Application of Risk-Based Cancer Screening in Patients With Dermatomyositis.

This cohort study investigates the performance of the International Myositis Assessment and Clinical Studies Group cancer screening recommendations in a community setting.

Area Deprivation and Disease Severity in Adult Patients With Discoid Lupus Erythematosus.

Importance: The association of area deprivation with outcomes in discoid lupus erythematosus (DLE) remains poorly understood. Objective: To determine the association between US Census block measures of deprivation and disease severity in adult patients with DLE. Design, Setting, and Participants: This cross-sectional study included 154 patients with DLE seen between January 1, 2007, and January 1, 2024, at a single-center referral-based specialty rheumatologic-dermatology clinic in Philadelphia, Pennsylvania. Patients were aged 18 to 73 years and were enrolled in the University of Pennsylvania's Cutaneous Lupus Erythematosus Database study. Data were analyzed between January 1, 2024, and May 8, 2024. Exposures: Residence in a highly disadvantaged area as geocoded by a state area deprivation index (ADI). Main Outcomes and Measures: The main outcome was DLE disease severity as codified by the validated Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) damage and activity scores. Results: A total of 154 adult patients with DLE (128 women [83%] and 26 men [17%]; mean [SD] age, 43 [13] years; 6 [4%] Asian individuals, 98 [64%] Black individuals, 2 [1%] Hispanic individuals, 46 [30%] White individuals, and 2 individuals [1%] with other race or ethnicity; 78 [51%] with an ADI >5; 43 who currently smoked [28%];and 56 [36%] with concurrent systemic lupus erythematosus) were included in the analysis. By multivariable logistic regression, residence within communities with an ADI greater than 5 was associated with nearly 4-fold greater odds of moderate to severe damage (odds ratio [OR], 3.90; 95% CI, 1.27-12.69] and activity (OR, 3.31; 95% CI, 1.27-9.44). Concurrent cigarette smoking was similarly associated with greater odds of moderate to severe damage (OR, 3.15; 95% CI, 1.09-10.29). After controlling for ADI and other confounders, race was not significantly associated with DLE disease severity. Conclusions and Relevance: The results of this cross-sectional study suggest that geospatial disadvantage is associated with DLE disease severity independent of race. This invites a paradigm shift that considers the social context within which racial disparities are observed, highlighting the potential for geographically targeted interventions and policy changes to improve patient outcomes in DLE.

The Histone Demethylase HR Suppresses Breast Cancer Development through Enhanced CELF2 Tumor Suppressor Activity.

The hairless (HR) gene encodes a transcription factor with histone demethylase activity that is essential for development and tissue homeostasis. Previous studies suggest that mutational inactivation of HR promotes tumorigenesis. To investigate HR mutations in breast cancer, we performed targeted next-generation sequencing using DNA isolated from primary breast cancer tissues. We identified HR somatic mutations in approximately 15% of the patient cohort (n = 85), compared with 23% for BRCA2, 13% for GATA3, 7% for BRCA1, and 3% for PTEN in the same patient cohort. We also found an average 23% HR copy number loss in breast cancers. In support of HR's antitumor functions, HR reconstitution in HR-deficient human breast cancer cells significantly suppressed tumor growth in orthotopic xenograft mouse models. We further demonstrated that HR's antitumor activity was at least partly mediated by transcriptional activation of CELF2, a tumor suppressor with RNA-binding activity. Consistent with HR's histone demethylase activity, pharmacologic inhibition of histone methylation suppressed HR-deficient breast cancer cell proliferation, migration and tumor growth. Taken together, we identified HR as a novel tumor suppressor that is frequently mutated in breast cancer. We also showed that pharmacologic inhibition of histone methylation is effective in suppressing HR-deficient breast tumor growth and progression.

Resection of retroperitoneal tumors with inferior vena cava involvement without caval reconstruction.

BACKGROUND AND OBJECTIVES: Retroperitoneal tumors with involvement of the inferior vena cava (IVC) often require resection of the IVC to achieve complete tumor removal. This study evaluates the safety and efficacy of IVC ligation without caval reconstruction. METHODS: A retrospective chart review of patients who underwent IVC ligation (IVC-Ligation) and IVC resection with reconstruction (IVC-Reconstruction) at our institution between May 2004 and April 2021 was performed. Outcomes from the two surgical techniques were compared via univariate analysis using the Kruskal-Wallis test for continuous variables and Fisher's exact test for categorical variables. RESULTS: Forty-nine IVC-Ligation and six IVC-Reconstruction surgeries were identified. There were no differences in baseline demographics, tumor characteristics, complication rates, postoperative morbidity, or overall 5-year survival between groups. IVC-Reconstruction patients were more likely to require intensive care unit admission (83% vs. 33%; p = 0.0257) and the IVC-Ligation cohort had a tendency to present with nondebilitating postoperative lymphedema (35% vs. 0%; p = 0.1615), which resolved for most patients. CONCLUSIONS: IVC-Ligation is a viable surgical option for select patients presenting with retroperitoneal tumors with IVC involvement and provides acceptable short- and medium-term outcomes.

Prospective, Randomized Comparison of Dual-Lumen vs Single-Lumen Flexible Ureteroscopes in Proximal Ureteral and Renal Stone Management.

Introduction: We sought to compare the safety, efficacy, efficiency, and surgeon experience during upper urinary tract stone management with single-lumen (SLFU) vs dual-lumen flexible ureteroscopes (DLFU). Materials and Methods: Seventy-nine patients with proximal ureteral or renal stone burden <2 cm were randomized to a SLFU or DLFU. We recorded times for ureteroscopy (URS), laser lithotripsy, stone basketing, as well as intraoperative and postoperative complications. The rate of stone clearance and stone free status were calculated using CT imaging. Surgeons completed a survey after each procedure rating various metrics regarding ureteroscope performance. Results: Thirty-five patients from the single-lumen group and 44 patients from the dual-lumen group had comparable median URS time (37 vs 35 minutes, p = 0.984) and basketing time (12 vs 19 minutes; p = 0.584). Median lithotripsy time was decreased in the dual-lumen group (single: 6 vs dual: 2 minutes, p = 0.017). The stone clearance rate was superior in the dual-lumen group (single: 3.7 vs dual: 7.1 mm3/min, p = 0.025). The absolute stone-free rate (SFR) was superior for the dual-lumen group (single: 26% vs dual: 48%, p = 0.045). No differences in intraoperative (single: 0% vs dual: 2%; p = 0.375) and postoperative complications (single: 7% vs dual: 11%, p = 0.474) were observed. Surgeons' ratings of the dual-lumen ureteroscope was superior for visibility, comfort, ease of use, and overall performance. Conclusions: The use of the dual-lumen ureteroscope in patients with renal and proximal ureteral stones <2 cm provided shorter lithotripsy time, higher stone clearance rates, improved SFR, and superior surgeon ratings when compared with SLFUs.

Multidisciplinary Approach and Outcomes of Pretreatment Small (cT1a) Renal Mass Biopsy: Single-Center Experience.

Purpose: We evaluated our experience of a multidisciplinary approach to renal mass biopsy (RMB) for small renal masses (SRMs) employing in-office ultrasound (US)-guided biopsy by urology (24%), CT, or US biopsy by interventional radiology (IR) (79%), and endoscopic ultrasound (EUS)-guided biopsy by gastroenterology (GI) (4%). Materials and Methods: A single-institution retrospective review of patients who underwent RMB for SRM from May 2013 to August 2019 was conducted. Data regarding patient demographics, tumor characteristics, biopsy technique, histopathology, and management were collected. Diagnostic rates, concordance with final pathology, complications, and outcomes were analyzed. Results: Of the 192 biopsies reviewed, 63% biopsies were malignant, 20% were benign, and 17% were nondiagnostic. Based on biopsy results, 71 patients (37%) elected active surveillance. Thirty-eight (20%) patients underwent cryoablation, 56 (29%) underwent partial nephrectomy, 14 (7%) underwent radical nephrectomy, and the remaining patients were treated elsewhere. The rate of surgery for benign pathology after pretreatment RMB was 3%. The concordance rate between biopsy and final pathology was 99% for malignancy, 96% for specific pathology subtype, and 85% for renal cell carcinoma grade. Median time from diagnosis to definitive treatment was 97 days (urology: 76, IR: 110 and GI: 54, p = 0.002). Three (1.6%) Clavien I complications were reported. Conclusion: Our multidisciplinary approach to RMB for clinical stage T1a demonstrated favorable safety and diagnostic rates, which effectively directed management strategies and minimized surgery for benign disease. Urologist-performed office biopsies significantly shortened the time from diagnosis to definitive treatment. Our experience with GI EUS biopsy has demonstrated feasibility and safety for tumors that were otherwise not accessible percutaneously.

Crowd-Sourced Assessment of Surgical Skills of Urology Resident Applicants: Four-Year Experience.

OBJECTIVE: To determine a) if surgical skills among urology resident applicants could be reliably assessed via crowdsourcing and b) to what extent surgical skills testing impacts resident selection. DESIGN: Interviewees completed the following surgical skills tasks during their interview day: open knot tying (OKT), laparoscopic peg transfer (LPT), and robotic suturing (RS). Urology faculty and crowd-workers evaluated each applicant's video-recorded performance using validated scoring and were assessed for agreement using Cronbach's alpha. Applicants' USMLE scores, interview scores, and Jefferson Scale of Physician Empathy (JSPE-S) scores were assessed for correlation with skills testing scores and match rank. Additionally, a survey was distributed to interviewees assessing match outcomes. SETTING: University of California Irvine Department of Urology, Surgical Skills Laboratory PARTICIPANTS: All 94 urology residency interviewees at the University of California Irvine Department of Urology from 2015-2018 were invited to complete the three surgical skills tasks on their interview day. RESULTS: Survey responses were received from all 94 interviewees (100%). Crowd and expert agreement was good (α=0.88), fair (α=0.67), and poor (α=0.32) for LPT, RS, and OKT scores, respectively. The skills testing scores did not correlate with match rank, USMLE score, or JSPE-S score. On multivariate analysis, only interview score (r= -0.723; p<0.001) and faculty LPT score (r=-0.262; p=0.001) were significant predictors of match rank. Interviewees who reported matching into a top 3 residency choice had significantly higher faculty LPT scores than those who did not (11.9 vs. 9.7, p=0.03). CONCLUSIONS: Surgical skills overall did not significantly impact match rank. Expert assessment of laparoscopic peg transfer skills and interview performance among urology resident applicants correlated with match rank.

Comparison of Conventional and Triple Bolus Computerized Tomographic Urography Protocols for Radiation Dose Reduction in Hematuria Evaluation: A Randomized Controlled Trial.

PURPOSE: Computerized tomographic urography is the diagnostic tool of choice for evaluating hematuria. In keeping with the ALARA (As Low As Reasonably Achievable) principle, we evaluated a triple bolus computerized tomography protocol designed to reduce radiation exposure. MATERIALS AND METHODS: Patients with macroscopic or microscopic hematuria were prospectively randomized to conventional computerized tomography (100) or triple bolus computerized tomography (100). The triple bolus computerized tomography protocol entails 2 scans: pre-contrast scan followed by 3 contrast injections at 40 seconds, 60 seconds and 20 minutes prior to the second scan to capture all 3 phases. The conventional computerized tomography protocol requires 4 scans: pre-contrast scan, and 3 post-contrast scans at the corticomedullary, nephrographic and excretory phases. Radiation exposure and the detection of urological pathology were recorded based on radiology reports. RESULTS: There were no differences in patient demographics or body mass index between the 2 groups. Triple bolus computerized tomography exposed patients to 33% less radiation (1,715 vs 1,145 mGy*cm for conventional vs triple bolus computerized tomography; p <0.001). For macroscopic hematuria, the pathology detection rates were 70% for triple bolus and 73% for conventional computerized tomography (p=0.72). For microscopic hematuria, the detection rates were 59% for triple bolus and 50% for conventional computerized tomography (p=0.68). In both groups, the rates of detection of urolithiasis, renal cysts, urological masses, bladder pathology and prostate pathology were no different between triple bolus and conventional computerized tomography. CONCLUSIONS: In both the settings of macroscopic and microscopic hematuria evaluation, triple bolus computerized tomography significantly reduces radiation exposure while providing equivalent detection of genitourinary pathology compared to conventional computerized tomography. The ability to detect upper tract filling defects was not specifically tested.

Evaluation of a Novel Female Gender Flexible Ureteroscope: Comparison of Flow and Deflection to a Standard Flexible Ureteroscope.

Introduction: The advent of single-use disposable flexible ureteroscopes allows for rapid prototyping of novel endoscopes. In this regard, we sought to develop a female-specific ureteroscope, with a shorter working length, to account for the female anatomy. We hypothesized that the shorter, female-specific single-use flexible ureteroscope would engender higher irrigation flow at a given pressure than that of the standard-length ureteroscope. Methods: An in vitro analysis of a standard 65 cm Dornier Axis™ ureteroscope and a shorter, 45 cm female-specific Dornier Axis ureteroscope was performed. All other aspects of the endoscopes were identical. Each ureteroscope was oriented vertically and connected to a Thermedx® irrigation system to provide uniform pressurized flow. The average flow rate was computed over five, 2-minute periods at pressure settings of 50, 100, 150, and 200 mm Hg. Data were collected with the working channel unoccupied, after placement of a 200 µm (0.6F) holmium laser fiber and after passage of a 1.7F stone basket. The procedure was then repeated with the endoscopes at maximum deflection. Results: The female gender ureteroscope had significantly higher irrigation flow rates than the standard-length ureteroscope under all conditions by an average of 11% (p < 0.02). The highest average percent increase, 17% (p < 0.001), was seen with the 1.7F NGage® basket in the working channel with the endoscope straight. The maximum angle of deflection was not significantly different between the female gender and standard ureteroscopes with an open working channel (314° vs 315°, p = 0.86), with the 1.7F NGage basket in place (314° vs 315°, p = 0.15), and with the 200 µm holmium laser in place (316° vs 309°, p = 0.09). Conclusions: A 45 cm female gender ureteroscope allows for a higher irrigation flow rate than the standard-length ureteroscope under all test conditions. There is no added benefit with regard to deflection capabilities.

Long-Term Antibiotic Treatment Prior to Laparoscopic Nephrectomy for Xanthogranulomatous Pyelonephritis Improves Postoperative Outcomes: Results from a Multicenter Study.

PURPOSE: Xanthogranulomatous pyelonephritis is a destructive bacterial infection typically necessitating nephrectomy. We hypothesized that long-term preoperative antibiotics would facilitate laparoscopic nephrectomy by reducing the renal inflammation. MATERIALS AND METHODS: We reviewed the records of all patients with histologically confirmed xanthogranulomatous pyelonephritis at 3 University of California institutions between 2005 and 2018. Patients were stratified by antibiotic treatment duration and surgical approach. Patients treated with long-term preoperative antibiotics (28 days or more of continuous treatment until surgery) were compared to patients treated with short-term antibiotics (less than 28 days) and those who only received single-dose prophylactic antibiotics before surgery. Patient demographics and operative outcomes were analyzed. Complications were assigned by Clavien-Dindo classification. RESULTS: Among the 61 patients, 51 (84%) were female and mean age was 50 years. There were 21 (34%) open procedures and 40 (66%) laparoscopic procedures. Median duration of antibiotic treatment was 5 days in those who received a short-term treatment and 87 days in those who received long-term treatment. Eleven patients received only prophylactic single-dose antibiotics. Using multivariate analysis among patients undergoing laparoscopic nephrectomy, controlling for preoperative drainage, long-term antibiotics resulted in a 6.5-day shorter length of stay (p=0.023) and less overall as well as milder postoperative complications (p <0.001). CONCLUSIONS: Greater than or equal to 4 weeks of preoperative antibiotics before laparoscopic nephrectomy for xanthogranulomatous pyelonephritis was associated with shorter length of stay and fewer, less severe postoperative complications.

Analysis of Ureteral Diameter and Peristalsis in Response to Irrigant Fluid Temperature Changes in an In Vivo Porcine Model.

Objective: It has been previously reported that warming irrigation fluid higher than body temperature may decrease ureteral spasm and thereby facilitate ureteroscopic access to the proximal ureter. Our objective was to examine the effects on ureteral peristalsis and ureteral diameter if the irrigant was warmed to just under the biological threshold for injury. Materials and Methods: Two female adult Yorkshire pigs were studied in this pilot study. In the first pig, a dilute mixture of contrast and irrigation fluid at 37°C and then at 43°C was instilled for 30 minutes into each renal pelvis through a ureteral catheter at 40 mm Hg. Retrograde pyelogram images were captured for each trial and the caliber of the ureter was measured using Vitrea® software. In the second pig, a lumbotomy was performed, and a magnetic sensor was placed on the extraluminal surface of the ureter to monitor ureteral peristalsis while repeating the aforedescribed regimen. Thirty minutes after the first regimen, the force exerted during placement of a 16F ureteral access sheath (UAS) was recorded at both temperatures using the University of California, Irvine Ureteral Force Sensor. Results: There was no statistically significant difference in ureteral caliber along the length of the ureter at 43°C (p = 0.87, p = 0.32, p = 0.66 for proximal, middle, and distal ureter, respectively). Indeed, there was an increase in peristalsis from baseline with fluid irrigation at 37°C and at 43°C (59% and 65%, respectively). There was no significant difference in the force exerted for UAS placement at either temperature. On histologic analysis, there were no significant changes in ureteral histology or luminal diameter. Conclusions: In a porcine model, warming irrigation fluid to just under the biological threshold for injury did not increase ureteral caliber, decrease ureteral peristalsis, or facilitate UAS placement. As such, during ureteroscopy, we continue to warm our irrigation fluid just to body temperature.

Outcomes in Patients with Renal Cell Carcinoma Undergoing Inferior Vena Cava Ligation without Reconstruction versus Thrombectomy: A Retrospective, Case Controlled Study.

PURPOSE: Radical nephrectomy with tumor thrombectomy is considered standard of care in patients with renal cell carcinoma. However, surgical ligation and interruption of the inferior vena cava is sometimes necessary when the tumor thrombus invades the inferior vena cava wall. This study assesses the outcomes in patients with renal cell carcinoma undergoing inferior vena cava ligation compared to inferior vena cava thrombectomy. MATERIALS AND METHODS: We conducted a case controlled, retrospective study at a high volume single-center institution. All patients with renal cell carcinoma who underwent ligation without reconstruction were matched with patients undergoing thrombectomy in a 1:2 ratio based on preoperative renal function, renal cell carcinoma stage and intraoperative thrombus level. Endpoints were complications, change in renal function and mortality. RESULTS: A total of 26 patients with renal cell carcinoma who underwent inferior vena cava ligation between 2005 and 2019 were matched with 52 patients who underwent inferior vena cava thrombectomy in the same time period. When compared to thrombectomy, patients undergoing ligation had higher 90-day readmission rate (19% vs 4%, p=0.025). The ligation group also had a higher postoperative complication rate (73% vs 39%, p=0.004) and higher rates of lymphedema (23% vs 8%, p=0.055). However, by 1-month followup the rate of persistent overall and major complications for both ligation and thrombectomy groups were comparable at 49% vs 31% (p=0.497) ad 8% vs 8% (p=1.000), respectively. Importantly, at 18-month followup, mean estimated glomerular filtration rate declines were similar between ligation group (8.5 ml/min/1.73 m2) and thrombectomy group (9.9 ml/min/1.73 m2; p=0.834). Differences in cancer-specific mortality (p=0.993) and all-cause mortality (p=0.756) were also not statistically significant. CONCLUSIONS: The outcomes of inferior vena cava ligation compared to inferior vena cava thrombectomy for renal cell carcinoma are similar. Patients with inferior vena cava ligation initially face a more complicated postoperative course but in the longer term have similar renal function recovery, complication rates and survival.

Biomarker function of HMGA2 in ultraviolet-induced skin cancer development.

The high mobility group AT-hook 2 (HMGA2) gene encodes a transcription factor that is expressed during embryonic development but down-regulated in adult tissues. Its re-expression in adult tissues is often associated with tumorigenesis. In this study, we found that HMGA2 is highly expressed in human cutaneous squamous cell carcinoma (SCC) cell lines and primary SCC tumors, but not in adjacent normal skin. In non-ultraviolet (UV)-irradiated mouse skin, baseline Hmga2 expression was detected in the epidermis but not in hair follicles. Following chronic UV exposure, we found activation of Hmga2 in hair follicles. UV-induced mouse skin SCC tumors displayed a ubiquitous increase in Hmga2 expression compared to non-tumor-bearing adjacent skin. In human SCC cells, decreased HMGA2 expression was linked with reduced cell proliferation following depletion of FOXM1 and TRIP13, two UV master regulator genes. Taken together, these findings highlight an important biomarker function of HMGA2 expression in UV-induced skin tumorigenesis and cell proliferation.

Evaluation of Interactive Virtual Reality as a Preoperative Aid in Localizing Renal Tumors.

Introduction: A detailed understanding of renal tumor anatomy is required to perform partial nephrectomy. We evaluated the utility of a CT-based interactive virtual reality (iVR) display to assist surgeons' understanding of the precise location of the renal tumor. Methods: CT scans and iVR models of 11 patients with a mean R.E.N.A.L. nephrometry score of 6.9 were evaluated. Seven faculty urologists and six urology residents reviewed CT scans and positioned each tumor onto a digital three-dimensional model of the same kidney, although without the tumor present. A week later, participants repeated the session using both iVR models and CT scans. For both time points, the overlap between the surgeon-inserted tumor and the actual tumor location was calculated. Participants answered a 1 to 10 Likert scale survey to gauge their understanding of renal and tumor anatomy based on CT alone vs CT+iVR. Results: Median tumor overlap for the entire cohort was 28% after CT review and 42% after CT+iVR (p = 0.05); among faculty urologists, for CT+iVR vs CT alone, percentage overlap improved (47% vs 33%, p = 0.033) and the incidence of 0% overlap decreased (19%-4%, p = 0.024), respectively. Among residents, there was no significant difference for either percentage overlap or 0% overlap for CT vs CT+iVR. The percentage overlap for the two tumors with high R.E.N.A.L. nephrometry scores (i.e., 10) increased from 51% to 67% after using CT+iVR (p = 0.039). The combination of CT+iVR was an independent predictor of improved overlap vs CT alone (odds ratio 2.22, 95% confidence interval 1.04-4.78, p = 0.039). Faculty surgeons' survey responses showed an improved understanding of the tumor location and shape with the addition of iVR (p < 0.05). Conclusions: The addition of patient-specific iVR models to standard CT imaging improved the ability of faculty urologists to accurately configure the location of a renal tumor, and improved their understanding of tumor anatomy.

Thrombocytopenia Preceding Urosepsis in an Otherwise Asymptomatic Patient After Bilateral Retrograde Intrarenal Surgery.

Introduction and Background: Urosepsis is commonly predicted by the systematic inflammatory response syndrome (SIRS) criteria. We report a case of urosepsis preceded only by thrombocytopenia. Case Presentation : An 80-year-old Caucasian female presented with recurrent urinary tract infections, type 1 second-degree heart block (Mobitz I), and chronic deep venous thrombosis for which she was taking apixaban. Computed tomography (CT) revealed a 1.3 cm right upper pole calculus (Hounsfield units (HU) = 704) and a left 5 mm nonobstructing interpolar calculus (HU = 904). A preoperative urine culture was sterile as the patient was on antibiotics. While on antibiotic coverage, the patient underwent bilateral retrograde intrarenal surgery with bilateral stent placement: the procedure time was 188 minutes. She was continued on vancomycin and gentamicin immediately postoperatively. On postoperative day (POD) 1, she was feeling well; her vital signs were within normal limits. However, the hemoglobin and the platelet counts declined from 12.4 to 10.0 g/dL and from 215 to 58/mm3, respectively. Because of the unexplained thrombocytopenia, the patient was kept at the hospital. In the afternoon, she became hypotensive (78/37 mm Hg) and a rapid response was called. She was admitted to the surgical intensive care unit and antibiotics were broadened. On POD 2, the patient met sepsis SIRS criteria with white blood cell (WBC) of 2.9/mm3 and heart rate of 92 bpm. Stone culture was positive for methicillin-resistant Staphylococcus aureus (MRSA). On POD 3, her blood pressure had returned to 116-142/47-84. On POD 5, platelet count recovered to 94/mm3 and WBC to 3.8/mm3. She was discharged on POD 6 with a 2-week ongoing course of intravenous vancomycin. On follow-up 7 weeks postoperatively, she was asymptomatic with WBC of 6.5/mm3 and platelet count of 206/mm3. Follow-up CT demonstrated normal renal anatomy with subcentimeter calculi clustered within the left renal parenchyma and no stones on the right side. Conclusion: This case shows an uncommon non-SIRS presentation of postoperative urosepsis signaled only by thrombocytopenia.

The transcriptome and its translation during recovery from cell cycle arrest in Saccharomyces cerevisiae.

Complete genome sequences together with high throughput technologies have made comprehensive characterizations of gene expression patterns possible. While genome-wide measurement of mRNA levels was one of the first applications of these advances, other important aspects of gene expression are also amenable to a genomic approach, for example, the translation of message into protein. Earlier we reported a high throughput technology for simultaneously studying mRNA level and translation, which we termed translation state array analysis, or TSAA. The current studies test the proposition that TSAA can identify novel instances of translation regulation at the genome-wide level. As a biological model, cultures of Saccharomyces cerevisiae were cell cycle-arrested using either alpha-factor or the temperature-sensitive cdc15-2 allele. Forty-eight mRNAs were found to change significantly in translation state following release from alpha-factor arrest, including genes involved in pheromone response and cell cycle arrest such as BAR1, SST2, and FAR1. After the shift of the cdc15-2 strain from 37 degrees C to 25 degrees C, 54 mRNAs were altered in translation state, including the products of the stress genes HSP82, HSC82, and SSA2. Thus, regulation at the translational level seems to play a significant role in the response of yeast cells to external physical or biological cues. In contrast, surprisingly few genes were found to be translationally controlled as cells progressed through the cell cycle. Additional refinements of TSAA should allow characterization of both transcriptional and translational regulatory networks on a genomic scale, providing an additional layer of information that can be integrated into models of system biology and function.