Soluble fms-like tyrosine kinase 1 is increased in preeclampsia but not in normotensive pregnancies with small-for-gestational-age neonates: relationship to circulating placental growth factor.

Context: An excess of the soluble receptor, fms-like tyrosine kinase 1 (sFlt-1) may contribute to maternal vascular dysfunction in women with preeclampsia by binding and thereby reducing concentrations of free vascular endothelial growth factor and placental growth factor (PlGF) in the circulation. The putative stimulus for increased sFlt-1 during preeclampsia, placental hypoxia due to poor perfusion, is common to both preeclampsia and idiopathic intrauterine growth restriction. However, the latter condition occurs without maternal vascular disease.

Provider type and depression treatment adequacy.

We investigate the effect of initial provider (psychiatrist versus primary care physician or non-physician mental health specialist) on the adequacy of subsequent treatment for persons with depression. Our data are from MarketScan, a medical and pharmacy insurance claims database, which we use to estimate models of the likelihood of treatment for depression and the likelihood that any anti-depression treatments received are adequate. Patients initially seeing psychiatrists are most likely to receive adequate treatment.

Distal spinal and bulbar muscular atrophy caused by dynactin mutation.

Impaired axonal transport has been postulated to play a role in the pathophysiology of multiple neurodegenerative disorders. In this report, we describe the results of clinical and neuropathological studies in a family with an inherited form of motor neuron disease caused by mutation in the p150Glued subunit of dynactin, a microtubule motor protein essential for retrograde axonal transport. Affected family members had a distinct clinical phenotype characterized by early bilateral vocal fold paralysis affecting the adductor and abductor laryngeal muscles.

An integrated platform for automated analysis of protein NMR structures.

Recent developments provide automated analysis of NMR assignments and three-dimensional (3D) structures of proteins. These approaches are generally applicable to proteins ranging from about 50 to 150 amino acids. In this chapter, we summarize progress by the Northeast Structural Genomics Consortium in standardizing the NMR data collection process for protein structure determination and in building an integrated platform for automated protein NMR structure analysis.

Determining the optimal size of small molecule mixtures for high throughput NMR screening.

High-throughput screening (HTS) using NMR spectroscopy has become a common component of the drug discovery effort and is widely used throughout the pharmaceutical industry. NMR provides additional information about the nature of small molecule-protein interactions compared to traditional HTS methods. In order to achieve comparable efficiency, small molecules are often screened as mixtures in NMR-based assays.

Human identification from the ankle with pre- and postsurgical radiographs.

Fifty-four sets of presurgical ("premortem") and postsurgical ("postmortem") foot and ankle radiographs were retrospectively evaluated to simulate a postmortem identification. The entire foot and ankle was examined in a previous study. The present study evaluates only the ankle for positive identification.

Extractable bone morphogenetic protein and correlation with induced new bone formation in an in vivo assay in the athymic mouse model.

A correlation between extractable bone morphogenetic proteins (BMPs) in demineralized bone matrix (DBM) and osteoinduction has been suggested. Extractable BMP-4 and osteoinductivity of DBM from 40 donors were assessed using enzyme-linked immunosorbent assay (ELISA) and in vivo athymic mouse assay, respectively. Extractable BMP-4 level averaged 3.

Association of body mass index, age, and cigarette smoking with serum testosterone levels in cycling women undergoing in vitro fertilization.

Objective: [1] To examine the effects of body mass index (BMI), age, cigarette smoking, cause of infertility, and use of oral contraceptives on baseline serum testosterone (T), and [2] to examine associations between baseline serum T and IVF outcomes such as pre-hCG serum E(2), number of oocytes retrieved, oocyte fertilization rate, and pregnancy outcome in regularly cycling women.

Design: Prospective, cohort study.

Setting: Three IVF programs in eastern Massachusetts.

Protein NMR recall, precision, and F-measure scores (RPF scores): structure quality assessment measures based on information retrieval statistics.

One of the most important challenges in modern protein NMR is the development of fast and sensitive structure quality assessment measures that can be used to evaluate the "goodness-of-fit" of the 3D structure with NOESY data, to indicate the correctness of the fold and accuracy of the resulting structure. Quality assessment is especially critical for automated NOESY interpretation and structure determination approaches. This paper describes new NMR quality assessment scores, including Recall, Precision, and F-measure scores (referred to here are "NMR RPF" scores), which quickly provide global measures of the goodness-of-fit of the 3D structures with NOESY peak lists using methods from information retrieval statistics.

Contributions of the input signal and prior activation history to the discharge behaviour of rat motoneurones.

The principal computational operation of neurones is the transformation of synaptic inputs into spike train outputs. The probability of spike occurrence in neurones is determined by the time course and magnitude of the total current reaching the spike initiation zone. The features of this current that are most effective in evoking spikes can be determined by injecting a Gaussian current waveform into a neurone and using spike-triggered reverse correlation to calculate the average current trajectory (ACT) preceding spikes.

Avenues to prestige among adolescents in public and religiously affiliated high schools.

We used data from 1,733 college students to explore whether adolescents' avenues to prestige differ in public and private high schools. Students attending seven large universities during the 1997--98 academic year provided information on the ways in which adolescents in their high schools had gained prestige with peers. The analyses revealed no differences by high school type for girls, with the exception of greater emphasis on clothes in public schools as compared with private schools.

Contribution of persistent sodium currents to spike-frequency adaptation in rat hypoglossal motoneurons.

In response to constant current inputs, the firing rates of motoneurons typically show a continuous decline over time. The biophysical mechanisms underlying this process, called spike-frequency adaptation, are not well understood. Spike-frequency adaptation normally exhibits a rapid initial phase, followed by a slow, later phase that continues throughout the duration of firing.

Investigation of elderly deaths in nursing homes by the medical examiner over a year.

Despite death being one of the most common reasons for discharge from a nursing home, fewer than 1% of nursing home resident deaths are autopsied. To evaluate our role as medical examiner in nursing home deaths, we conducted a retrospective review of all decedents in Jefferson County, Alabama, for the year 2001. Death certificate data indicate that 995 deaths occurred in nursing homes in Jefferson County in 2001.

The application of x-ray, NMR, and molecular modeling in the design of MMP inhibitors.

The following review discusses the successful application of X-ray, NMR, and molecular modeling in the design of potent and selective inhibitors of matrix metalloproteinases (MMPs) and TNFalpha-converting enzyme (TACE) from Wyeth. The importance of protein and ligand mobility as it impacts structure-based design is also discussed. The MMPs are an active target for a variety of diseases, including cancer and arthritis.

Preclinical validation of anti-TMEFF2-auristatin E-conjugated antibodies in the treatment of prostate cancer.

Current treatments for advanced stage, hormone-resistant prostate cancer are largely ineffective, leading to high patient mortality and morbidity. To fulfill this unmet medical need, we used global gene expression profiling to identify new potential antibody-drug conjugate (ADC) targets that showed maximal prostate cancer-specific expression. TMEFF2, a gene encoding a plasma membrane protein with two follistatin-like domains and one epidermal growth factor-like domain, had limited normal tissue distribution and was highly overexpressed in prostate cancer.

Moderate hyperhomocysteinemia decreases endothelial-dependent vasorelaxation in pregnant but not nonpregnant mice.

Increased homocysteine is associated with the pregnancy complication preeclampsia and with later-life cardiovascular disease. Although elevated homocysteine persists after pregnancy, the vascular changes of preeclampsia abate with delivery, and cardiovascular disease occurs decades later. This suggests the vasculature during pregnancy may manifest increased sensitivity to homocysteine.

Identification of novel estrogen receptor alpha antagonists.

We have identified novel estrogen receptor alpha (ERalpha) antagonists using both cell-based and computer-based virtual screening strategies. A mammalian two-hybrid screen was used to select compounds that disrupt the interaction between the ERalpha ligand binding domain (LBD) and the coactivator SRC-3. A virtual screen was designed to select compounds that fit onto the LxxLL peptide-binding surface of the receptor, based on the X-ray crystal structure of the ERalpha LBD complexed with a LxxLL peptide.

Prevention and treatment of nosocomial sepsis in the NICU.

Nosocomial sepsis is a serious problem for neonates who are admitted for intensive care. It is associated with an increase in mortality, morbidity, and prolonged length of hospital stay. Thus, both the human and fiscal costs of these infections are high.

Nosocomial infection in the NICU: a medical complication or unavoidable problem?

Nosocomial sepsis is a serious problem for neonates who are admitted for intensive care. As it is associated with increases in mortality, morbidity, and prolonged length of hospital stay, both the human and fiscal costs of these infections are high. Although the rate of nosocomial sepsis increases with the degree of both prematurity and low birth weight, no specific lab test has been shown to be very useful in improving our ability to predict who has a "real" blood-stream infection and, therefore, who needs to be treated with a full course of antibiotics.

Homocysteine and folic acid are inversely related in black women with preeclampsia.

Black women have an increased risk of preeclampsia compared with white women. Plasma homocysteine is increased in preeclampsia. Homocysteine concentrations are affected by nutritional deficiencies, particularly decreased folic acid and B12, leading to increased homocysteine.

Renal handling of homocysteine during normal pregnancy and preeclampsia.

Objective: Maternal plasma homocysteine decreases in normal pregnancy and is significantly increased in preeclampsia. The goal of this study was to investigate the role of the maternal kidney in the changes of plasma homocysteine during normal pregnancy and preeclampsia.

Methods: Plasma and 24-hour urine samples were collected in the same women before, during (first, second, and third trimesters), and after normal pregnancy; and in a separate cross-sectional study of normal pregnant, preeclamptic and nonpregnant women and homocysteine concentrations were measured.

Human progesterone receptor polymorphisms and implantation failure during in vitro fertilization.

Objective: Polymorphic variants of the human progesterone receptor gene have been described, but their potential influence on in vitro fertilization outcome have not been studied.

Study Design: DNA was available from 317 women (cases) who had >or=2 embryo transfers without a clinical pregnancy and from 288 women (control subjects) who became pregnant after 1 in vitro fertilization attempt. With protocols that were specific for H770H (C/T genotype) and +331G/A polymorphism, amplification of polymorphism fragments, digestion with restriction enzymes, and gel visualization were performed.

Psychotherapy and pharmacotherapy in depression.

Background: Depression is a condition with various modes of treatment, including pharmacotherapy, psychotherapy, and some combination of each. The role of psychotherapy in the treatment of depression relative to the role of pharmacotherapy is not well understood, and guidelines for psychotherapy in the primary care setting differ from guidelines for specialty care. There is little evidence concerning circumstances in actual practice that affect the use of psychotherapy in conjunction with pharmacotherapy.