Effects of SP500263, a novel, potent antiestrogen, on breast cancer cells and in xenograft models.

We have compared the antitumor activities of SP500263, a novel next-generation selective estrogen receptor modulator (SERM), tamoxifen, and raloxifene side-by-side in in vitro and in vivo MCF-7 breast cancer models. In vitro, SP500263 acted as an antiestrogen and potently inhibited estrogen-dependent MCF-7 proliferation with IC(50) values in the nanomolar range. SP500263 also strongly inhibited MCF-7 proliferation in the absence of estrogen at all of the concentrations tested.

SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase.

Jun N-terminal kinase (JNK) is a stress-activated protein kinase that can be induced by inflammatory cytokines, bacterial endotoxin, osmotic shock, UV radiation, and hypoxia. We report the identification of an anthrapyrazolone series with significant inhibition of JNK1, -2, and -3 (K(i) = 0.19 microM).

Real-time assessment of myocardial perfusion and wall motion during bicycle and treadmill exercise echocardiography: comparison with single photon emission computed tomography.

Objectives: We sought to determine the feasibility and accuracy of real-time imaging of myocardial contrast echocardiography (MCE) in detecting myocardial perfusion defects during exercise echocardiography compared with radionuclide tomography.

Background: Ultrasound imaging at a low mechanical index and frame rate (10 to 20 Hz) after intravenous injections of perfluorocarbon containing microbubbles has the potential to evaluate myocardial perfusion and wall motion (WVM) simultaneously and in real time.

Methods: One hundred consecutive patients with intermediate-to-high probability of coronary artery disease underwent treadmill (n = 50) or supine bicycle (n = 50) exercise echocardiography.

PLIP, a novel splice variant of Tip60, interacts with group IV cytosolic phospholipase A(2), induces apoptosis, and potentiates prostaglandin production.

The group IV cytosolic phospholipase A(2) (cPLA(2)) has been localized to the nucleus (M. R. Sierra-Honigmann, J.

TRIP-Br: a novel family of PHD zinc finger- and bromodomain-interacting proteins that regulate the transcriptional activity of E2F-1/DP-1.

We report the isolation of TRIP-Br1, a transcriptional regulator that interacts with the PHD-bromodomain of co-repressors of Krüppel-associated box (KRAB)-mediated repression, KRIP-1(TIF1beta) and TIF1alpha, as well as the co-activator/adaptor p300/CBP. TRIP-Br1 and the related protein TRIP-Br2 possess transactivation domains. Like MDM2, which has a homologous transactivation domain, TRIP-Br proteins functionally contact DP-1, stimulating E2F-1/DP-1 transcriptional activity.

Deletion of cytosolic phospholipase A(2) suppresses Apc(Min)-induced tumorigenesis.

Although nonsteroidal antiinflammatory drugs (NSAIDs) show great promise as therapies for colon cancer, a dispute remains regarding their mechanism of action. NSAIDs are known to inhibit cyclooxygenase (COX) enzymes, which convert arachidonic acid (AA) to prostaglandins (PGs). Therefore, NSAIDs may suppress tumorigenesis by inhibiting PG synthesis.

Renal concentrating defect in mice lacking group IV cytosolic phospholipase A(2).

Eicosanoids regulate various cellular functions that are important in physiological and pathophysiological processes. Arachidonic acid is released from membranes by phospholipase A(2) (PLA(2)) activity. Activated macrophages derived from mice lacking the 85-kDa group IV cytosolic PLA(2) (cPLA(2)) have a markedly reduced release of prostaglandin E(2) and leukotrienes B(4) and C(4).

Recruiting participants for community-based research: the Diabetic Retinopathy Awareness Program.

Purpose: Recruiting participants is a major challenge for population studies. We present the recruitment methods followed by the Diabetic Retinopathy Awareness Program (DRAP), a community-based, randomized, masked, controlled trial to meet and exceed its sample size goals.

Methods: A county-wide multi-media promotional campaign to recruit and enroll participants in the trial was planned and executed from October 1993 through April 1994, with the assistance of the local news media and community and professional groups.

Detection of angiographically significant coronary artery disease with accelerated intermittent imaging after intravenous administration of ultrasound contrast material.

Background: Accelerated intermittent harmonic imaging (AII) is used to detect myocardial perfusion abnormalities after intravenous injection of ultrasound contrast medium. A low mechanical index and frame rates of 10 to 20 Hz are used to allow simultaneous wall motion analysis. The purpose of this study was to determine whether the myocardial contrast enhancement achieved with AII can be used to detect angiographically significant coronary artery disease during stress echocardiography.

Breast cancer and electromagnetic fields--a review.

Purpose: Several statements have been issued to the effect that no consistent, significant link has been demonstrated between cancer and electromagnetic fields (EMF). However, there continues to be much interest in a possible association with breast cancer, in part because breast cancer risk is substantially higher in industrialized countries than in other areas, and electric power generation and consumption is one of the hallmarks of industrialized societies. In 1987, Stevens proposed a biological mechanism whereby two products of electric power generation, EMF and light at night, might contribute to mammary carcinogenesis through inhibition of melatonin.

Etomidate and the osteocalcin response to gynaecological surgery.

Circulating osteocalcin is a good marker of osteoblastic activity and decreases significantly after stressful physiological states such as major surgery. Glucocorticoids are known to inhibit osteoblastic activity and result in a decline in circulating osteocalcin. We used etomidate to inhibit the cortisol response to routine gynaecological surgery to determine if this would prevent the postoperative decline in osteocalcin.

Magnetic field exposure assessment: a comparison of various methods.

The accurate and valid measurement of personal exposure to magnetic fields poses a major challenge for epidemiologic studies. When considering the various methods to assess exposure, it is unclear which measures are most relevant for studies of human disease, if any. Given these uncertainties, the Electromagnetic Fields and Breast Cancer on Long Island Study (EBCLIS) undertook a pilot study to develop the data collection protocol for a case-control study of breast cancer and magnetic fields.

A natural sobriety enzyme: a party pill or snake oil?

Promoters of a recently marketed "natural dietary supplement" called ALCOZYME claimed the product could rapidly and dramatically lower the blood ethanol concentration by metabolizing ethanol from the blood. We undertook a demonstration of the product in accordance with labeled instructions to replicate the results described by the manufacturer. We also tested ALCOZYME invitro in a solution of known ethanol concentration to determine whether the product directly degrades ethanol.

Expression of the transcriptional repressor protein Kid-1 leads to the disintegration of the nucleolus.

The rat Kid-1 gene codes for a 66-kDa protein with KRAB domains at the NH2 terminus and two Cys2His2-zinc finger clusters of four and nine zinc fingers at the COOH terminus. It was the first KRAB-zinc finger protein for which a transcriptional repressor activity was demonstrated. Subsequently, the KRAB-A domain was identified as a widespread transcriptional repressor motif.

Canadian Bardet-Biedl syndrome family reduces the critical region of BBS3 (3p) and presents with a variable phenotype.

There are at least five distinct Bardet-Biedl syndrome (BBS) loci, four of which have been mapped: 11q (BBS1), 16q (BBS2), 3p (BBS3), and 15q (BBS4). A comparative study of the three Arab-Bedouin kindreds used to map the BBS2, BBS3, and BBS4 loci suggests that the variability in the number and severity of clinical manifestations, particularly the pattern of polydactyly, reflects chromosome-specific subtypes of BBS [Carmi et al., 1995a; Am J Med Genet 59:199-203].

Adrenocortical disorders.

Preoperative preparation for the patient with adrenal disorders is directed toward restoring the intravascular volume and the electrolyte concentrations to normal. Hypertension and hypokalemia may be controlled by restricting sodium intake and administration of the aldosterone antagonist spironolactone. Patients taking steroids preoperatively must be adequately replaced throughout the perioperative phase at times of maximum stress.

In vivo dexamethasone effects on neutrophil effector functions in a rat model of acute lung injury.

Glucocorticoids, while potent antiinflammatory agents, have not been proven to be efficacious in Acute Respiratory Distress Syndrome, ARDS. Previous studies from this laboratory have reported that dexamethasone pretreatment of rats resulted in a 40-60% reduction in neutrophil influx into the airways following intratracheal administration of lipopolysaccharide, LPS. In the present study, the in vivo effects of dexamethasone on BAL neutrophil effector functions were evaluated by flow cytometry.

Reduced fertility and postischaemic brain injury in mice deficient in cytosolic phospholipase A2.

Phospholipase A2 (PLA2) enzymes are critical regulators of prostaglandin and leukotriene synthesis and can directly modify the composition of cellular membranes. PLA2 enzymes release fatty acids and lysophospholipids, including the precursor of platelet-activating factor, PAF, from phospholipids. Free fatty acids, eicosanoids, lysophospholipids and PAF are potent regulators of inflammation, reproduction and neurotoxicity.

Novel technique for coil embolization of intercostal branch of internal mammary artery graft.

Coronary artery steal resulting from a large unligated intercostal or pericardial side branch of the internal mammary artery graft causing postoperative angina has been previously described. Transcatheter coil occlusion of internal mammary artery side branch has successfully been performed to treat coronary steal syndrome. Unsuccessful deployment of the microcoils can be due to inadequate guiding support in the LIMA or prolapse of the delivery catheter in the side branch.