Search

The genetic architecture of atrial fibrillation (AF) encompasses low impact, common genetic variants and high impact, rare variants. Here, we characterize a high impact AF-susceptibility allele, KCNQ1 R231H, and describe its transcontinental geographic distribution and history. Induced pluripotent stem cell-derived cardiomyocytes procured from risk allele carriers exhibit abbreviated action potential duration, consistent with a gain-of-function effect. Using identity-by-descent (IBD) networks, we estimate the broad- and fine-scale population ancestry of risk allele carriers and their relatives. Analysis of ancestral migration routes reveals ancestors who inhabited Denmark in the 1700s, migrated to the Northeastern United States in the early 1800s, and traveled across the Midwest to arrive in Utah in the late 1800s. IBD/coalescent-based allele dating analysis reveals a relatively recent origin of the AF risk allele (~5000 years). Thus, our approach broadens the scope of study for disease susceptibility alleles to the context of human migration and ancestral origins., Many rare high-impact variants have been associated with disease, but the origins and functional impact are not always explored. Here, the authors trace the ancestry of a rare high impact atrial fibrillation allele in KCNQ1, and use iPSC-derived cardiomyocytes to characterize the effect of the allele.

Background: Cognitive impairment after sepsis is an important clinical problem. Determinants of postseptic cognitive impairment are not well understood. We thus undertook a systems biology approach to exploring a possible role for apolipoprotein E (APOE) in postseptic cognitive impairment. Design: Prospective, observational cohort. Setting: Intermountain Medical Center, a tertiary referral center in Utah. Patients/Participants: Patients with sepsis admitted to study intensive care units. Interventions: None. Methods: We obtained peripheral blood for deep sequencing of RNA and followed up survivors at 6 months with a battery of cognitive instruments. We defined cognitive impairment based on the 6-month Hayling test of executive function. In our primary analysis, we employed weighted network analysis. Secondarily, we compared variation in gene expression between patients with normal versus impaired cognition. Measurements and Main Results: We enrolled 40 patients, of whom 34 were follow-up eligible and 31 (91%) completed follow-up; 1 patient’s RNA sample was degraded—the final analytic cohort was 30 patients. Mean Hayling test score was 5.8 (standard deviation 1.1), which represented 20% with impaired executive function. The network module containing APOE was dominated by low-expression genes, with no association on primary analysis ( P = .8). Secondary analyses suggested several potential lines of future investigation, including oxidative stress. Conclusions: In this prospective pilot cohort, executive dysfunction affected 1 in 5 survivors of sepsis. The APOE gene was sparsely transcribed in peripheral leukocytes and not associated with cognitive impairment. Future lines of research are suggested.

Tension-type headache (TTH) - also known as 'regular' or 'ordinary' headache - is extremely common. The key symptom is a tight band or pressing pain felt on both sides of the head. The headache pain in TTH is mild or moderate and lasts from several hours up to a few days. TTH usually responds well to treatment with simple over-the-counter (OTC) analgesics such as ibuprofen and paracetamol.

Seclusion has become a contentious practice and initiatives have commenced to reduce or eliminate its use. This paper presents the initiatives that were introduced during a seclusion reduction project that was undertaken at an Australian forensic hospital. These initiatives are based on the six core strategies that have been successfully used in North America to reduce seclusion. However, there are challenges (patient characteristics, prisoner culture and ensuring safety) and opportunities (longer admissions, higher staff-patient ratio, staff confidence, sound risk assessment and management) that can influence projects to reduce seclusion in a forensic hospital. During this project, the frequency (mainly multiple seclusions of patients) and duration of seclusion events were reduced but there was less reduction in the number of patients that were secluded. It is possible that the strategies were successfully supported by the identified opportunities to reduce the frequency and duration of seclusion but the challenges were significantly powerful in the early period of admission to prompt the need for seclusion. Reducing seclusion in a forensic hospital is a complex undertaking as nurses must provide a safe environment while dealing with volatile patients and may have little alternative at present but to use seclusion after exhausting other interventions.

SummaryUrinary incontinence remains a topic that both patients and clinicians find difficult to discuss and manage. Following the NICE guidance published in 2006, a well-defined structure for the management of urinary problems was outlined. Conservative measures are the mainstay for all patients, with anticholinergic drugs playing a major role in the management of over-active bladder and urge incontinence.Surgical management is an area that continues to grow and develop. The types of procedures offered to patients have changed dramatically in the last 10–15 years, with the advent of tension-free vaginal tapes and more recently the use of botulinum toxin. It is important that health professionals encountering patients with incontinence are aware of the common urological/gynaecological operations available, the place of surgical options in the overall pathway, and the benefits as well as the risks associated with continence surgery. This article provides the non-specialist with an overview of the available surgical options for management of continence.

It is well accepted that influenza A virus predisposes individuals to often more severe superinfections with Streptococcus pneumonia. However, the mechanisms that lead to this synergy are not clearly understood. Recent data suggests that competent Th17 immunity is crucial to clearance and protection from invasive pneumococcal disease of the lung. We demonstrate that early influenza infection significantly reduced levels of pneumococcus driven IL-12p70, IL-23 and IL-27 in human monocytes with significant impairment of IL-17A and IFN-γ in HKSP-treated allogeneic mixed lymphocyte cultures. We also provide evidence to suggest that the hemagglutinin component of the virus is at least partially responsible for this downward pressure on IL-17 responses but surprisingly this suppression occurs despite robust IL-23 levels in hemagglutinin-treated monocyte cultures. This study demonstrates that influenza can directly affect the immunological pathways that promote appropriate responses to Streptococcus pneumonia in human immune cells. Importance Influenza virus is highly contagious and poses substantial public health problems due to its strong association with morbidity and mortality. Approximately 250,000–500,000 deaths are caused by seasonal influenza virus annually, and this figure increases during periods of pandemic infections. Most of these deaths are due to secondary bacterial pneumonia. Influenza-bacterial superinfection can result in hospitalisation and/or death of both patients with pre-existing lung disease or previously healthy individuals. The importance of our research is in determining that influenza and its component haemagglutinin has a direct effect on the classic pneumococcus induced pathways to IL-17A in our human ex vivo model. Our understanding of the mechanism which leaves people exposed to influenza infection during superinfection remain unresolved. This paper demonstrates that early infection of monocytes inhibits an arm of immunity crucial to bacterial clearance. Understanding this mechanism may provide alternative interventions in the case of superinfection with antimicrobial resistant strains of bacteria.

We often encounter in distributed systems the need to model, access, and manage state. This state may be, for example, data in a purchase order, service level agreements representing resource availability, or the current load on a computer. We introduce two closely related approaches to modeling and manipulating state within a Web services (WS) framework: the Open Grid Services Infrastructure (OGSI) and WS-Resource Framework (WSRF). Both approaches define conventions on the use of the Web service definition language schema that enable the modeling and management of state. OGSI introduces the idea of a stateful Web service and defines approaches for creating, naming, and managing the lifetime of instances of services; for declaring and inspecting service state data; for asynchronous notification of service state change; for representing and managing collections of service instances; and for common handling of service invocation faults. WSRF refactors and evolves OGSI to exploit new Web services standards, specifically WS-addressing, and to respond to early implementation and application experiences. WSRF retains essentially all of the functional capabilities present in OGSI, while changing some syntax (e.g., to exploit WS-addressing) and also adopting a different terminology in its presentation. In addition, WSRF partitions OGSI functionality into five distinct composable specifications. We explain the relationship between OGSI and WSRF and the related WS-notification specifications, explain the common requirements that both address, and compare and contrast the approaches taken to the realization of those requirements.

Background— Mutations in the γ 2 subunit ( PRKAG2 ) of AMP-activated protein kinase produce an unusual human cardiomyopathy characterized by ventricular hypertrophy and electrophysiological abnormalities: Wolff-Parkinson-White syndrome (WPW) and progressive degenerative conduction system disease. Pathological examinations of affected human hearts reveal vacuoles containing amylopectin, a glycogen-related substance. Methods and Results— To elucidate the mechanism by which PRKAG2 mutations produce hypertrophy with electrophysiological abnormalities, we constructed transgenic mice overexpressing the PRKAG2 cDNA with or without a missense N488I human mutation. Transgenic mutant mice showed elevated AMP-activated protein kinase activity, accumulated large amounts of cardiac glycogen (30-fold above normal), developed dramatic left ventricular hypertrophy, and exhibited ventricular preexcitation and sinus node dysfunction. Electrophysiological testing demonstrated alternative atrioventricular conduction pathways consistent with WPW. Cardiac histopathology revealed that the annulus fibrosis, which normally insulates the ventricles from inappropriate excitation by the atria, was disrupted by glycogen-filled myocytes. These anomalous microscopic atrioventricular connections, rather than morphologically distinct bypass tracts, appeared to provide the anatomic substrate for ventricular preexcitation. Conclusions— Our data establish PRKAG2 mutations as a glycogen storage cardiomyopathy, provide an anatomic explanation for electrophysiological findings, and implicate disruption of the annulus fibrosis by glycogen-engorged myocytes as the cause of preexcitation in Pompe, Danon, and other glycogen storage diseases.

Myotonic dystrophy (DM) is an autosomal dominant multisystem disorder, caused by expansion of a CTG trinucleotide repeat in the 3′ untranslated region of the myotonic dystrophy protein kinase gene (DMPK) on chromosome 19q13. Cardiac involvement in DM includes conduction abnormalities and functional deficits. Three hypotheses of molecular mechanisms for DM pathophysiology are; first, partial loss of myotonic dystrophy protein kinase (DMPK); second, decreased transcription of a neighboring homeodomain-encoding gene, Six5 (or DMAHP), and third, transdominant effects of the RNA and regulation of splicing associated with expression of expanded CUG repeats. However, the precise pathogenetic mechanism remains unresolved. We previously reported that dosage of Dm15, the mouse homologue of DMPK, strongly associates with the cardiac conduction abnormalities. For further distinction of the molecular mechanisms underlying the cardiac phenotype of DM, in the present study, we characterized the cardiac conduction findings of mice with targeted disruption of Six5 gene. Six5 heterozygous mice (adult and young) and their age matched wild type littermates were studied using in vivo electrophysiologic techniques, echocardiography, heart rate variability and exercise tolerance testing. No PR prolongation was detected, however, prolonged QRS duration and delayed infraHisian conduction were significant in adult Six5 heterozygous mice. By echocardiography, left ventricular (LV) end-diastolic dimension was enlarged in adult Six5 heterozygous mice, although neither fractioning shortening nor LV wall thickness showed significant differences. Six5 loss may partly contribute to conduction abnormalities in myotonic dystrophy, particularly infraHisian conduction delay, one of the initial phenotypes of adult-onset cardiac conduction abnormalities in DM patients.

OBJECTIVES We sought to study the role of IKAChin atrial fibrillation (AF) and the potential electrophysiologic effects of a specific IKAChantagonist. BACKGROUND IKAChmediates much of the cardiac responses to vagal stimulation. Vagal stimulation predisposes to AF, but the specific role of IKAChin the generation of AF and the electrophysiologic effects of specific IKAChblockade have not been studied. METHODS Adult wild-type (WT) and IKACh-deficient knockout (KO) mice were studied in the absence and presence of the muscarinic receptor agonist carbachol. The electrophysiologic features of KO mice were compared with those of WT mice to assess the potential effects of a specific IKAChantagonist. RESULTS Atrial fibrillation lasting for a mean of 5.7 ± 11 min was initiated in 10 of 14 WT mice in the presence of carbachol, but not in the absence of carbachol. Atrial arrhythmia could not be induced in KO mice. Ventricular tachyarrhythmia could not be induced in either type of mouse. Sinus node recovery times after carbachol and sinus cycle lengths were shorter and ventricular effective refractory periods were greater in KO mice than in WT mice. There was no significant difference between KO and WT mice in AV node function. CONCLUSIONS Activation of IKAChpredisposed to AF and lack of IKAChprevented AF. It is likely that IKAChplays a crucial role in the generation of AF in mice. Specific IKAChblockers might be useful for the treatment of AF without significant adverse effects on the atrioventricular node or the ventricles.

Genetics are coming to play an increasing role in biomedical understanding of common diseases. The implication of such findings is that at-risk individuals may be offered predictive genetic tests. How do individuals make decisions about predictive tests and what information do they need to make informed choices? Richards [Richards, M.P.M., 1993. The new genetics: some issues for social scientists. Sociology of Health and Illness 15, 567-586] has argued the first step in understanding and helping people to make these decisions is to investigate lay beliefs of genetics. This study examined mental models of inheritance in a sample of 72 lay people. Through analysis of open-ended questionnaires we found three mental models which loosely corresponded to three phases of historical development in the science of genetics. These we labelled the Constitutional, Mendelian and Molecular Models. Predictions for individuals holding each model are made for the comprehension of genetic information in a testing situation.

Introduction: Gap junctions consist of connexin (Cx) proteins that enable electrical coupling of adjacent cells and propagation of action potentials. Cx40 is solely expressed in the atrium and His-Purkinje system. The purpose of this study was to evaluate atrioventricular (AV) conduction in mice with a homozygous deletion of Connexin40 (Cx40−/−). Methods: Surface ECGs, intracardiac electrophysi-ology (EP) studies, and ambulatory telemetry were performed in Cx40−/− mutant mice and wild-type (WT) controls. Atrioventricular (AV) conduction parameters and arrhythmia inducibility were evaluated using programmed stimulation. Analysis of heart rate variability was based on results of ambulatory monitoring. Results: Significant findings included prolonged measures of AV refractoriness and conduction in connexin40-deficient mice, including longer PR, AH, and HV intervals, increased AV refractory periods, and increased AV Wenckebach and 2:1 block cycle lengths. Connexin40-deficient mice also had an increased incidence of inducible ventricular tachycardia, decreased basal heart rates, and increased heart rate variability. Conclusion: A homozygous disruption of Cx40 results in prolonged AV conduction parameters due to abnormal electrical coupling in the specialized conduction system, which may also predispose to arrhythmia vulnerability.

Introduction: Myotonic dystrophy is caused by expansion of a CTG trinucleotide repeat on human chromosome 19, and leads to progressive skeletal myopathy and atrioventricular conduction disturbances. A murine model of myotonic dystrophy has been designed by targeted disruption of the myotonic dystrophy protein kinase (DMPK) gene. The DMPK-deficient mice display abnormalities in A-V conduction characteristics, similar to the human cardiac phenotype. The purpose of this study was to determine whether age-related progression of A-V block occurs in a mouse model of DMPK-deficiency.

Objectives. No standard noninvasive diagnostic test reliably differentiates patients with organ-confined prostate cancer from those with lymph node metastases. The ability of a radiolabeled monoclonal antibody, indium-111 ( 111 In)-capromab pendetide, to identify sites of metastatic disease in patients at moderate to high risk of nodal involvement was investigated. Methods. The study prospectively evaluated 160 patients with prostate cancer scheduled to undergo pelvic lymph node dissection (PLND) before or during definitive treatment. All were at relatively high risk of nodal involvement by virtue of significantly elevated baseline prostate-specific antigen (PSA) values, Gleason scores, and/or locally advanced clinical stages of disease. The histologic findings of the PLNDs were compared with the results of immunoscintigraphy, computed tomography, and magnetic resonance imaging. Results. Among the 152 evaluable patients studied with 111 In-capromab pendetide before PLND, the sensitivity of immunoscintigraphy for lymph node detection was 62% and the specificity was 72%; the positive predictive value was 62% and the negative predictive value was 72%. In comparison, the sensitivity of computed tomography and magnetic resonance imaging was 4% and 15%, respectively, and the specificity was 100% for both procedures on the basis of a large number of negative interpretations. Logistic regression analysis revealed that immunoscintigraphy with 111 In-capromab pendetide provided strong, independent evidence of the presence of lymph node metastases. Furthermore, the analysis indicated that certain combinations of PSA, Gleason score, and 111 In-capromab pendetide were particularly effective at predicting the risk of nodal involvement. Conclusions. Immunoscintigraphy with 111 In-capromab pendetide outperformed standard diagnostic imaging techniques in the detection of prostate cancer lymph node metastases and provided independent prognostic information that complemented PSA, Gleason score, and clinical stage.

Urokinase plasminogen activator (uPA) is a serine protease causally involved in cancer invasion and metastasis. Consistent with its role in cancer spread, uPA has been shown to be a prognostic marker in a variety of malignancies, especially breast cancer. Approximately 20 different groups have shown that high levels of uPA in breast tumor tissue predict poor outcome. As a prognostic marker in breast cancer, uPA provides information that is independent of traditionally used factors such as tumor size, tumor grade, axillary node status and estrogen receptor status. Furthermore, uPA is prognostic in node-negative patients, and a clinical trial is currently under way to assess whether uPA and its inhibitor, plasminogen activator inhibitor-1, can differentiate between the majority of node-negative breast cancer patients who are cured by surgery from the minority who might benefit from adjuvant therapy. uPA is also prognostic in other malignancies, such as gastric, colorectal, esophageal, renal, endometrial, and ovarian cancers. uPA may thus be a prognostic indicator for multiple types of adenocarcinoma.

Patients with familial hypertrophic cardiomyopathy (FHC) are at risk for ventricular arrhythmias and sudden death. Regional variability in the QT interval [QT dispersion (QTd)] is significantly increased in humans with FHC and ventricular arrhythmias. A mouse model of FHC resulting from a mutation in the alpha-myosin heavy-chain (Arg403Gln) was used to study the electrophysiologic phenotype of this disease. Cardiac electrophysiology studies and surface ECGs were performed in FHC mice and wild-type controls to evaluate the feasibility and significance of QTd measurements in predicting the risk for ventricular arrhythmias. Atrial and ventricular pacing electrodes were placed by either a transvenous or epicardial approach. Standard pacing and extrastimulus protocols were followed. The QT interval was measured in six surface ECG leads. QTd was defined as the difference between the maximum and minimum measured QT intervals. Male FHC mice had greater QTd than wild-type controls (37.1 +/- 3.0 ms versus 23.9 +/- 1.9 ms, p = 0.001). There was also a significant gender difference in QTd within each genotype; female wild-type mice had greater QTd than male wild-type mice (37.4 +/- 5.3 ms versus 23.9 +/- 1.9 ms, p = 0.005), and male FHC mice had greater QTd than female FHC mice (37.1 +/- 3.0 ms versus 27.2 +/- 2.0 ms, p = 0.02). Twelve of 23 FHC mice had inducible ventricular arrhythmias, whereas only 2 of 32 wild-type mice were inducible (p = 0.004). Although a significantly increased number of FHC mice had arrhythmias compared with wild-type mice, QTd did not correlate with arrhythmia inducibility. The importance of this study is that it validates the mouse model for further investigation of arrhythmogenic risk and gender differences in the electrophysiologic phenotype in FHC. It also suggests that although gender- and genotype-specific QTd values are increased, they do not predict arrhythmia risk in FHC mice.

BACKGROUND The pretherapy prediction of occult lymph node involvement and the avoidance of otherwise futile and potentially morbid definitive local therapy is paramount in men with newly diagnosed prostate carcinoma. To identify patients with prostate carcinoma who likely have lymph node involvement and would benefit from staging lymphadenectomy prior to definitive local therapy, the authors compared the ability of several predictive staging algorithms and a radiolabeled monoclonal antibody scan to predict lymphatic metastases prior to treatment. METHODS Between August 1991 and June 1994, 198 men with clinical T2 or T3 classified (TNM) prostate carcinoma (bone scan negative) who were at high risk of lymph node involvement underwent a 111In-capromab pendetide scan prior to staging lymphadenectomy. Several predictive models based on preoperative prostate specific antigen level, biopsy Gleason score, and clinical stage were selected to predict those men having a ≥20% probability of lymph node involvement. The ability to predict pathologic stage using several clinical algorithms and the monoclonal antibody scan was compared with pathologic examination of the lymph nodes. RESULTS Overall, 39% of the pelvic lymph node specimens were positive for metastatic disease by pathologic analysis. Published algorithms predicting lymph node metastases had a positive predictive value (PPV) ranging from 40.5% to 46.6% and an area under the receiver operating characteristic curve (AUC) ranging from 0.52 to 0.61. The monoclonal antibody scan had a PPV of 66.7% and an AUC of 0.71. The differences between the PPV and the AUC for the individual clinical algorithms when compared with immunoscintigraphy were statistically significant. Combining the radiolabeled monoclonal antibody scan with clinical predictive models, a PPV of up to 72.1% could be obtained. CONCLUSIONS These data suggest that the PPVs for the clinical predictive algorithms are similar and that the PPV of the radiolabeled monoclonal antibody scan alone or in combination with the algorithms has additional value in predicting lymph node involvement in prostate carcinoma patients at high risk of regional disease spread. These algorithms and the 111In-capromab pendetide scan may be used for the appropriate selection of candidates for definitive local therapy in men with clinically localized prostate carcinoma and significant risk of lymph node involvement. Cancer 1999;85:1586–92. © 1999 American Cancer Society.

There is currently no curative therapy for men who have disseminated prostate cancer following failed radical prostatectomy. The purpose of this trial was to investigate systemic radioimmunotherapy in these men. Eight patients with occult metastatic prostate cancer following radical prostatectomy as evidenced solely by a rising serum PSA and evidence of soft tissue lesions outside the prostatic fossa detected by an [111I]indiumcapromab pendetide scan received an infusion of 10 mg of capromab pendetide labeled with 9 mCi/m2 of [90Y]yttrium. Serum PSA was used to measure response rate. There were no complete or partial responses by PSA criteria. Significant unexpected bone marrow toxicity developed in the first 6 of 8 patients treated. The last two patients received co-infusion of edetate calcium disodium in an effort to decrease marrow suppression. In these two patients less marrow toxicity was seen. Repeat 111In-capromab pendetide scans were uninterpretable due to grossly altered whole-body biodistribution of the radioimmunoconjugate. Retrospective analysis of serial PSA values after closure of the study showed a decrease in the log slope PSA for seven of eight patients following radioimmunotherapy, with a statistically significant change in the mean log slope (p = 0.01). The clinical significance of this small but measurable change is uncertain. We conclude that radioimmunotherapy for occult metastatic prostate cancer using 90Y-capromab-pendetide at the dose described does not lower serum PSA, is associated with significant hematologic toxicity, and leads to complexation of the immunoconjugate following subsequent capromab pendetide infusion.

Analysis for an avionics application typical of remotely located, intermittently operated avionics on aircraft and missiles show that a large weight reduction (about 9:1) can be obtained by using recently developed microencapsulated phase change materials technology instead of a solid aluminum plate for a passive heat sink. Tests with a configuration based on the typical avionics application used for analysis show good agreement with analysis. Use of microencapsulated rather than bulk phase change materials avoids a number of design problems previously encountered with application of such materials.

Purpose: Standard diagnostic methods are limited for detecting distant metastases in patients with prostate cancer in whom the only evidence of disease after radical prostatectomy is a detectable prostate specific antigen (PSA) level. We evaluated the role of immunoscintigraphy with the radiolabeled monoclonal antibody,111 indium (111) In)-capromab pendetide, to differentiate between local and distant recurrence in this patient population.Materials and Methods: We enrolled 183 men who had undergone radical prostatectomy in whom PSA later increased. Gamma camera images were acquired twice after infusion of a single dose of111 In-capromab pendetide.Results: Immunoscintigraphy revealed disease in 108 of 181 patients (60%) with interpretable scans. The antibody was localized most frequently to the prostatic fossa (34% of the cases), abdominal lymph nodes (23%) and pelvic lymph nodes (22%). Of the 181 men the scan localized the antibody outside the prostatic fossa in 42%. Half of the positive localizat...

As research in human genetics advances, genes for familial forms of cancer and heart disease will continue to be identified. The implication of such findings is that at-risk individuals will be offered a predictive genetic test. How do individuals make such decisions and what information do they need to make informed choices? Richards (1993) has argued that the first step in understanding and helping people to make these decisions is to investigate lay beliefs of genetics. This study examined illness representations of genetic disease, and predictive testing in a sample of 20 educated lay people. Through content analysis of open-ended interviews, we discovered that individuals have limited knowledge of late-onset genetic disorders and predictive testing. Most of the sample identified genetic diseases that manifest in childhood, and were more familiar with prenatal testing. They did not mention any treatment options for genetic disorders, which may indicate that lay people are more deterministic about diseases with a genetic component. Finally, they consistently raised concerns about the ethics of genetic testing and research. The implications of our findings for the provision of information in a genetic testing situation are discussed.

BACKGROUND Stored serum from clinical trial cases undergoing ProstaScint® (CYT-356) scanning were available for Prostate Specific Membrane Antigen (PSMA) assay. Prostate Specific Antigen (PSA) levels had already been determined. This provided an opportunity to see what correlations existed between the serum markers and the ProstaScint® scan. A group of patients had the studies preprostatectomy, whereas another group had the studies postprostatectomy. METHODS The scan results, serum PSA, serum PSMA, and clinical data were separately analyzed. PSMA serum levels were determined by Western blot. RESULTS Preoperatively, radical prostatectomy patients showed a correlation between serum PSA or PSMA levels and the ProstaScint® scan in the total group (n = 86), or in an untreated group (n = 38). Preoperatively, PSMA correlated with the pathological stage, whereas PSA correlated with the scan. Postoperatively, only PSMA serum levels correlated with the scan in an untreated group (n = 40). CONCLUSIONS Preoperatively or postoperatively, Western blot PSMA serum levels predict the stage of disease or local, regional, or distant metastases, as shown by ProstaScint® scan. Both the scan and the serum tests provide prognostic information and evaluate the extent of disease to a more significant degree than previously possible. Prostate 33:281–285, 1997. © 1997 Wiley-Liss, Inc.

Genetically-manipulated mice harboring an α-myosin heavy chain Arg403Gln missense mutation (α-MHC 403/+ ) display a phenotype characteristic of familial hypertrophic cardiomyopathy (FHC). Male and female (30±8 week old) heterozygous α-MHC 403/+ mice and littermate controls were evaluated using a surface electrocardiogram (ECG) and an in vivo cardiac electrophysiology study (EPS). Wild type animals had normal intracardiac electrophysiology, with no significant differences between male and female control mice during EPS. The female wild-type mice did have slower heart rates and longer ECG intervals than their male wild-type counterparts. The female α-MHC 403/+ mice had similar ECG's, cardiac conduction times, and refractory periods compared with female wild-type mice. In contrast, male FHC mice had distinctive ECG and electrophysiologic abnormalities including right axis deviation, prolonged ventricular repolarization and prolonged sinus node recovery times. During programmed ventricular stimulation, 62% of male α-MHC 403/+ mice and 28% of female α-MHC 403/+ mice had inducible ventricular tachycardia. These studies identify gender-specific electrophysiologic abnormalities in α-MHC 403/+ FHC mice, concordant with the histological and hemodynamic derangements previously reported.

PURPOSE: The role of immunoscintigraphy with111 Insatumomab pendetide in the medical and/or surgical management of colorectal cancer patients was evaluated in a multicenter trial. METHODS: This 103 patient study population included 46 individuals with rising serum carcinoembryonic antigen levels and otherwise negative diagnostic evaluation, 29 patients with known recurrence, presumed to be isolated and resectable, and 28 patients for whom standard diagnostic tests provided equivocal information. RESULTS: No adverse reactions were noted following intravenous administration of 1 mg of satumomab pendetide radiolabeled with approximately 5 mCi of111 In. Thirty percent of patients developed human anti-mouse antibodies postinfusion. In the 84 patients for whom correlation with histopathologic, diagnostic, and/or clinical findings was available, antibody imaging demonstrated a sensitivity of 73 percent in patients with confirmed tumor (36/49) and negative results for all 35 patients with no evidence of malignancy. Occult disease was detected in 18 patients. CONCLUSION: 111 In-satumomab pendetide immunoscintigraphy was helpful in the medical and/or surgical management of 45 (44 percent) patients and provided information unavailable from other diagnostic modalities.

Most tumor markers in routine clinical practice lack organ specificity (1). For example, CA 15-3, BR 27.29, and carcinoembryonic antigen, which are widely used serum markers for breast cancer, can be increased in patients with most types of adenocarcinoma, especially if distant metastases are present [for a review, see Ref. (2)]. Using a modified differential display technique, Watson and Fleming (3)(4) identified a novel gene that appeared to be expressed only in breast tissue. This gene, which was designated mammaglobin ( MG ), was found to encode a 93-amino acid protein with a predicted molecular mass of 10.5 kDa (4). MG mRNA expression was reported to be increased at least 10-fold relative to nonmalignant breast tissue in 8 of 35 (23%) breast carcinomas (4), and MG protein was detected by immunohistochemistry in 81 of 100 breast cancers (5). MG was detected by quantitative reverse transcription-PCR in 31 of 42 (74%) primary breast cancers (6) and was either undetectable or present at low concentrations in small numbers of nonbreast tissues (4)(5)(6). In 1998, Becker et al. (7) identified a new gene with marked sequence identities to MG . This new gene was named mammaglobin B ( MGB ) (7), and the original MG was redesignated mammaglobin A ( MGA ). Both MGA and MGB and several related genes [e.g., Clara cell 10-kDa protein, lipophilin A, and lipophilin B ( LPB )] are localized in a dense cluster on chromosome 11q12.2 …

Application of monoclonal antibody (MoAb) technology to cancer management is discussed by reviewing the development and clinical evaluation of two MoAb-based immunoscintigraphic agents (111In-satumomab pendetide [OncoScint CR/OV-In] and 111In-CYT-356; Cytogen Corporation, Princeton, NJ). Both agents were prepared using a site-specific MoAb modification method that preserves the immunoreactivity of the radiolabeled immunoconjugate. 111In-satumomab pendetide is an 111In-labeled conjugate of the murine MoAb B72.3, which is directed to TAG-72, an antigen expressed by the majority of adenocarcinomas. By providing information that complements the results of standard radiographic diagnostic modalities, this imaging agent can aid in the treatment of patients with colorectal or ovarian cancer. Immunoscintigraphy with 111In-satumomab pendetide has been shown to assist in medical-surgical management by detecting occult extrahepatic lesions, clarifying equivocal results of other diagnostic imaging tests, and evaluating the extent and resectability of known tumor lesions. 111In-CYT-356 is an 111In-labeled conjugate of the murine MoAb 7E11-C5.3, which is reactive with prostatic carcinoma, benign prostatic hypertrophy, and, to a lesser extent, normal prostatic tissue. Results of preliminary clinical investigations suggest that 111In-CYT-356 immunoscintigraphy can be useful for the presurgical staging of prostatic carcinoma and for the detection of occult distant disease in patients with negative or equivocal results on standard imaging tests. Results with these site-specifically radiolabeled immunconjugates demonstrate the clinical utility of MoAb-based imaging agents in the treatment of patients with solid tumors.

This review of the literature has summarized two challenges presented to physicians as we move into the second decade of the AIDS epidemic: 1) the low proportions of physicians playing their role in assessing patients’ sexual risk for HIV infection and providing relevant risk reduction counseling and education, and 2) the reluctance of physicians to provide care to those with HIV disease due to homophobia, IVDU aversion, and fear of contagion. In view of the growing number of HIV-infected patients and patients living with AIDS, physicians and medical educators alike must confront these challenges.

Because many dentists were trained before HIV disease was recognized and its implications for dentistry understood, there is a need for effective continuing education programs about the disease for health professionals. Unfortunately, much of the continuing professional education about AIDS in the last few years has been poorly evaluated and the value of continuing education itself has increasingly been called into question. In order to clarify how continuing educational efforts can be designed and evaluated, we report on our continuing educational projects and research which culminated in research on a nationwide educational intervention about AIDS for dentists. We outline and evaluate the steps taken in designing both the intervention and the research. The strengths and weaknesses of the design are discussed and suggestions made about how the design could be improved.

This chapter summarizes experimental techniques used to study coronary vessel development from its origins in the proepicardium (PE) to the final assembled network of arteries, veins, and capillaries present in the mature heart. Methods are described for microdissection and culture of the PE and embryonic epicardial cells, isolation of total RNA from single PE primordia and analysis by RT‐PCR, imaging of the epicardium and coronary vessels by whole‐mount confocal microscopy and by scanning electron microscopy, and the preparation of coronary vascular corrosion casts to visualize the entire coronary artery network structure. These techniques form the basic tools to study the cellular and molecular pathways that guide development and remodeling of coronary vessels.

Recordable CD and DVD discs enable custom content, creating the demand for custom labeling. LightScribe Direct Disc Labeling leverages optical recording technology to create labels with the same drive used to record the data.

Today's power system environment is becoming more and more complex. Electrical power networks are being pushed closer to their limits, while at the same time higher reliability and efficiency are demanded. As a result, electrical equipment manufacturers are developing advanced equipment and installations to meet these requirements. Part of the challenge in designing such apparatus is the need to accurately simulate (prove) and test these devices before they are installed in an actual power system. The real time digital simulator (RTDS) allows developers to accurately and efficiently simulate electrical power systems and their ideas to improve them. The RTDS simulator operates in real time, therefore not only allowing the simulation of the power system, but also making it possible to test physical protection and control equipment. This gives developers the means to prove their ideas, prototypes and final products in a realistic environment. This paper will summarize the fundamental design of the RTDS simulator, with particular emphasis on recent developments and enhancements. It will also describe practical applications of the simulator in the various stages of power system design, testing and implementation. A brief description of ongoing development for the real time simulation of voltage source converter (VSC) converters is included.

ObjectivesWe sought to characterize an animal model of the Wolff-Parkinson-White (WPW) syndrome to help elucidate the mechanisms of accessory pathway formation.BackgroundPatients with mutations in PRKAG2manifest cardiac hypertrophy and ventricular pre-excitation; however, the mechanisms underlying the development and conduction of accessory pathways remain unknown.MethodsWe created transgenic mice overexpressing either the Asn488Ile mutant (TGN488I) or wild-type (TGWT) human PRKAG2complementary deoxyribonucleic acid under a cardiac-specific promoter. Both groups of transgenic mice underwent intracardiac electrophysiologic, electrocardiographic (ECG), and histologic analyses.ResultsOn the ECG, ∼50% of TGN488Imice displayed sinus bradycardia and features suggestive of pre-excitation, not seen in TGWTmice. The electrophysiologic studies revealed a distinct atrioventricular (AV) connection apart from the AV node, using programmed stimulation. In TGN488Imice with pre-excitation, procainamide blocked bypass tract conduction, whereas adenosine infusion caused AV block in TGWTmice but not TGN488Imice with pre-excitation. Serial ECGs in 16 mice pups revealed no differences at birth. After one week, two of eight TGN488Ipups had ECG features of pre-excitation, increasing to seven of eight pups by week 4. By nine weeks, one TGN488Imouse with WPW syndrome lost this phenotype, whereas TGWTpups never developed pre-excitation. Histologic investigation revealed postnatal development of myocardial connections through the annulus fibrosum of the AV valves in young TGN488Ibut not TGWTmice.ConclusionsTransgenic mice overexpressing the Asn488Ile PRKAG2mutation recapitulate an electrophysiologic phenotype similar to humans with this mutation. This includes procainamide-sensitive, adenosine-resistant accessory pathways induced in postnatal life that may rarely disappear later in life.

342 Background: Rigosertib (ON 01910.Na), a dual non-ATP inhibitor of polo-like kinase 1 (Plk1) and phosphoinositide 3-kinase (PI3K) pathways, was assessed in patients with treatment-naïve metastatic pancreatic adenocarcinoma. Methods: Patients with metastatic adenocarcinoma of the pancreas were randomized in a 2:1 fashion to gemcitabine 1000 mg/m2 weekly for 3 weeks of a 4-week cycle plus rigosertib 1800mg/m2 via 2-hr CIV infusions given twice weekly for 3 weeks of a 4-week cycle versus gemcitabine 1000mg/m2 weekly for 3 weeks in a 4-week cycle. Results: A total of 160 patients were enrolled globally and randomly assigned to rigosertib plus gemcitabine (106 patients) or gemcitabine (54). The most common grade 3 or higher adverse events were neutropenia (8% in the rigosertib plus gemcitabine group vs. 6% in the gemcitabine group), hyponatremia (17% vs. 4%), and anemia (8% vs. 4%). The primary outcome of the study, median OS, was 6.1 months in the gemcitabine plus rigosertib arm versus 6.4 months with gemcitabine alone (hazard ratio (HR), 1.24; 95% confidence interval [CI], 0.85-1.81). The median PFS was 3.4 months for both groups (HR, 0.96; 95% CI, 0.68-1.36). The overall best response between arms were partial response rates of 19% versus 13% and stable disease in 50% versus 56% in the gemcitabine plus rigosertib versus gemcitabine alone, respectively. Of 64 tumor samples sent for molecular analysis, 47 were adequate for multiplex genetic testing and 41 were positive for mutations. The majority of cases had KRAS gene mutations (40/47, 85%), which included c.35G>T, p.G12V (12 cases), c.35G>A, p.G12D (21 cases), c.34G>C, p.G12R (4 cases), c.34G>T, p.G12C (1 case) and c.183C>A, p.Q61H (2 cases). Other mutations detected included TP53 (13 cases) and PIK3CA(1 case). No correlation between mutational status and efficacy was detected. Conclusions: The combination of rigosertib plus gemcitabine failed to demonstrate an improvement in survival or response compared to gemcitabine alone in metastatic pancreatic adenocarcinoma. Clinical trial information: NCT01360853.

This paper presents details of the design and applications of a real-time digital simulator, RTDS/sup TM/, applied to the modelling of power system transients. This paper outlines the hardware and software design aspects of the RTDS. The hardware architecture is based on parallel processing techniques and employs many high-speed digital signal processors. Sophisticated graphical interface software facilitates circuit assembly and simulator operation. Detailed power system component models together with flexible analogue and digital I/O enable detailed testing of power systems and external devices connected to such systems. The RTDS can be applied in various areas of power system study. Specific applications which have been identified include closed-loop protective relay testing, control equipment testing, analogue simulator expansion and operation as a power system training tool.

Abstruct - This paper presents details on the design, architectural features and applications of a real-time digital simulator (RTDSm) developed at the Manitoba HVDC Research Centre (Winnipeg, Canada). Custom hardware and software have been developed and collectively applied to the simulation and study of electromagnetic transients phenomenon in power systems in real-time. The combination of real-time operation, flexible YO, graphical user interface and an extensive library of accurate power system component models make the RTDS an ideal simulation tool with a wide range of applications. I. INTRODUCTION Simulation has long been recognized as an important and necessary step in the development, design and testing of power generation and transmission systems. A wide variety of both analogue and digital simulation tools are available and typically used during various stages of system development. Recent advances in both computing hardware and sophisticated power system component modelling techniques have significantly increased the application of digital simulation in the power system industry. Of particular interest in the context of this paper are the advances made in the study of electromagnetic transients phenomenon.

Acetylcholine released on parasympathetic stimulation slows heart rate through activation of muscarinic receptors on the sinus nodal cells and subsequent opening of the atrial muscarinic potassium channel (KACh). KAChis directly activated by G protein βγ-subunits. To elucidate the physiological role of Gβγ for the regulation of heart rate and electrophysiological function in vivo, we created transgenic mice with a reduced amount of membrane-bound Gβ protein by overexpressing nonprenylated Gγ2-subunits in their hearts using the α-myosin heavy chain promoter. At baseline and after muscarinic stimulation with carbachol, heart rate and heart rate variability were determined with electrocardiogram telemetry in conscious mice and in vivo intracardiac electrophysiological studies in anesthetized mice. Reduction of the amount of functional Gβγ protein by >50% caused a pronounced blunting of the carbachol-induced bradycardia as well as the increases in time- and frequency-domain indexes of heart rate variability and baroreflex sensitivity that were observed in wild types. In addition, sinus node recovery time and inducibility of atrial arrhythmias were reduced in transgenic mice. Our data demonstrate in vivo that Gβγ plays a crucial role for parasympathetic heart rate control, sinus node automaticity, and atrial arrhythmia vulnerability.

Background Genetically altered mice will provide important insights into a wide variety of processes in cardiovascular physiology underlying myocardial infarction (MI). Comprehensive and accurate analyses of cardiac function in murine models require implementation of the most appropriate techniques and experimental protocols. Objective In this study we present in vivo, whole-animal techniques and experimental protocols for detailed electrophysiological characterization in a mouse model of myocardial ischemia and infarction. Methods FVB mice underwent open-chest surgery for ligation of the left anterior descending coronary artery or sham-operation. By means of echocardiographic imaging, electrocardiography, intracardiac electrophysiology study, and conscious telemetric ECG recording for heart rate variability (HRV) analysis, we evaluated ischemic and post-infarct cardiovascular morphology and function in mice. Results Coronary artery ligation resulted in antero-apical infarction of the left ventricular wall. MI mice showed decreased cardiac function by echocardiography, infarct-typical pattern on ECG, and increased arrhythmia vulnerability during electrophysiological study. Electrophysiological properties were determined comprehensively, but were not altered significantly as a consequence of MI. Autonomic nervous system function, measured by indices of HRV, did not appear altered in mice during ischemia or infarction. Conclusions Cardiac conduction, refractoriness, and heart rate variability appear to remain preserved in a murine model of myocardial ischemia and infarction. Myocardial infarction may increase vulnerability to inducible ventricular tachycardia and atrial fibrillation, similarly to EPS findings in humans. These data may be of value as a reference for comparison with mutant murine models necessitating ischemia or scar to elicit an identifiable phenotype. The limitations of directly extrapolating murine cardiac electrophysiology data to conditions in humans need to be considered.

Background: Atrial tachycardia and fibrillation in humans may be partly consequent to vagal stimulation. Induction of fibrillation in the small heart is considered to be impossible due to lack of a critical mass of >100–200 mm2. Even with the recent progression of the technology of in vivo and in vitro mouse electrophysiological studies, few reports describe atrial tachycardia or fibrillation in mice. The purpose of this study was to attempt provocation of atrial tachyarrhythmia in mice using transvenous pacing following cholinergic stimulation. Methods and results: In vivo electrophysiology studies were performed in 14 normal mice. A six-lead ECG was recorded from surface limb leads, and an octapolar electrode catheter was inserted via jugular vein cutdown approach for simultaneous atrial and ventricular endocardial recording and pacing. Atrial tachycardia and fibrillation were inducible in one mouse at baseline electrophysiology study and eleven of fourteen mice after carbamyl choline injection. The mean duration of atrial tachycardia was 126±384 s. The longest episode lasted 35 min and only terminated after atropine injection. Reinduction of atrial tachycardia after administration of atropine was not possible. Conclusion: Despite the small mass of the normal mouse atria, sustained atrial tachycardia and fibrillation can be easily and reproducibly inducible with endocardial pacing after cholinergic agonist administration. This finding may contribute to our understanding of the classical theories of arrhythmogenesis and critical substrates necessary for sustaining microreentrant circuits. The techniques of transcatheter parasympathetic agonist-mediated atrial tachycardia induction may be valuable in further murine electrophysiological studies, especially mutant models with potential atrial arrhythmia phenotypes.

The new 400 kV interconnection between Namibia and South Africa was successfully commissioned in the last quarter of 2000. The 890 km single circuit 400 kV AC transmission line interconnects the two systems, ESKOM and NamPower, at the Aries substation near Kenhardt in South Africa and the Auas substation near Windhoek in Namibia. With the new interconnection, the NamPower system is strengthened, but the new 400 kV line is also very long with a large charging capacitance which aggravates the inherent problems in the NamPower system; namely voltage stability and near 50 Hz resonance. The charging capacitance shifts the existing parallel resonance very close to 50 Hz and makes the network more voltage sensitive during system transients such as 400 kV line energisation or recovery after clearing of line faults. The authors describe how the SVC performance of this system has been verified by RTDS and field tests.

Mouse AV Nodal Maturation. Introduction: Dual AV nodal physiology is characterized by discontinuous conduction from the atrium to His bundle during programmed atrial extrastimulus testing (A2V2 conduction curves), AV nodal echo beats, and induction of AV nodal reentry tachycardia (AVNRT). The purpose of this study was to characterize in vivo murine maturational AV nodal conduction properties and determine the frequency of dual AV nodal physiology and inducible AVNRT. Methods and Results: A complete transvenous in vivo electrophysiologic study was performed on 30 immature and 19 mature mice. Assessment of AV nodal conduction included (1) surface ECG and intracardiac atrial and ventricular electrograms; (2) decremental atrial pacing to the point of Wenckebach block and 2:1 conduction; and (3) programmed premature atrial extrastimuli to determine AV effective refractory periods (AVERP), construct A2V2 conduction curves, and attempt arrhythmia induction. The mean Wenckebach block interval was 73 ± 12 msec, 2:1 block pacing cycle length was 61 ± 11 msec, and mean AVERP100 was 54 ± 11 msec. The frequency of dual AV nodal physiology increased with chronologic age, with discontinuous A2V2, conduction curves or AV nodal echo heats in 27% of young mice < 8 weeks and 58% in adult mice (P = 0.03). Conclusion: These data suggest that mice, similar to humans, have maturation of AV nodal physiology, hut they do not have inducible AVNRT. Characterization of murine electrophysiology may be of value in studying genetically modified animals with AV conduction abnormalities. Furthermore, extrapolation to humans may help explain the relative rarity of AVNRT in the younger pediatric population.

This paper outlines the hardware and software design aspects of a real-time digital simulator (RTDS). The hardware architecture is based on parallel processing techniques and employs many high-speed digital signal processors. Sophisticated graphical interface software facilitates circuit assembly and simulator operation. Detailed power system component models together with flexible analogue and digital I/O enable detailed testing of power systems and external devices connected to such systems. The RTDS can be applied in various areas of power system study. Specific applications which have been identified include closed-loop protective relay testing, control equipment testing, analogue simulator expansion and operation as a power system training tool.

Urokinase plasminogen activator (uPA) is a serine protease involved in cancer invasion and metastasis. uPA mediates its action while attached to a membrane-bound receptor (uPAR). In this investigation we show that uPAR levels correlate with uPA levels in human breast cancers. uPAR levels, however, do not correlate with other components of the plasminogen activator system such as tissue-type plasminogen activator (t-PA), PAI-1 or PAI-2. In addition, uPAR levels showed no correlation with tumor size, axillary-node status or estrogen-receptor status. On the basis of an optimum cut-off point, patients with breast cancers containing high levels of uPAR had a worse prognosis than patients with low levels of the receptor. However, as a prognostic marker in breast cancer, uPAR was not as strong as uPA. Our results are consistent with data from model systems suggesting that both uPA and uPAR are necessary for metastasis. © 1995 Wiley-Liss, Inc.

A phase I study was designed to evaluate the safety and pharmacokinetics of a novel platelet reactive peptide, peptide acetyl-SYGRGDVRGDFKCTCCA-amide (CYT-379), which binds to the fibrinogen receptor of activated platelets and also binds to 99m Tc. Eleven subjects with suspected deep venous thrombosis had 0.1, 0.5 or 1.0 mg of the peptide infused intravenously. Pharmacokinetics were determined by assaying blood samples in 6 of the 11 subjects and by urine sampling in 5 of these 6 subjects. Plasma and whole blood time-activity curves demonstrated an initial fast component with half-time clearance of 0.2 ± 0.01 and 0.2 ± 0.02 h and a slow component with half-time clearance of 2.8 ± 0.3 and 2.7 ± 0.2 h (mean ± SEM for plasma and whole blood, respectively). Urine clearance was 22.6 ± 3.3 and 10.8 ± 1.6 mL/min when normalized to body surface area. The cumulative excretion of 99m Tc-CYT-379 in the urine was 16.6 ± 3.6, 45.6 ± 16.9 and 45.6 ± 1.8% of the administered dose over 0–2, 0–12 and 0–24 h after radiopharmaceutical injection, respectively. Images obtained in 11 subjects immediately, at 1–2, and 4–6 h after injection were evaluated for abnormalities and were compared with duplex Doppler ultrasonography. 99m Tc-CYT-379 images were positive in only 3 of 7 subjects who had a positive duplex Doppler examination in at least one lower extremity. One subject with negative duplex Doppler had also negative 99m Tc-CYT-379 scintigraphy. One subject with negative scintigraphy and two other subjects with positive scintigraphy had no other imaging studies of the deep venous system performed. No adverse reactions were observed during or after the infusion of 99m Tc-CYT-379. 99m Tc-CYT-379 appears to be a safe radiopharmaceutical and demonstrates rapid clearance from plasma in human subjects.

We conducted a survey of a random sample of California orthodontists and of general dentists to compare their infection control procedures. Questionnaires were returned by 124 orthodontists (56% response rate) and 126 general dentists (61% response rate). Eighteen questions were asked covering practice profile, perception of risk from hepatitis B virus (HBV) and human immunodeficiency virus (HIV), exposure to blood, barrier protection used, and sterilization and disinfection procedures. Gloves always were worn by 80% of the orthodontists sampled, 63% always wore glasses, and 59% changed gloves between patients. Orthodontists sterilized their instruments 66% of the time and pliers 49% of the time. Compared with general dentists, orthodontists' perception of risk, use of barrier protection, and sterilization and disinfection procedures were lower in all areas. Our data suggest that poorer performance may be because orthodontists: (1) perceive their younger population of patients at less risk for HBV and HIV; (2) treat 2.5 times as many patients, which increases the costs of infection control; (3) do not use invasive procedures; and (4) perceive that glove use decreases dexterity. Orthodontists should follow the American Dental Association/Council on Dental Therapeutics infection control guidelines for universal precautions. To meet these guidelines, orthodontists still need improvement in all aspects of their infection control procedures.

The estrogen receptor (ER) is the most useful marker currently available for breast cancer, being used both to predict response to therapy and assess prognosis. Recently, a new form of the ER, known as ER-beta, was identified. In this preliminary study we show that ER-beta mRNA was expressed less frequently in breast cancers than ER-alpha. ER-alpha but not ER-beta levels correlated with ER protein as determined by ELISA. We conclude that ER-beta is expressed in approximately 50% of breast cancers but it does not appear to be detected by a widely available ELISA.