AMXI-5001, a novel dual parp1/2 and microtubule polymerization inhibitor for the treatment of human cancers.

Poly (ADP-ribose) polymerase (PARP) has recently emerged as a central mediator in cancer resistance against numerous anticancer agents to include chemotherapeutic agents such as microtubule targeting agents and DNA damaging agents. Here, we describe AMXI-5001, a novel, highly potent dual PARP1/2 and microtubule polymerization inhibitor with favorable metabolic stability, oral bioavailability, and pharmacokinetic properties. The potency and selectivity of AMXI-5001 were determined by biochemical assays.

Relationship between thioredoxin-interacting protein (TXNIP) and islet β-cell dysfunction in patients with impaired glucose tolerance and hypertriglyceridemia.

Aims: To study the relationship between thioredoxin-interacting protein (TXNIP) and pancreatic β-cell function in patients with impaired glucose regulation and patients with both impaired glucose regulation and hypertriglyceridemia.

Methods: We analyzed a population of 90 patients with impaired glucose regulation (IGR), 87 patients with IGR and hypertriglyceridemia, and 90 subjects with normal glucose tolerance (NGT). The levels of plasma TXNIP, a regulator of cellular oxidative stress, were measured.

Cardiovascular risk factors in Chinese American children: associations between overweight, acculturation, and physical activity.

Introduction: Understanding cardiovascular disease (CVD) risk factors among Chinese American children would allow us to target individuals in this group who are at the greatest risk for developing CVD early in life. The purpose of this study is to examine cardiovascular risk factors (increased blood pressure [BP], total cholesterol, low-density lipoproteins, triglycerides, decreased high-density lipoproteins, and increased body mass index [BMI]) in Chinese American children.

Method: A cross-sectional design was used.

Double-blind donepezil-placebo crossover augmentation study of atypical antipsychotics in chronic, stable schizophrenia: a pilot study.

Thirteen outpatients with chronic but stable schizophrenia received donepezil and placebo augmentation of their maintenance antipsychotic medication regimen. Each subject received in a randomized, counterbalanced order 1) donepezil 5 mg for 6 weeks then donepezil 10 mg for six weeks and 2) placebo donepezil for 12 weeks. Serial ratings of the Positive and Negative Symptom Scale (PANSS) [Kay, S.

The contribution of Medicaid managed care to the increasing undercount of Medicaid beneficiaries in the Current Population Survey.

Background: The Current Population Survey (CPS) is an important source of data for comparing beneficiaries across insurance groups. However, the CPS routinely underestimates the Medicaid population, and for unexplained reasons these underestimates have been increasing over time.

Objective: We sought to determine whether the penetration of Medicaid managed care is associated with the magnitude of the underestimate of Medicaid beneficiaries in the CPS using a pooled cross-sectional comparison of survey and administrative databases on all California Medicaid beneficiaries younger than 65 years of age.

Improving erectile function by silencing phosphodiesterase-5.

Purpose: We investigated whether phosphodiesterase-5 (PDE5) can be down-regulated by a specific small interfering RNA (siRNA) and whether this would improve erectile function.

Materials And Methods: A PDE5 siRNA encoding oligonucleotide was inserted into pSUPER-retro vector, resulting in the siRNA expressing construct, pPDE5-silencer. The construct was packaged into oncoretroviral particles and then transduced into rat cavernous smooth muscle cells (CSMCs).

Correlating phenotype and genotype in the periodic paralyses.

Background: Periodic paralyses and paramyotonia congenita are rare disorders causing disabling weakness and myotonia. Mutations in sodium, calcium, and potassium channels have been recognized as causing disease.

Objective: To analyze the clinical phenotype of patients with and without discernible genotype and to identify other mutations in ion channel genes associated with disease.

Appearance and distinguishing features of retroperitoneal calcifications at computed tomography.

Objectives: To describe the appearance of retroperitoneal calcifications seen at computed tomography (CT) and to investigate which CT features distinguish benign from malignant retroperitoneal calcifications.

Methods: We identified 25 patients with retroperitoneal calcifications by retrospective review of 39,931 abdominopelvic CT scans. Etiology of retroperitoneal calcifications was determined by examination of medical and histopathological records.

Development and destruction of the first state funded anti-smoking campaign in the USA.

Background: Minnesota was the first state in the USA to implement a large state funded tobacco control programme (in 1985). Despite evidence of effectiveness, it was dismantled in 1993.

Objective: To describe and analyse how and why these events transpired and identify lessons for tobacco control advocates facing similar challenges in the 21st century.

Burst fracture in the metastatically involved spine: development, validation, and parametric analysis of a three-dimensional poroelastic finite-element model.

Study Design: A finite-element study and in vitro experimental validation was performed for a parametric investigation of features that contribute to burst fracture risk in the metastatically involved spine.

Objectives: To develop and validate a three-dimensional poroelastic model of a metastatically compromised vertebral segment, to evaluate the effect of lytic lesions on vertebral strains and pressures, and to determine the influence of loading and motion segment status (bone density, pedicle involvement, disc degeneration, and tumor size) on the relative risk of burst fracture initiation.

Summary Of Background Data: Finite-element analysis has been used successfully to predict failure loads and fracture patterns for bone.

In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid leukemia.

Recent reports have established the prenatal origin of leukemia translocations and resultant fusion genes in some patients, including MLL-AF4 translocations in infants and TEL-AML1 translocations in children. We now report evidence for the prenatal origin of a translocation in childhood acute myeloid leukemia (AML). The t(8;21) AML1-ETO translocations were sequenced at the genomic level in 10 diagnostic leukemia samples from children with available neonatal Guthrie blood spots.

Advanced diagnostic methods in oral and maxillofacial pathology. Part I: molecular methods.

The practice of pathology is currently undergoing significant change, in large part due to advances in the analysis of DNA, RNA, and proteins in tissues. These advances have permitted improved biologic insights into many developmental, inflammatory, metabolic, infectious, and neoplastic diseases. Moreover, molecular analysis has also led to improvements in accuracy of disease diagnosis and classification.

Multisection dynamic CT perfusion for acute cerebral ischemia: the "toggling-table" technique.

A new CT perfusion technique providing extended anatomic coverage was evaluated in 12 patients with suspected acute middle cerebral artery ischemia. With a multidetector CT scanner, scans were obtained in an alternating fashion at two distinct "toggling" table positions (two 1-cm sections each) during a 40-mL contrast agent bolus (approximately 5 seconds per image), and perfusion parameter maps were created. The CT perfusion results were compared with follow-up images.

Evaluation of fetal heart dimensions from 12 weeks to term.

To evaluate whether fetal cardiac measurements can be made in the second trimester, we examined a cohort of normal pregnancies between 12 and 18 weeks' gestation using state-of-the-art ultrasound equipment. We examined this population longitudinally at intervals of 2 weeks, as well as at 32 weeks' gestation. From the 4-chamber view we measured the ventricular and atrial cavity dimensions, the thickness of the ventricular walls and septum at end-diastole, and the annulus dimensions of the mitral and tricuspid valves.

Endovascular repair of abdominal aortic aneurysm using a pararenal fenestrated stent-graft.

Purpose: To report an unusual case of endovascular abdominal aortic aneurysm (AAA) exclusion in which a fenestrated stent-graft was used to seal a proximal Type I endoleak.

Methods And Results: An 84-year-old man with a 6.0-cm AAA underwent an aortomonoiliac aneurysm exclusion procedure that was complicated by a proximal endoleak.

The impact of race on freedom from prostate-specific antigen failure in prostate cancer patients treated with definitive radiation therapy.

Many studies have reported that African-American men have the highest incidence and mortality rates for prostate cancer in the United States. A retrospective analysis of 607 patients treated with definitive radiation therapy was performed at the University of California San Francisco and its affiliated hospitals between 1987 and 1995. The patient population analyzed included African-American, Caucasian, and Asian men with AJCC T1-T3 disease.

Pretreatment prostate-specific antigen and Gleason score predict the risk of extracapsular extension and the risk of failure following radiotherapy in patients with clinically localized prostate cancer.

The purpose of this study is to evaluate the use of a relatively simple equation for predicting the risk of extracapsular extension (ECE) based on the pretreatment prostate-specific antigen (PSA) and Gleason score (GS) in patients with clinically localized prostate cancer. Three hundred and seventy-four patients who underwent radical prostatectomy between 1988 and 1994 and 521 men undergoing definitive radiotherapy during a similar time period were eligible for this analysis. Surgically treated patients were considered eligible if the pathological stage, preoperative PSA, and GS were available.

Management of intravaginal warts in women with 5-fluorouracil (1%) in vaginal hydrophilic gel: a placebo-controlled double-blind study.

The purpose of this placebo-controlled, double-blind study was to determine the safety, tolerability and clinical efficacy of 5-fluorouracil (1%) in a vaginal hydrophilic gel (hydroxyethylcellulose, 1%) to cure intravaginal papillomas in women. Pre-selected, 60 women ranging between 18 and 50 years of age (mean 24.6), having 312 vaginal condylomas (mean 5.

Development of a classification system for periodontal diseases and conditions.

Classification systems are necessary in order to provide a framework in which to scientifically study the etiology, pathogenesis, and treatment of diseases in an orderly fashion. In addition, such systems give clinicians a way to organize the health care needs of their patients. The last time scientists and clinicians in the field of periodontology and related areas agreed upon a classification system for periodontal diseases was in 1989 at the World Workshop in Clinical Periodontics.

AFM study of citric acid-ferric chloride etching characteristics of dentin.

Purpose: To determine the etching characteristics of 10% citric acid etchant with 3% ferric chloride (10-3) compared with related etchants without ferric chloride (10-0), or one of similar pH (36% citric acid).

Materials And Methods: Atomic force microscopy (AFM) was used to measure the surface recession and morphology of dentin. AFM images were taken of the same samples at seven steps of an etching and drying procedure using 10-3 (pH = 1.

Novel role for the nuclear phosphoprotein SET in transcriptional activation of P450c17 and initiation of neurosteroidogenesis.

Neurosteroids are important endogenous regulators of gamma-aminobutryic acid (GABA(A)) and N-methyl-D-aspartate (NMDA) receptors and also influence neuronal morphology and function. Neurosteroids are produced in the brain using many of the same enzymes found in the adrenal and gonad. The crucial enzyme for the synthesis of DHEA (dehydroepiandrosterone) in the brain is cytochrome P450c17.