retraction cord placed in an intact, nonlacerated gingival sulcus in a healthy young adult should produce no significant hemodynamic response. It is not known how the placement of epinephrine-impregnated retraction cord would affect elderly or medically compromised patients or patients with lacerated or periodontally involved gingivae.

Minor histone 2A variants and ubiquinated forms in the native H2A:H2B dimer.

Histone octamers from calf thymus were separated into (H3:H4)2 tetramers and H2A:H2B dimers by chromatography through Sephadex G100. The tetramers and dimers were analyzed for variants, ubiquitin adducts, and proteolyzed forms. The minor histone variants H2A.X and H2A.Z were found to be associated with histone H2B as H2A.X:H2B and H2A.Z:H2B dimers, respectively. Ubiquitin adducts of the H2A's and H2B were also present in H2A:H2B dimers.