Oncology team perspectives on distress screening: a multisite study of a well-established use of patient-reported outcomes for clinical assessment.

PURPOSE: Cancer care team attitudes towards distress screening are key to its success and sustainability. Previous qualitative research has interviewed staff mostly around the startup phase. We evaluate oncology teams' perspectives on psychosocial distress screening, including perceived strengths and challenges, in settings where it has been operational for years. METHODS: We conducted, transcribed, and analyzed semi-structured interviews with 71 cancer care team members (e.g., MDs, RNs, MSWs) at 18 Commission on Cancer-accredited cancer programs including those serving underrepresented populations. RESULTS: Strengths of distress screening identified by participants included identifying patient needs and testing provider assumptions. Staff indicated it improved patient-provider communication and other aspects of care. Challenges to distress screening included patient barriers (e.g., respondent burden) and lack of electronic system interoperability. Participants expressed the strengths of distress screening (n = 291) more than challenges (n = 86). Suggested improvements included use of technology to collect data, report results, and make referrals; complete screenings prior to appointments; longitudinal assessment; additional staff training; and improve resources to address patient needs. CONCLUSION: Cancer care team members' perspectives on well-established distress screening programs largely replicate findings of previous studies focusing on the startup phase, but there are important differences: team members expressed more strengths than challenges, suggesting a positive attitude. While our sample described many challenges described previously, they did not indicate challenges with scoring and interpreting the distress screening questionnaire. The differences in attitudes expressed in response to mature versus startup implementations provide important insights to inform efforts to sustain and optimize distress screening.

Shame and Depressive Symptoms: Self-compassion and Contingent Self-worth as Mediators?

Research has identified the experience of shame as a relevant predictor of depressive symptoms. Building upon resilience theory, this is the first study to investigate if self-compassion and/or contingent self-worth (i.e., family support and God's love) mediate the link between shame and depressive symptoms. Participants were 109 African Americans, within the age range of 18 and 64, who sought service following a suicide attempt from a public hospital that serves mostly low-income patients. Findings suggest that shame was related to depressive symptoms through self-compassion but not through contingent self-worth, underscoring the significant role that self-compassion plays in ameliorating the aggravating effect of shame on depressive symptoms. Results highlight the value of incorporating self-compassion training into interventions for suicidal African Americans in an effort to reduce the impact of shame on their depressive symptoms and ultimately their suicidal behavior and as a result enhance their capacity for resilience.

Anterior ST-elevation myocardial infarction induced by rituximab infusion: A case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVES: Rituximab is a chimeric monoclonal anti-CD20 antibody approved for the treatment of some lymphoid malignancies as well as for autoimmune diseases including rheumatoid arthritis (RA), idiopathic thrombocytopenic purpura (ITP) and vasculitis. Generally, rituximab is well tolerated; nevertheless, some patients develop adverse effects including infusion reactions. Albeit rare, these reactions may in some cases be life-threatening conditions. Rituximab cardiovascular side effects include more common effects such as hypertension, oedema and rare cases of arrhythmias and myocardial infarction. CASE SUMMARY: In this article, we report a case of a 58-year-old man with a history of overlap syndrome including RA and limited scleroderma who was treated with rituximab and developed a dramatic ST-elevation myocardial infarction (STEMI) during the drug administration. WHAT IS NEW AND CONCLUSION: This report underlines previous published reports emphasizing the awareness of such an association. This communication also warrants the importance of screening for ischaemic heart disease in selected cases of patients treated with rituximab.

Effects of a culturally informed intervention on abused, suicidal African American women.

This study examined (a) the relative efficacy of a culturally sensitive empowerment group intervention (Nia) aimed at increasing 3 protective factors-self-esteem, hopefulness, and effectiveness of obtaining resources-versus treatment as usual (TAU) for low-income, abused African American women who recently had attempted suicide and (b) the impact of participants' readiness to change with regard to their abusive relationship and suicidal behavior on their levels of each protective factor in the 2 conditions. The sample included 89 African American women who reported intimate partner violence (IPV) exposure and a recent suicide attempt. Multivariate general linear modeling revealed that those in Nia showed greater improvements in self-esteem, but not in hopefulness or effectiveness of obtaining resources. However, significant interactions emerged in which participants who were "less ready to change" (i.e., earlier in the stages of change process) their IPV situation and suicidal behavior endorsed greater levels of hopefulness and perceived effectiveness of obtaining resources, respectively, following Nia. Findings suggest that abused, suicidal African American women who are more reluctant initially to changing their abusive situation and suicidal behavior may benefit from even a brief, culturally informed intervention.

Identification of the gene causing mucolipidosis type IV.

Mucolipidosis type IV (MLIV) is an autosomal recessive, neurodegenerative, lysosomal storage disorder characterized by psychomotor retardation and ophthalmological abnormalities including corneal opacities, retinal degeneration and strabismus. Most patients reach a maximal developmental level of 12?15 months. The disease was classified as a mucolipidosis following observations by electron microscopy indicating the lysosomal storage of lipids together with water-soluble, granulated substances. Over 80% of the MLIV patients diagnosed are Ashkenazi Jews, including severely affected and mildly affected patients. The gene causing MLIV was previously mapped to human chromosome 19p13.2-13.3 in a region of approximately 1 cM (ref. 7). Haplotype analysis in the MLIV gene region of over 70 MLIV Ashkenazi chromosomes indicated the existence of two founder chromosomes among 95% of the Ashkenazi MLIV families: a major haplotype in 72% and a minor haplotype in 23% of the MLIV chromosomes (ref. 7, and G.B., unpublished data). The remaining 5% are distinct haplotypes found only in single patients. The basic metabolic defect causing the lysosomal storage in MLIV has not yet been identified. Thus, positional cloning was an alternative to identify the MLIV gene. We report here the identification of a new gene in this human chromosomal region in which MLIV-specific mutations were identified.

The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy.

Hereditary inclusion body myopathy (HIBM; OMIM 600737) is a unique group of neuromuscular disorders characterized by adult onset, slowly progressive distal and proximal weakness and a typical muscle pathology including rimmed vacuoles and filamentous inclusions. The autosomal recessive form described in Jews of Persian descent is the HIBM prototype. This myopathy affects mainly leg muscles, but with an unusual distribution that spares the quadriceps. This particular pattern of weakness distribution, termed quadriceps-sparing myopathy (QSM), was later found in Jews originating from other Middle Eastern countries as well as in non-Jews. We previously localized the gene causing HIBM in Middle Eastern Jews on chromosome 9p12-13 (ref. 5) within a genomic interval of about 700 kb (ref. 6). Haplotype analysis around the HIBM gene region of 104 affected people from 47 Middle Eastern families indicates one unique ancestral founder chromosome in this community. By contrast, single non-Jewish families from India, Georgia (USA) and the Bahamas, with QSM and linkage to the same 9p12-13 region, show three distinct haplotypes. After excluding other potential candidate genes, we eventually identified mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene in the HIBM families: all patients from Middle Eastern descent shared a single homozygous missense mutation, whereas distinct compound heterozygotes were identified in affected individuals of families of other ethnic origins. Our findings indicate that GNE is the gene responsible for recessive HIBM.

Nitrogen-sparging assisted anoxic biological drinking water treatment system.

Existing heterotrophic denitrification reactors rely on microorganisms to consume dissolved oxygen (DO) and create conditions suitable for denitrification, but this practice leads to excessive microbial growth and increased organic carbon doses. An innovative reactor that uses nitrogen gas sparging through a contactor to strip DO was developed and tested in the lab. It reduced influent nitrate from 15 to <1 mg/L as N with nitrite accumulation <1 mg/L as N. It maintained a consistent flow rate and developed minimal headloss, making it easier to operate than the denitrifying dual-media filter that was operated in parallel. Gravel, polyvinyl chloride pieces, and no packing media were assessed as options for the nitrogen-sparged contactor, and gravel was found to support denitrification at the highest loading rate and was resilient to nitrogen-sparging shutoffs and intermittent operation. This innovative reactor appears promising for small drinking water systems.

Depth profiles of biological aerated contactors: Characterizing microbial activity treating reduced contaminants.

The biological treatment process consisting of an aerated contactor and filter is effective for groundwaters containing elevated ammonia and other reduced contaminants, including iron, manganese, arsenic, and methane. Depth profiles characterizing microbial activity across aerated contactors are lacking. A 1-year pilot study comparing gravel- and ceramic-packed contactors was conducted, and media depth profile samples were collected at the conclusion of the study. Media and water samples also were collected from pilot-scale aerated contactors at 4 other water systems. Water quality, media surface metals concentrations, and a suite of biofilm parameters were analyzed. Media surface metals concentrations were greatest at the influent end. ATP concentrations, extracellular polymeric substances, and extracellular enzyme activities tended to be similar across depth. Bacteria and functional genes involved in contaminant oxidation co-occurred and tended to decrease across depth, but were not correlated to the media metals concentration. Microbial community composition changed with depth, and the diversity either decreased or remained similar. The microbial activity profiles through aerated contactors differed from what is typically reported for groundwater biofilters, suggesting that the different reactor flow and dissolved oxygen profiles impacted the microbial community.

Comprehensive characterization of aerobic groundwater biotreatment media.

Aerobic biotreatment systems can treat multiple reduced inorganic contaminants in groundwater, including ammonia (NH3), arsenic (As), iron (Fe), and manganese (Mn). While individual systems treating multiple contaminants simultaneously have been characterized and several systems treating one contaminant have been compared, a comparison of systems treating co-occurring contaminants is lacking. This study assessed the treatment performance and microbial communities within 7 pilot- and full-scale groundwater biotreatment systems in the United States that treated waters with pH 5.6-7.8, 0.1-2.0 mg/L dissolved oxygen, 75-376 mg CaCO3/L alkalinity, < 0.03-3.79 mg NH3-N/L, < 4-31 µg As/L, < 0.01-9.37 mg Fe/L, 2-1220 µg Mn/L, and 0.1-5.6 mg/L total organic carbon (TOC). Different reactor configurations and media types were represented, allowing for a broad assessment of linkages between water quality and microbial communities via microscopy, biofilm quantification, and molecular methods. Influent NH3, TOC, and pH contributed to differences in the microbial communities. Mn oxidase gene copy numbers were slightly negatively correlated with the influent Mn concentration, but no significant relationships between gene copy number and influent concentration were observed for the other contaminants. Extracellular enzyme activities, community composition, and carbon transformation pathways suggested heterotrophic bacteria may be important in nitrifying biofilters. Aerobic groundwater biofilters are complex, and improved understanding could lead to engineering enhancements.

Single-molecule visualization determines conformational substate ensembles in ß-sheet-rich peptide fibrils.

An understanding of protein conformational ensembles is essential for revealing the underlying mechanisms of interpeptide recognition and association. However, experimentally resolving multiple simultaneously existing conformational substates remains challenging. Here, we report the use of scanning tunneling microscopy (STM) to analyze the conformational substate ensembles of ß sheet peptides with a submolecular resolution (in-plane <2.6 Å). We observed ensembles of more than 10 conformational substates (with free energy fluctuations between several kBTs) in peptide homoassemblies of keratin (KRT) and amyloidal peptides (-5Aß42 and TDP-43 341-357). Furthermore, STM reveals a change in the conformational ensemble of peptide mutants, which is correlated with the macroscopic properties of peptide assemblies. Our results demonstrate that the STM-based single-molecule imaging can capture a thorough picture of the conformational substates with which to build an energetic landscape of interconformational interactions and can rapidly screen conformational ensembles, which can complement conventional characterization techniques.

Fate of ammonia and implications for distribution system water quality at four ion exchange softening plants with elevated source water ammonia.

Hard water and elevated ammonia are problems for many United States groundwater drinking water utilities, and some utilities, particularly those in the Midwest, face both challenges. Ion (cation) exchange (IX) is a common treatment technique for hardness reduction (i.e., softening) and may be used to remove ammonia as well, but these constituents may compete in IX and impact overall treatment performance. Few data have been reported on the impact on ammonia concentrations when using IX for softening in full-scale systems. This study investigated four full-scale groundwater treatment plants in Illinois that practice IX for softening (raw water hardness > 220 mg/L as CaCO3) and have elevated groundwater ammonia concentrations (> 2 mg N/L). Sampling throughout the year revealed consistent finished water hardness levels but variable ammonia concentrations. Ammonia removal varied and depended on how much water had been treated since the last regeneration. High ammonia removal (sometimes > 90%) occurred in the first half of the IX service cycle, while effluent ammonia concentrations increased compared to the influent (sometimes > 200%) towards the end of the IX cycle (total length 50,000-92,000 gallons [190-350 m3]). Ammonia removal efficiency varied among the plants, but the overall trends were similar. Because variable ammonia concentrations may make it difficult to produce a consistent total chlorine residual, they can negatively impact disinfection and water quality in the distribution system. Ammonia concentrations should be considered when designing softening systems to determine regeneration frequency, develop blending strategies, or include an alternative ammonia treatment process before IX softening to produce a more stable and consistent finished water.

Gastrointestinal and hepatic manifestations of COVID-19: A systematic review and meta-analysis.

Background and Aim: This review investigates the role of gastrointestinal and hepatic manifestations in COVID-19, particularly with regard to the prevalence of isolated gastrointestinal (GI) symptoms. Methods: We searched PubMed, Embase, and Cochrane library for COVID-19 publications from 1 December 2019 to 18 May 2020. We included any study that reported the presence of GI symptoms in a sample of >5 COVID-19 patients. Data collection and risk of bias assessment were performed independently by two reviewers. Where ≥3 studies reported data sufficiently similar to allow calculation of a pooled prevalence, we performed random effects meta-analysis. Results: This review included 17 776 COVID-19 patients from 108 studies. Isolated GI symptoms only occurred in 1% (95% confidence interval [CI] 0-6%) of patients. GI symptoms were reported in 20% (95% CI 15-24%) of patients. The most common were anorexia (21%, 95% CI 15-27%), diarrhea (13%, 95% CI 11-16%), nausea or vomiting (8%, 95% CI 6-11%), and abdominal pain (4%, 95% CI 2-6%). Transaminase elevations were present in 24% (95% CI 17-31%) of patients. Higher prevalence of GI symptoms were reported in studies published after 1st April, with prevalence of diarrhea 16% (95% CI 13-20), nausea or vomiting 12% (95% CI 8-16%), and any GI symptoms 24% (95% CI 18-34%). GI symptoms were associated with severe COVID-19 disease (odds ratio [OR] 2.1, 95% CI 1.3-3.2), but not mortality (OR 0.90, 95% CI 0.52-1.54). Conclusions: Patients with isolated GI symptoms may represent a small but significant portion of COVID-19 cases. When testing resources are abundant, clinicians should still consider testing patients with isolated GI symptoms or unexplained transaminase elevations for COVID-19. More recent studies estimate higher overall GI involvement in COVID-19 than was previously recognized.

Further evidence for association of the RGS2 gene with antipsychotic-induced parkinsonism: protective role of a functional polymorphism in the 3'-untranslated region.

RGS2 (regulator of G-protein signaling 2) modulates dopamine receptor signal transduction. Functional variants in the gene may influence susceptibility to extrapyramidal symptoms (EPS) induced by antipsychotic drugs. To further investigate our previous report of association of the RGS2 gene with susceptibility to antipsychotic-induced EPS, we performed a replication study. EPS were rated in 184 US patients with schizophrenia (115 African Americans, 69 Caucasian) treated for at least a month with typical antipsychotic drugs (n=45), risperidone (n=46), olanzapine (n=50) or clozapine (n=43). Six single nucleotide polymorphisms (SNPs) within or flanking RGS2 were genotyped (rs1933695, rs2179652, rs2746073, rs4606, rs1819741 and rs1152746). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. Our results indicate association of SNP rs4606 with antipsychotic-induced parkinsonism (AIP), as measured by the Simpson Angus scale, in the overall sample and in the African-American subsample, the G (minor) allele having a protective effect. ORs for AIP among rs4606 G-allele carriers were 0.23 (95% CI 0.10-0.54, P=0.001) in the overall sample, and 0.20 (0.07-0.57, P=0.003) in the African-American subsample. In the previously studied Israeli sample the OR was 0.31 (0.11-0.84, P=0.02). We completely sequenced the RGS2 gene in nine patients with AIP and nine patients without, from the Israeli sample. No common coding polymorphisms or additional regulatory variants were revealed, suggesting that association of the rs4606 C/G polymorphism with AIP is biologically meaningful and not a consequence of linkage disequilibrium with another functional variant. Taken together, the findings of the current study support the association of RGS2 with AIP and focus on a possible protective effect of the minor G allele of SNP rs4606. This SNP is located in the 3'-regulatory region of the gene, and is known to influence RGS2 mRNA levels and protein expression.

Evidence for an interaction of schizophrenia susceptibility loci on chromosome 6q23.3 and 10q24.33-q26.13 in Arab Israeli families.

A genome scan for schizophrenia related loci in Arab Israeli families by Lerer et al. [Lerer et al. (2003); Mol Psychiatry 8:488-498] detected significant evidence for linkage at chromosome 6q23. Subsequent fine mapping [Levi et al. (2005); Eur J Hum Genet 13:763-771], association [Amann-Zalcenstein et al. (2006); Eur J Hum Genet 14:1111-1119] and replication studies [Ingason et al. (2007); Eur J Hum Genet 15:988-991] identified AHI1 as a putative susceptibility gene. The same genome scan revealed suggestive evidence for a schizophrenia susceptibility locus in the 10q23-26 region. Genes at these two loci may act independently in the pathogenesis of the disease in our homogeneous sample of Arab Israeli families or may interact with each other and with other factors in a common biological pathway. The purpose of our current study was to test the hypothesis of genetic interaction between these two loci and to identify the type of interaction between them. The initial stage of our study focused on the 10q23-q26 region which has not been explored further in our sample. The second stage of the study included a test for possible genetic interaction between the 6q23.3 locus and the refined 10q24.33-q26.13 locus. A final candidate region of 19.9 Mb between markers D10S222 (105.3 Mb) and D10S587 (125.2 Mb) was found on chromosome 10 by non-parametric and parametric linkage analyses. These linkage findings are consistent with previous reports in the same chromosomal region. Two-locus multipoint linkage analysis under three complex disease inheritance models (heterogeneity, multiplicative, and additive models) yielded a best maximum LOD score of 7.45 under the multiplicative model suggesting overlapping function of the 6q23.3 and 10q24.33-q26.13 loci.

Mothers' reflections about infant irritability and postpartum tobacco use.

BACKGROUND: Recent research has shown that most women who stop or substantially reduce cigarette smoking during pregnancy return to previous levels of tobacco use soon after delivery. The determinants of postpartum tobacco use have not been adequately identified. To address this gap, the present study examined one potential contributor to postpartum smoking, namely, unexplained infant crying and fussiness. The purpose of this study was to describe mothers' reflections about perceived infant irritability and postpartum tobacco use. METHODS: A qualitative descriptive approach was applied to the responses of low-income women who participated in a mixed methods study of smoking relapse among mothers of infants. The subset of mothers for the present study (n = 86) was composed of women who intended to be nonsmokers after delivery. Thematic content analysis was conducted of the texts from their interviews. RESULTS: Four major themes were identified with respect to perceptions of infant irritability and postpartum tobacco use: not knowing what to do, seeking renewal, seeking relief, and evaluating self. CONCLUSIONS: The reflections of the study participants suggest that the challenges of handling infant irritability often trigger thoughts of smoking or smoking behavior. Health practitioners may strengthen cessation interventions by using strategies to help mothers cope with this experience, which is unique to the first few months after delivery.

Aspirin withdrawal in patients treated with ticagrelor presenting with non-ST elevation myocardial infarction.

Essentials Strong P2Y12 blockade may cause platelet inhibition that is only minimally enhanced by aspirin. We evaluated aspirin withdrawal on platelet reactivity in ticagrelor treated patients. Aspirin withdrawal resulted in increased platelet reactivity to arachidonic acid. Aspirin withdrawal caused little difference in adenosine diphosphate-induced platelet aggregation. SUMMARY: Background Recent studies have shown that the thromboxane A2 -dependent pathway is dependent on the ADP-P2Y12 pathway, and that strong P2Y12 receptor blockade alone causes inhibition of platelet aggregation that is minimally enhanced by aspirin. Data from the PLATO trial suggested that, among ticagrelor-treated patients, high-dose versus low-dose (< 100 mg day-1 ) aspirin is associated with an increased risk fof ischemic events. Objectives To evaluate the impact of aspirin withdrawal on platelet reactivity in acute coronary syndrome (ACS) patients treated with a potent P2Y12 blocker. Patients/Methods This was a current prospective, randomized, placebo-controlled, double-blind, cross-over study. The study population comprised 22 consecutive ACS patients who underwent percutaneous coronary intervention and were treated with aspirin (100 mg day-1 ) and ticagrelor. Thirty days post-ACS, open-label aspirin was stopped, and patients were randomized to either blinded aspirin or placebo for 2 weeks, with each patient crossing over to the other arm for an additional 2 weeks. Platelet reactivity to arachidonic acid and ADP determined with light-transmission aggregometry (LTA) and VerifyNow was evaluated at baseline, and 2 weeks and 4 weeks later. Results Aspirin withdrawal resulted in an increase in arachidonic-acid induced platelet reactivity as determined with both LTA (77.0% ± 11.3% versus 20.8% ± 4.4%) and VerifyNow (607.7 ± 10.6 aspirin reaction units [ARU] versus 408.5 ± 14.4 ARU). Platelet response to ADP, as determined with both LTA and VerifyNow, did not differ with either aspirin or placebo (32.9% ± 2.6% versus 35.8% ± 3.6%, and 33.5 ± 6.4 P2Y12 reaction units (PRU) versus 29.6 ± 5.7 PRU, respectively). Conclusions Aspirin withdrawal early post-ACS results in increased platelet reactivity in response to arachidonic acid, despite concomitant treatment with the potent P2Y12 blocker ticagrelor.

Strokes after cardiac surgery: mostly right hemispheric ischemic with mild residual damage.

OBJECTIVE: Since cardiac surgery is now performed on patients with high risk for cerebrovascular disease, we studied the clinical findings and medium term outcome of patients with acute stroke/transient ischemic attack (TIA) after cardiac surgery. METHODS: All consecutive patients with acute stroke/TIA after cardiac surgery were prospectively observed during a 19 month period. Follow-up was between 3 months and 21 months. Risk factors, type of stroke, anatomic localization, initial neurological deficit and followup outcome were evaluated, using standard assessment scores. RESULTS: Among 406 patients operated (mean age 64.3 +/- 12.7 years, 284 males), 18 developed stroke and 2 TIAs (mean age 65.7 years, 13 males). There were no cases of intracerebral hemorrhage. Most of the strokes happened shortly after valve surgery (mean 1.3 days post operatively) and were right hemispheric (right = 11, left = 3; p = 0.034). Vertebrobasilar stroke appearance was delayed (mean: 8.25 days post operatively); they were attributed mostly to cardiac arrhythmias. Stroke/TIA patients did not have a higher preoperative risk than those without, but their cardiac functional score was worse (p = 0.01), and the average cardiopulmonary bypass time during surgery was longer (p = 0.009). Two patients died in hospital, both with vertebrobasilar stroke. Most of the hemispheric stroke patients became functionally independent (mean modified Rankin Scale < 2), even those with initial severe deficit. CONCLUSION: Strokes after cardiac surgery are mostly right hemispheric and exclusively ischemic. Outcome is relatively fair. We suggest an embolic injury to the right hemisphere, procedure related, as a possible mechanism.

Self-care operations and nursing interventions for children with cancer and their parents.

As individuals assume more responsibility for their healthcare, nurses need to explore methods to support families' self-care practices. The purpose of this qualitative study was to: (a) determine what self-care and dependent-care operations children and parents perform to address self-care requisites, and (b) explore nursing interventions to promote operations. Orem's theory of self-care, theory of self-care deficit, and theory of nursing system were employed. Twenty-seven participants were interviewed about their cancer experiences. Results were that children and parents performed estimative, transitional, and productive operations to meet self-care requisites. Various nursing interventions that promoted these operations were identified. Recommendations were made for further interventions to support families.

Transcription elongation of the murine ornithine decarboxylase (ODC) gene is regulated in vitro at two downstream elements by different attenuation mechanisms.

Ornithine decarboxylase (ODC) plays an important role in cell proliferation. Its expression is tightly regulated at the mRNA and protein levels and is found to be deregulated in various malignancies. The rapid and dramatic induction of cellular ODC mRNA upon serum addition raised the possibility that a transcriptional attenuation mechanism may be involved in the regulation of ODC gene expression. Using transcription in HeLa nuclear extract and isolated transcription complexes, we have identified two sites of transcription arrest downstream to the transcription start site: Attenuator 1 (Att.1) located at +220, near two repeats of a USF/Myc-Max binding consensus sequence and attenuator 2 (Att.2) located at +1590 near a long stretch of T-residues. The two attenuators exhibit distinct properties as revealed by elongation of briefly initiated and partially purified transcription complexes: Att.1 serves as a transient pause site while arrest at Att.2 is more prolonged. The arrest at both attenuators is modulated by the general elongation factor TFIIS. In a promoter independent transcription system, using partially purified RNA polymerase II, only Att.2 was recognized efficiently. This suggests that the recognition of Att.2 is an intrinsic property of the polymerase while Att.1 recognition has to be facilitated by an auxiliary factor/s.

Reaction of T7 DNA with a polycyclic aromatic hydrocarbon. Lack of structural perturbation.

Bacteriophage T7 DNA reacts uniformly with trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene(anti-BPDE). The reaction product retains the native configuration so that only one site sensitive to S1 nuclease is produced for every 70 anti-BPDE adducts. DNA treated with anti-BPDE is retained on benzoylated naphthoylated DEAE-cellulose even after washing with 1.0 M salt solutions. About 100 adducts per T7 molecule are required for adherence which is not due to breaks or single-stranded regions since adherence is not affected by S1 nuclease treatment. The binding of anti-BPDE reacted DNA to benzoylated naphthoylated DEAE-cellulose is cooperative and requires many residues per bound fragment. Treatment of T7 DNA treated with anti-BPDE with restriction endonuclease yields smaller molecules, still containing adducts, which do not adhere. We interpret these results to mean that reaction with BPDE does not involve deformation of the DNA structure and that the adducts lie in a position which they are readily accessible for interaction with aromatic groups on the column resin.