Pregnancy complications, treatment characteristics and birth outcomes in women with atopic dermatitis in Denmark.

BACKGROUND: The risk of prenatal, obstetric and birth complications in mothers with atopic dermatitis (AD), along with treatment use during pregnancy, is unknown. OBJECTIVES: To examine the associations between prenatal, obstetric and birth complications in mothers with AD and describe the dermatologic care received during pregnancy. METHODS: Mother-child pairs, in which the mother had a history of AD, were identified through the Danish Medical Birth Registry and matched 1 : 10 with non-AD pairs. Data on dermatologic treatment and prenatal, obstetric and birth complications were obtained through linkage via nationwide registers. Multiple logistic regression was performed. RESULTS: We identified 10 668 births from 1997 through 2014 to women with AD. Women with a hospital/ambulatory contact for AD during pregnancy had increased topical corticosteroid and ultraviolet therapy use during pregnancy compared to prior. However, overall, women with AD received decreased dermatologic therapy during pregnancy compared to prior. In adjusted analysis, maternal AD was inversely associated with gestational diabetes [OR 0.79, 95% CI (0.68-0.92)], but positively associated with premature rupture of membranes [1.15 (1.05-1.27)] and staphylococcal neonatal septicemia [2.45 (1.33-4.49)]-albeit the latter was rare. These associations did not meet statistical significance in sub-analysis where body mass index data were available. No associations were found with preeclampsia, prematurity or non-staphylococcal neonatal septicaemia. CONCLUSIONS: Women with AD during pregnancy mainly used topical corticosteroids and ultraviolet therapy to control their disease. While premature rupture of membranes and staphylococcal neonatal septicaemia were over-represented in maternal AD, no associations were found with any other significant prenatal, obstetric or birth outcome.

Association between parental autoimmune disease and atopic dermatitis in their offspring: a matched case-control study.

BACKGROUND: Atopic dermatitis (AD) is associated with many autoimmune diseases, in part due to overlapping genetic risk loci. While parental atopic disease is an important risk for AD in the offspring, little is known on the putative associations between parental autoimmune disease and AD in their children. MATERIALS AND METHODS: All children born between 1996 and 2011 who received a diagnosis of AD in the hospital system before their fifth birthday were matched 1 : 10 with children from the general population. Maternal and paternal autoimmune diseases were assessed using registry-based data. Conditional logistic regression was performed on the relationships between parental autoimmune diseases and AD in their children. RESULTS: A total of 8589 children with AD were matched with controls. One or more autoimmune disease was identified in 5.89% (506/8589) of mothers to AD children and 3.67% (315/8589) of fathers to AD children compared to 4.85% (4163/85 890) and 3.28% (2816/85 890) in parents of control children. Maternal autoimmune disease but not paternal autoimmune disease was associated with AD in the offspring (odds ratio [OR] 1.20 [95% confidence interval (CI) 1.20-1.32] and OR 1.08 [0.96-1.22], respectively), Two or more maternal autoimmune diseases, maternal dermatologic autoimmune disease and maternal digestive autoimmune disease were all also associated with AD development in her children (1.96 [95% CI 1.36-2.84], OR 1.60 [95% CI 1.24-2.07] and OR 1.24 [95% CI 1.06-1.45], respectively). CONCLUSIONS: The risk of AD is influenced by many factors including atopy status and filaggrin gene mutations. In this matched case-control study, maternal autoimmune disease was associated with AD diagnosis in the offspring. Maternal dermatologic and digestive autoimmune diseases were most closely associated with subsequent AD diagnosis in the offspring.

Exploring the association between parental psychiatric disease and childhood atopic dermatitis: a matched case-control study.

BACKGROUND: Maternal prenatal psychiatric disease has been identified as a possible risk factor for atopic dermatitis development in her children. We quantified the associations between maternal and paternal psychiatric disease and the development of atopic dermatitis in their offspring using nationwide registries. METHODS: All children in Denmark born between 1 January 1996 and 31 December 2011 who developed atopic dermatitis prior to their fifth birthday were identified and individually matched 1:10 with controls from the general population and with children receiving care in a similar ambulatory/hospital setting. Conditional logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals. RESULTS: A total of 8602 children with atopic dermatitis were matched with controls. Rates of parental psychiatric care were similar in the atopic dermatitis and control groups. When compared to the general population, weak associations were found between childhood atopic dermatitis and maternal history of depression [OR 1.18 (95% confidence interval: 1.12-1.26)], alcohol abuse [OR 1.37 (1.17-1.60)] and illicit drug use [OR 1.34 (1.14-1.60)]. However, associations became insignificant when the paediatric ambulatory/hospital control group was used [OR 1.05 (0.99-1.13)], [OR 1.14 (0.98-1.34)] and [OR 1.03 (0.88-1.22)], respectively. No paternal psychiatric disease or prenatal maternal psychiatric disease associated with the AD development in the offspring. CONCLUSIONS: While we found no consistent associations between maternal or paternal psychiatric disease and the subsequent development of atopic dermatitis in their offspring, children of parents with substance abuse issues may be more likely to receive an atopic dermatitis diagnosis.

Atopic dermatitis is associated with anxiety, depression, and suicidal ideation, but not with psychiatric hospitalization or suicide.

BACKGROUND: Atopic dermatitis (AD) has been linked with psychiatric disease in adults. However, the exact relationship and its consequences have been insufficiently studied. Our aim of this study was to assess the association between depression, anxiety, and AD in adults and examine the risk of hospitalization and suicide. METHODS: We utilized questionnaire data from a large general population study with data on social habits and psychiatric symptoms to compare prevalences of depression, anxiety, suicidal ideation, and anxiety attacks, in adults with and without a history of AD. Additionally, we used nationwide hospital/clinic registry and prescription data to examine the risk of anxiety and depression in Danish adults with mild and moderate-severe AD, as well as the risk of hospitalization and suicide. RESULTS: In the general population study, those with AD reported clinician-diagnosed depression and anxiety more often than non-AD subjects, and had an increased prevalence of suicidal ideation and depressive symptoms. In the health registry study, moderate-severe AD patients had increased risk of antidepressant and anxiolytic medication use, while patients with mild AD only had increased risk of anxiolytic medication use. There was no increased risk of hospitalization or outpatient contacts due to depression or anxiety, or risk of suicide in AD patients. CONCLUSIONS: Depression, anxiety, and suicidal ideation are more common among AD individuals, but do not lead to psychiatric consultations, hospitalization, or suicide.

Poor agreement in questionnaire-based diagnostic criteria for adult atopic dermatitis is a challenge when examining cardiovascular comorbidity.

BACKGROUND: The association between atopic dermatitis (AD) and cardio-metabolic risk factors is not yet established. Furthermore, no validated questionnaire-based method of identifying adults with AD is currently available. OBJECTIVES: To assess the cardio-metabolic risk in adults with a history of AD using 3 different questionnaire-based diagnostic criteria. METHODS: We utilized data from a general population study including questionnaire data and objective measurements of 9656 Danish adults. To identify adults with a history of AD, we used a question regarding physician-diagnosed AD and 2 versions of the UK Working Party Diagnostic Criteria. Associations between AD status and cardio-metabolic endpoints were estimated using survey weighted logistic and linear regression analysis. RESULTS: We identified 462 (4.8%) adults with self-reported physician-diagnosed AD, whereas 903 (9.4%) and 226 (2.3%) had AD according to the UK Working Party Criteria when at least 2 and 3of 4 minor criteria were fulfilled. The populations were not comparable in terms of occurrence of cardio-metabolic risk factors. For example, the prevalence of obesity was lower in participants with physician-diagnosed AD but overall higher in UK 2/4 and UK 3/4. CONCLUSION: Due to the heterogeneity in the captured study populations in terms of the studied outcomes and absence of a gold standard, no conclusions regarding the cardio-metabolic risk in adults with AD in a general population could be made. This study serves as an example of the challenges that are often encountered in questionnaire-based epidemiologic studies and highlights the need of better definitions for this patient group.

Atopic dermatitis and alcohol use - a meta-analysis and systematic review.

While several maternal exposures have been associated with an increased risk of atopic dermatitis (AD) in offspring, the effect of alcohol use during pregnancy on the risk of AD in offspring is unclear. Furthermore, it is unclear whether adults with AD have an increased alcohol use, although other poor health behaviours have been associated with AD including smoking and physical inactivity as well as psychiatric disease. In this systematic review and meta-analysis, the association between alcohol use and AD was investigated in two ways: 1) whether alcohol use (drinkers versus abstainers) during pregnancy is associated with AD in offspring and 2) whether AD is associated with increased alcohol use. The medical databases PubMed, EMBASE and Web of Science were searched, and data extraction was carried out by two independent reviewers. Eighteen studies were included in the qualitative analysis (comparing alcohol drinkers to abstainers), and 12 studies were included in the quantitative analysis. There was a positive association between alcohol use during pregnancy and development of AD in offspring (pooled odds ratio [OR] 1.16; 95% confidence interval [CI] 1.09-1.24). However, there was no consistent association between AD in adults and adolescents and alcohol use (pooled OR 1.06; 95% CI 0.92-1.23). There is a need for future well-designed prospective studies to firmly establish the association between alcohol use and AD.

The effects of season and weather on healthcare utilization among patients with atopic dermatitis.

BACKGROUND: Patient-reported triggers for atopic dermatitis (AD) flares include changes in ultraviolet irradiation, humidity and temperature. OBJECTIVES: To identify the relationships between weather data and healthcare utilization in AD patients. METHODS: Using nationwide healthcare registries, clinic (1994-2012) and hospital visits (1977-2012) for AD treatment were calculated as well as monthly totals of topical corticosteroid (TCS) (1996-2012) and calcineurin inhibitor (TCI) prescriptions (2003-20012) filled by AD patients. We calculated monthly averages of temperature, atmospheric pressure, cloud cover and hours of bright sunlight and compared these variables to healthcare utilization endpoints, for the years 2000-2012 (n = 156 months), using linear regression models. RESULTS: In Denmark, between the year 2000 and 2012, mean monthly totals of AD emergency room visits were 6, AD hospitalizations 32, AD outpatient visits 170, TCS prescriptions filled by AD patients 3811 and TCI prescriptions 2552. Healthcare utilization among AD patients was highest in winter/spring. Temperature was the environmental variable that had the strongest association with healthcare utilization: per 1°C lower monthly temperature, 2 more (95% confidence interval [CI] 1-4) AD clinic/hospital visits hospitalizations were observed, 18 (95% CI 9-26) more TCS prescriptions and 53 (95% CI 36-70) more TCI prescriptions were filled by patients with AD. Environmental variables were highly correlated. Associations between AD healthcare utilization and hours of cloud cover were generally positive, while those with hours of bright sunlight were generally inverse. CONCLUSIONS: AD healthcare utilization markers changed significantly with season. A decline in temperature correlated well with AD patients' healthcare utilization, but a causative role could not be determined with certainty.

Computer-aided transrectal ultrasound: does prostate HistoScanning™ improve detection performance of prostate cancer in repeat biopsies?

BACKGROUND: An imaging tool providing reliable prostate cancer (PCa) detection and localization is necessary to improve common diagnostic pathway with ultrasound targeted biopsies. To determine the performance of transrectal ultrasound (TRUS) augmented by prostate HistoScanning(TM) analysis (PHS) we investigated the detection of prostate cancer (PCa) foci in repeat prostate biopsies (Bx). METHODS: 97 men with a mean age of 66.2 (44-82) years underwent PHS augmented TRUS analysis prior to a repeat Bx. Three PHS positive foci were defined in accordance with 6 bilateral prostatic sectors. Targeted Bx (tBx) limited to PHS positive foci and a systematic 14-core backup Bx (sBx) were taken. Results were correlated to biopsy outcome. Sensitivity, specificity, predictive accuracy, negative predictive value (NPV) and positive predictive value (PPV) were calculated. RESULTS: PCa was found in 31 of 97 (32%) patients. Detection rate in tBx was significantly higher (p < .001). Detection rate in tBx and sBx did not differ on patient level (p ≥ 0.7). PHS sensitivity, specificity, predictive accuracy, PPV and NPV were 45%, 83%, 80%, 19% and 95%, respectively. CONCLUSIONS: PHS augmented TRUS identifies abnormal prostatic tissue. Although sensitivity and PPV for PCa are low, PHS information facilitates Bx targeting to vulnerable foci and results in a higher cancer detection rate. PHS targeted Bx should be considered in patients at persistent risk of PCa.

[Endoprosthetic treatment of osteoporosis-related coxarthrosis : aspects of safe patient treatment]. / Endoprothetische Versorgung bei osteoporoseassoziierter Koxarthrose : Aspekte zur sicheren Patientenversorgung.

BACKGROUND: With increasing life expectancy the prevalence of osteoarthritis is also substantially rising. Patients aged between 65 and 75 years scheduled for total joint arthroplasty suffer from undetected osteoporosis in 20-25% of cases. OBJECTIVES: How to determine osteoporosis during preoperative workup? Which conclusions can be drawn for the operation treatment and the postoperative course? METHODS: The literature dealing with the prevalence of osteoporosis, perioperative complications of total hip arthroplasty, selected register informations, guidelines for diagnostics and treatment of osteoporosis and for the postoperative treatment are summarized and discussed. RESULTS: The fracture risk is determined according to the guidelines of the Dachverband Osteologie (DVO, Governing Body on Osteology). The implant and the anchorage are selected based on the risk of suffering from osteoporosis. An intraoperative fracture and early aseptic loosening are the main operative risk factors. For the postoperative course in addition to education about arthroplasty, adequate support for prevention of falls is mandatory. Continuous physiotherapy with muscular strengthening is advisable. The long-term medication should be checked for risks in the PRISCUS list of potentially inappropriate medication in the elderly and non-steroidal anti-inflammatory drugs (NSAIDs) should not be prescribed in patients with cardiac comorbidities. Patients with confirmed osteoporosis should be treated with antiresorptive agents.

Sentinel node biopsy in soft tissue sarcoma subtypes with a high propensity for regional lymphatic spread--results of a large prospective trial.

BACKGROUND: The role of sentinel lymph node biopsy (SLNB) in soft tissue sarcoma patients has yet to be determined. We sought to evaluate the role of SLNB in the treatment of patients with clear cell sarcoma (CCS), synovial sarcoma (SS), epithelioid sarcoma (ES) and rhabdomyosarcoma (RMS). PATIENTS AND METHODS: Sixty-two consecutive patients without history of regional lymphatic spread or evidence of distant metastases underwent SLNB. RESULTS: Positive sentinel nodes were identified in 2 out of 42 patients with SS and in 6 out of 12 patients with CCS. Only two CCS patients had further metastatic nodes in regional dissection. Both of these patients, along with another CCS patient, developed distant metastases and ultimately died of disease. The remaining three CCS patients are disease-free in follow-up. One patient with SS and another with ES developed regional lymph node metastases following a negative SLNB, while a further patient with RMS developed distant metastases followed by a local recurrence with regional metastases shortly after. CONCLUSIONS: SLNB is an important diagnostic tool for patients with CCS, who appear to have a high rate of clinically occult regional lymph node metastases at diagnosis. For SS patients, SLNB appears to be of very little relevance.

[Femoral nerve palsy as delayed complication after total hip replacement: delayed hematoma formation in unexpected screw malpositioning]. / Femoralisparese als Spätkomplikation nach Hüftendoprothesenimplantation: Späte Hämatombildung bei unerwarteter Schraubenfehllage.

Nerve injury after total hip replacement is a rare but severe complication. If the nerve lesion becomes evident in the early postoperative phase the lesion is often due to an incorrect implant position, direct nerve injury or vascular injury with manifestation of a hematoma which results in nerve compression. Secondary nerve lesions are more often due to a chronic hematoma with nerve compression. Secondary nerve lesions in particular are often a diagnostic challenge and should lead to an early revision after comprehensive imaging diagnostics.

Concentration variability of potent allergens of p-tert-butylphenol-formaldehyde resin (PTBP-FR) in patch test preparations and commercially available PTBP-FR.

BACKGROUND: p-tert-Butylphenol-formaldehyde resin (PTBP-FR) is a common component of glues used in the manufacturing of many plastic, electronic, rubber, wood and leather products. Two main allergens of PTBP-FR have been described. OBJECTIVES: To determine the concentrations of the two main allergens of PTBP-FR in diagnostic patch testing preparations and PTBP-FR available to glue and adhesive manufacturers. METHODS: Nuclear magnetic resonance spectrometry was used to confirm the identity and determine the purity of reference materials. High-pressure liquid chromatography was used to analyse patch test preparations and commercially available PTBP-FR. RESULTS: In the PTBP-FR in analysed patch test preparations the highest concentration of the allergenic dimer 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl)-6-hydroxymethylphenol found was 1·79% and the lowest 0·21%. The highest concentration of the allergenic dimer 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-benzyloxymethyl)-6-hydroxymethylphenol found in PTBP-FR of analysed patch test preparations was 0·50% and the lowest concentration found was 0·04%. In commercially available PTBP-FR the highest concentration of 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl)-6-hydroxymethylphenol found was 3·7% and the highest concentration of 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-benzyloxymethyl)-6-hydroxymethylphenol found was 1·1%. In three PTBP-FR samples neither allergen could be detected. CONCLUSIONS: Our data suggest that reporting resin concentration in petrolatum is not predictive of a consistent concentration of the two main allergens of PTBP-FR. The 10-fold difference in allergen concentration between different patch test preparations has significant ramifications for maintaining consistent dose of delivered allergen. The results of this study reinforce the need for patch test product standardization in the contact dermatitis community.

Nuclear factor of activated T cells mediates oxidised LDL-induced calcification of vascular smooth muscle cells.

AIMS/HYPOTHESIS: Vascular calcification is a prominent feature of both atherosclerosis and diabetes, and is clinically associated with osteoporosis. The expression of bone-regulatory factors and the impact of oxidative stress in aortic calcification are well-documented. Recently, nuclear factor of activated T cells (NFAT) cytoplasmic, calcineurin-dependent 1 (NFATc1) was identified in calcified aortic valves and has been implicated in vascular calcification. Therefore, we assessed the mechanisms of osteogenic transdifferentiation of vascular smooth muscle cells induced by oxidised LDL (oxLDL) and evaluated the role of NFAT in this process. METHODS: Human coronary artery smooth muscle cells (HCASMCs) were cultured for 21 days in medium supplemented with oxLDL. NFAT was inhibited using the NFAT inhibitor VIVIT, or by knockdown with small interfering RNA (siRNA). Osteogenic transdifferentiation was assessed by gene expression, matrix mineralisation and alkaline phosphatase activity. RESULTS: Exposure to oxLDL caused the transformation of HCASMCs towards an osteoblast-like phenotype based on increased mineral matrix formation and RUNX2 expression. NFATc1 blockade completely prevented oxLDL-induced osteogenic transformation of HCASMCs as well as oxLDL-induced stimulation of osteoblast differentiation. In contrast, matrix mineralisation induced by osteogenic medium was independent of the NFAT pathway. Of note, oxLDL-conditioned medium from HCASMCs transferred to bone cells promoted osteoblast mineralisation. Consistent with these in vitro findings, diabetic rats with a twofold increase in oxidised lipid levels displayed higher aortic calcium concentrations and increased expression of osteogenic markers and production of NFATc1. CONCLUSIONS/INTERPRETATION: Our results identify the NFAT signalling pathway as a novel regulator of oxLDL-induced transdifferentiation of vascular smooth muscle cells towards an osteoblast-like phenotype.

[Templating and radiological outcome monitoring for elective total hip arthroplasty. Applied quality management principles for safe patient care]. / Operationsplanung und Ergebniskontrolle in der elektiven Hüftendoprothetik. Angewandtes Qualitätsmanagement als Grundlage einer sicheren Patientenversorgung.

Implementation of total hip arthroplasty is a successful and reliable treatment for end-stage osteoarthritis. The biomechanics and components as well as the fixation were selected with the aid of templating. Based on a cohort of 114 patients the quality of digital X-rays and the operative results were determined. There was a slight leg lengthening and a good offset reconstruction in these patients. For the patients with replacement of the second hip the leg lengthening was smaller. The cup inclination was at 43° and 44° within the desired range. The prediction of the exact component size used was 40% for the cup and 29% for the stem.Through variation in scaling of the digital X-ray a diminishing prediction accuracy was found in our study. The correction of biomechanics and position of components showed good quality in patient care. Templating and assessment of the postoperative result in total hip arthroplasty is a model for continuous quality management and can be recommended for safe patient care.

[Symptomatic testicular metastasis of acinar adenocarcinoma of the prostate]. / Symptomatische Hodenmetastase eines azinären Adenokarzinoms der Prostata.

We report about the rare occurrence of symptomatic testicular metastasis of an acinar adenocarcinoma of the prostate. Testicular metastases are usually incidentally detected in patients treated with bilateral orchiectomy or more often during autopsy. In the literature, there are only a few clinical cases describing symptomatic testicular metastases. However, the possibility of such metastases should be considered in patients diagnosed with advanced prostate cancer. Testicular examination should be performed regularly, even in patients with low prostate-specific antigen levels.

[Multicenter comparison of complications after robot-assisted and open simple prostatectomy]. / Multizentrischer Vergleich von Komplikationen nach roboterassistierter und offen chirurgischer Prostataadenomenukleation.

INTRODUCTION: Robot-assisted simple prostatectomy (RASP) is a relatively new minimally invasive procedure for surgical treatment to manage symptomatic, therapy-refractory benign prostate hyperplasia (BPH) in prostate volumes >80 cm3. Thus, postoperative morbidity based on Clavien-Dindo and hematological parameters in RASP and open simple prostatectomy (OSP) procedures are examined. PATIENTS AND METHODS: We retrospectively reviewed a total of 78 patients: 39 patients underwent RAPS and 39 OSP. The following parameters were statistically evaluated and compared: age, PSA value, prostate volume, ASA score, duration of hospital stay, operative time, Hb decrease on postoperative (po) day 1 and in the 5 five po days, CRP peak in the first 5 po days and transfusion rate. RESULTS: The comparison between RASP and standard OSP showed no significant differences regarding the mean patient age (73 vs. 74 years; p =0.54), PSA values (7.7 vs. 10.7 ng/ml; p =0.17), ASA score (2.2 vs. 2.3; p =0.26) and prostate volume (130 vs. 113 cm3; p =0.07). Patients in the RAPAE group had statistically significant longer surgery (178 vs. 110 min; p =<0.01) with a significantly smaller decrease in Hb on po day 1 (1.9 vs. 3.3 g/dl; p ≤0.01) and in the first 5 po days (2.4 vs. 4.2 g/dl; p ≤0.01), lower need for preserved blood (3% vs. 26%; p =0.01) and number of blood bags (0.1 vs. 1.3; p =0.01), a lower po Clavien-Dindo score (0.44 vs. 1.23; p =0.003) and lower CRP values (52 vs. 104 mg/l; p ≤0.01) in the first 5 po days. CONCLUSION: RASP is a safe procedure that offers the advantage of reduced blood loss and blood bag consumption and rare complications due to the minimally invasive surgical method. The OSP group showed an increased occurrence of complications due to bleeding, leading to prolonged hospitalization and significantly increased need for blood transfusion. The lesser increase of CRP in RASP group is a result of the lower invasiveness of the robot-assisted procedure.

Equipment-independent reference values for dopamine transporter imaging with 123I-FP-CIT.

AIM: Reliable reference values are helpful to interpret and compare the results of dopamine transporter imaging with SPECT. Since semi-quantitative reference values cannot be easily transferred between imaging equipments, this study aimed to establish equipment independent normal values for the true striatal binding of 123I-FP-CIT. PATIENTS, METHODS: Specific striatal FP-CIT binding of 6 healthy volunteers and 26 patients with essential tremor were used to generate a reference range by applying an equipment specific resolution dependent factor to compensate for recovery effects. This factor has been determined previously by a series of standardized phantom measurements of an anthropomorphic basal ganglia phantom. Herewith, the resulting DAT binding values represent the expected true specific binding in the striatum. RESULTS: On average, true specific striatal binding was 5.83 +/- 0.96 in healthy controls, 5.25 +/- 0.67 in patients with essential tremor and 5.36 +/- 0.75 in the entire study cohort. CONCLUSION: These preliminary results may serve as a basis for the generation of a generally accepted equipment independent reference range for dopamine transporter imaging with 123I-FP-CIT. By a simple phantom measurement that can be accomplished within one day factors related to specific imaging equipment and processing can be corrected for, resulting in specific binding values which may enable a more standardized interpretation of dopamine transporter scans.

Conservation of a tRNA core for aminoacylation.

The core region of Escherichia coli tRNA(Cys)is important for aminoacylation of the tRNA. This core contains an unusual G15:G48 base pair, and three adenosine nucleotides A13, A22 and A46 that are likely to form a 46:[13:22] adenosine base triple. We recently observed that the 15:48 base pair and the proposed 46:[13:22] triple are structurally and functionally coupled to contribute to aminoacylation. Inspection of a database of tRNA sequences shows that these elements are only found in one other tRNA, the Haemophilus influenzae tRNA(Cys). Because of the complexity of the core, conservation of sequence does not mean conservation of function. We here tested whether the conserved elements in H. influenzae tRNA(Cys)were also important for aminoacylation of H. influenzae tRNA(Cys). We cloned and purified a recombinant H. influenzae cysteine-tRNA synthe-tase and showed that it depends on 15:48 and 13, 22 and 46 in a relationship analogous to that of E. coli cysteine-tRNA synthetase. The functional conservation of the tRNA core is correlated with sequence conservation between E.coli and H.influenzae cysteine-tRNA synthetases. As the genome of H. influenzae is one of the smallest and may approximate a small autonomous entity in the development of life, the dependence of this genome on G15:G48 and its coupling with the proposed A46:[A13:A22] triple for aminoacylation with cysteine suggests an early role of these motifs in the evolution of decoding genetic information.