FlbT, the post-transcriptional regulator of flagellin synthesis in Caulobacter crescentus, interacts with the 5' untranslated region of flagellin mRNA.

Flagellar gene expression' in Caulobacter crescentus is regulated by a complex trans-acting hierarchy, in which the assembly of early structural proteins is required for the expression of later structural proteins. The flagellins that comprise the filament are regulated at both the transcriptional and the post-transcriptional levels. Post-transcriptional regulation is sensitive to the assembly of the flagellar basal body and hook structures. In mutant strains lacking these structures, flagellin genes are transcribed, but not translated. Mutations in the flagellar regulatory gene, flbT, restore flagellin translation in the absence of flagellar assembly. In this report, we investigate the mechanism of FlbT-mediated post-transcriptional regulation. We show that FlbT is associated with the 5' untranslated region (UTR) of fljK (25 kDa flagellin) mRNA and that this association requires a predicted loop structure in the transcript. Mutations within this loop abolished FlbT association and resulted in increased mRNA stability, indicating that FlbT promotes the degradation of flagellin mRNA by associating with the 5' UTR. We also assayed the effects on gene expression using mutant transcripts fused to lacZ. Interestingly, the mutant transcript that failed to associate with FlbT in vitro was still repressed in mutants defective in flagellum assembly, suggesting that other factors in addition to FlbT couple assembly to translation.

The widely conserved Era G-protein contains an RNA-binding domain required for Era function in vivo.

Era is a small G-protein widely conserved in eubacteria and eukaryotes. Although essential for bacterial growth and implicated in diverse cellular processes, its actual function remains unclear. Several lines of evidence suggest that Era may be involved in some aspect of RNA biology. The GTPase domain contains features in common with all G-proteins and is required for Era function in vivo. The C-terminal domain (EraCTD) bears scant similarity to proteins outside the Era subfamily. On the basis of sequence comparisons, we argue that the EraCTD is similar to, but distinct from, the KH RNA-binding domain. Although both contain the consensus VIGxxGxxI RNA-binding motif, the protein folds are probably different. We show that bacterial Era binds RNA in vitro and can form higher-order RNA-protein complexes. Mutations in the VIGxxGxxI motif and other conserved residues of the Escherichia coli EraCTD decrease RNA binding in vitro and have corresponding effects on Era function in vivo, including previously described effects on cell division and chromosome partitioning. Importantly, mutations in L-66, located in the predicted switch II region of the E. coli Era GTPase domain, also perturb binding, leading us to propose that the GTPase domain regulates RNA binding in response to unknown cellular cues. The possible biological significance of Era RNA binding is discussed.

The relationships between premilitary school record data and risk for posttraumatic stress disorder among Vietnam war veterans.

The purpose of this study was to determine whether Vietnam veterans' risk for posttraumatic stress disorder (PTSD) was correlated with their premilitary school performance. The authors compared both primary and secondary school record data on hospitalized chemically dependent PTSD patients with those of both non-PTSD, chemically dependent and community controls. All participants were male Vietnam war combat veterans. The comparisons were made with MANCOVA analyses with the effects of combat and age differences between groups controlled. For the most part, primary-school grade point average, absenteeism, and tardiness data on three groups did not differ significantly. However, the mean secondary school grade points of the future PTSD patients were generally substantially lower than those of controls. Additionally, more secondary school absenteeism and tardiness were reported among future PTSD patients than in the controls. The groups did not differ significantly on number of extracurricular activities. Academic weakness, absenteeism, and tardiness in secondary school appear to be moderately strong predictors of vulnerability to PTSD after traumatization. It also supports the claim that chronic PTSD is, in part, the result of weaknesses present before exposure to trauma.

Molecular support for field cancerization in the head and neck.

BACKGROUND: Two competing concepts, field cancerization and micrometastatic lesions, have been postulated to account for the high frequency of second primary tumors and multicentric dysplasia in patients with head and neck carcinoma. METHODS: To provide insight into this process, the authors examined histologically normal mucosa and dysplastic tissue adjacent to invasive tumor for loss of heterozygosity (LOH) at three commonly deleted loci. Tissues from 21 patients with carcinoma of the oral cavity and oropharynx were identified and verified by a pathologist to contain histologically normal mucosa, dysplasia, and adjacent invasive squamous cell carcinoma. Each specimen was analyzed for LOH at D9S171 (9p21), D3S1007 (3p21.3-22), and D3S1228 (3p14). RESULTS: Of the 21 patients, 19 had adequate DNA for analysis. Seventeen patients were heterozygous at one or both of the 3p sites and LOH occurred in 6 of 17 invasive tumor specimens, 1 of 17 dysplasia specimens, and in none of the mucosal specimens. LOH at 9p21 occurred in 11 of 13 informative specimens of invasive tumor, 8 of 13 dysplasia specimens, and 6 of 13 normal mucosa specimens. However, one case that did not have 9p deletion in the tumor demonstrated LOH in the mucosa and two cases had LOH in both the tumor and mucosa but with deletion of the opposite allele. CONCLUSIONS: These data suggest that 9p21 but not 3p14 or 3p21 deletions occur in the absence of histologic changes. In two cases preinvasive and invasive lesions that apparently were an example of histologic progression contained disparate genetic events, calling into question the use of adjacent dysplasia as a model for premalignant lesions.

Relative accuracy of fine-needle aspiration and frozen section in the diagnosis of well-differentiated thyroid cancer.

The need for and extent of thyroid surgery for a thyroid nodule is usually primarily based on fine-needle aspiration (FNA) and frozen section diagnosis. The relative role of these modalities in 66 patients who had undergone FNA and subsequent thyroidectomy with frozen section was investigated. Cases that demonstrated discordance between FNA and frozen section (n = 22; 33%) were identified, and all slides were re-reviewed by a cytopathologist using current established cytologic criteria. A change in diagnosis was made in 13 cases with an increase in accuracy of FNA from 71% to 88%. The accuracy of frozen section (92%) did not change appreciably with re-review (94%). The accuracy of FNA and frozen section combined was found to be 98%. The rate of discordance decreased from 33% to 13% with re-review. When strict histologic and cytologic criteria are applied, FNA and frozen section are accurate and complementary methods that help in determining the operative management of thyroid masses. However, when FNA yields a diagnosis of "follicular neoplasm," frozen section is unlikely to change this diagnosis.

Social maladjustment indicators in PTSD patients' families of origin.

We compared the frequencies with which PTSD patients, psychiatric controls, and hospital employee controls reported that their fathers, mothers, and oldest siblings of each sex had been incarcerated or had received psychiatric/psychological treatment. We also compared estimates of the number of psychiatric hospitalizations, incarcerations, courses of outpatient treatment, treatment sessions, and days of institutionalization undergone by the relatives. Only a chance number of significant differences appeared, which suggests that general psychosocial maladjustment in one's family of origin does not appear to increase trauma survivors' risk for PTSD.

Structure and regulation of the Salmonella typhimurium rnc-era-recO operon.

The Escherichia coli rnc-era-recO operon encodes ribonuclease III (RNase III; a dsRNA endonuclease involved in rRNA and mRNA processing and decay), Era (an essential G-protein of unknown functions and RecO (involved in the RecF homologous recombination pathway). Expression of the rnc and era genes is negatively autoregulated: RNase III cleaves the rncO 'operator' in the untranslated leader, destabilizing the operon mRNA. As part of a larger effort to understand RNase III and Era structure and function, we characterized rnc operon structure, function and regulation in the closely related bacterium Salmonella typhimurium. Construction of a S typhimurium strain conditionally defective for RNase III and Era expression showed that Era is essential for cell growth. This mutant strain also enabled selection of recombinant clones containing the intact S typhimurium rnc-era-recO operon, whose nucleotide sequence, predicted protein sequence, and predicted rncO RNA secondary structure were all highly conserved with those of E coli. Furthermore, genetic and biochemical analysis revealed that S typhimurium rnc gene expression is negatively autoregulated by a mechanism very similar or identical to that in E coli, and that the cleavage specificities of RNase IIIs.t. and RNase IIIE.c. are indistinguishable with regard to rncO cleavage and S typhimurium 23S rRNA fragmentation in vivo.

Prolonged treatment with omeprazole does not improve the eradication rate of Helicobacter pylori infection--a short report [corrected].

Omeprazole has been shown to have a suppressive effect on Helicobacter pylori. The aim of this study was to determine if prolonged treatment with omeprazole would result in a higher eradication rate than short course treatment. Twenty patients with endoscopy proven duodenal ulcers and unequivocal evidence of Helicobacter pylori (HP) infection based on culture, histology, urease test and Gram's stain of a fresh tissue smear were treated with omeprazole 40 mg om for 2-4 weeks. Following ulcer healing, patients received either maintenance omeprazole 20 mg om or placebo for up to one year. All 20 patients had healed ulcers following a 2-4 week course of omeprazole 40 mg om.. All were negative for HP at the end of treatment. Thirteen patients received short course therapy with omeprazole only, followed by placebo. On follow-up endoscopy at 3 months, only one of 13 (7.7%) had eradicated the bacteria. Seven patients received maintenance treatment with omeprazole 20mg om for one year. Following completion of treatment, patients were followed up at 1, 3 and 6 months. Only one of 7 (14.3%) patients had eradicated the infection on long term follow-up. The eradication rates of HP with both short and long course omeprazole monotherapy were low.

Posttraumatic stress disorder (PTSD) symptoms in PTSD patients' families of origin.

Posttraumatic stress disorder (PTSD) patients, psychiatric controls, and hospital employee controls rated their father, mother, and oldest sibling of each sex on 14 PTSD Interview (PTSD-I) symptom ratings. The stress disorder patients assigned their relatives significantly higher PTSD-I ratings than the control group members did in 35 of 120 comparisons. The number of significant differences was nearly identical in the fathers, mothers, sisters, and brothers. Differences were particularly frequent on items pertaining to intrusive thoughts, impoverished relationships, and guilt. The results suggest that a trauma survivor's risk for PTSD may be related to his family's history for PTSD-like behaviors.