Detection and confirmation of reptilian adenovirus infection by in situ hybridization.

Adenovirus infections are documented in at least 12 different species of reptiles. In contrast to their mammalian and avian counterparts reptilian adenoviruses are not well characterized as to their pathogenic potential and their ability to cause primary disease. In the diagnostic setting, fresh tissues are often not available for virus isolation, and the confirmation of reptilian adenovirus infections is dependent largely upon electron microscopy for the identification of intranuclear viral inclusions associated with histopathologic changes.

Breast implants and cancer: causation, delayed detection, and survival.

Concern for many women with breast implants has been focused on three topics: cancer (both breast and other cancers), delayed detection of breast cancer, and increased breast cancer recurrence or decreased length of survival. In this study, a qualitative review of the literature on these subjects was conducted, coupled with a meta-analysis of the risk for breast cancer or other cancers (excluding that of the breast). Researchers have consistently found no persuasive evidence of a causal association between breast implants and any type of cancer.

Pathobiology of A/chicken/Hong Kong/220/97 (H5N1) avian influenza virus in seven gallinaceous species.

Direct bird-to-human transmission, with the production of severe respiratory disease and human mortality, is unique to the Hong Kong-origin H5N1 highly pathogenic avian influenza (HPAI) virus, which was originally isolated from a disease outbreak in chickens. The pathobiology of the A/chicken/Hong Kong/220/97 (H5N1) (HK/220) HPAI virus was investigated in chickens, turkeys, Japanese and Bobwhite quail, guinea fowl, pheasants, and partridges, where it produced 75-100% mortality within 10 days. Depression, mucoid diarrhea, and neurologic dysfunction were common clinical manifestations of disease.

Nuclear import of activated D-ERK by DIM-7, an importin family member encoded by the gene moleskin.

The initiation of gene expression in response to Drosophila receptor tyrosine kinase signaling requires the nuclear import of the MAP kinase, D-ERK. However, the molecular details of D-ERK translocation are largely unknown. In this regard, we have identified D-Importin-7 (DIM-7), the Drosophila homolog of vertebrate importin 7, and its gene moleskin.

Identification of genomic regions that interact with a viable allele of the Drosophila protein tyrosine phosphatase corkscrew.

Signaling by receptor tyrosine kinases (RTKs) is critical for a multitude of developmental decisions and processes. Among the molecules known to transduce the RTK-generated signal is the nonreceptor protein tyrosine phosphatase Corkscrew (Csw). Previously, Csw has been demonstrated to function throughout the Drosophila life cycle and, among the RTKs tested, Csw is essential in the Torso, Sevenless, EGF, and Breathless/FGF RTK pathways.

Quality of measurement of smoking status by self-report and saliva cotinine among pregnant women.

Objective: The objectives of this paper were to determine the rate of misclassification of smoking and nonsmoking status by self-reports and saliva continine of pregnant women participating in a smoking cessation trial, determine the relationship of the number of cigarettes smoked per day and saliva continine, and examine whether misclassification was due to an inappropriate saliva continine cutoff point.

Methods: End of pregnancy self-reports of smoking status and saliva continine were used to calculate misclassification rates.

Results: The findings revealed that 61 of 441 self-reported smokers had biochemical values inconsistent with smoking status for a smoking misclassification rate of 13.

Determination of hexazinone in groundwater by direct-injection high-performance liquid chromatography.

Hexazinone has been detected at levels ranging from 0.2 to 50 micrograms/L in many groundwater samples from eastern Maine over the past decade. A rapid and inexpensive direct-injection high-performance liquid chromatographic (HPLC) method has been developed to monitor contamination levels of the herbicide.

Human beta3 adrenergic receptor agonists containing imidazolidinone and imidazolone benzenesulfonamides.

The cyclopentylpropylimidazolidinone L-766,892 is a potent beta3 AR agonist (EC50 5.7 nM, 64% activation) with 420- and 130-fold selectivity over binding to the beta1 and beta2 ARs, respectively. In anesthetized rhesus monkeys, L-766,892 elicited dose-dependent hyperglycerolemia (ED50 0.

Human beta3 adrenergic receptor agonists containing cyclic ureidobenzenesulfonamides.

Human beta3 adrenergic receptor agonists containing 5-membered ring ureas were shown to be potent partial agonists with excellent selectivity over beta1 and beta2 binding. L-760,087 (4a) and L-764,646 (5a) (beta3 EC50 = 18 and 14 nM, respectively) stimulate lipolysis in rhesus monkeys (ED50 = 0.2 and 0.

Quantitative variations in the level of MAPK activity control patterning of the embryonic termini in Drosophila.

We have examined the role in patterning of quantitative variations of MAPK activity in signaling from the Drosophila Torso (Tor) receptor tyrosine kinase (RTK). Activation of Tor at the embryonic termini leads to differential expression of the genes tailless and huckebein. We demonstrate, using a series of mutations in the signal transducers Corkscrew/SHP-2 and D-Raf, that quantitative variations in the magnitude of MAPK activity trigger both qualitatively and quantitatively distinct transcriptional responses.

The importance of cerebrospinal fluid lactate in the evaluation of congenital lactic acidosis.

In 27 of 28 children with congenital lactic acidosis, cerebrospinal fluid lactate was higher than venous blood lactate. The mean +/- SEM difference between these variables was 2.4 +/- 0.

3-Pyridyloxypropanolamine agonists of the beta 3 adrenergic receptor with improved pharmacokinetic properties.

Pyridyloxypropanolamines L-749,372 (8, beta 3 EC50 = 3.6 nM) and L-750,355 (29, beta 3 EC50 = 13 nM) are selective partial agonists of the human receptor, with 33% and 49% activation, respectively. Both stimulate lipolysis in rhesus monkeys (ED50 = 2 and 0.

Potent, selective benzenesulfonamide agonists of the human beta 3 adrenergic receptor.

A cloned human beta 3 adrenergic receptor assay was used to identify phenoxypropanolamine agonist 1. SAR studies led to the identification of benzenesulfonamide derivative 20, a 6.3 nM beta 3 agonist which shows 30-fold selectivity for beta 3 agonist activity over beta 1 and beta 2 receptor binding.

Clinical utility of troponin T levels and echocardiography in the emergency department.

We investigated the clinical utility of cardiac troponin T (TnT) and echocardiography in the emergency department to predict subsequent in-hospital diagnosis and adverse cardiac events. TnT is a cardiac-specific protein released during cell injury such as that following acute myocardial inFarction (MI). Unlike creatine kinase-MB isoenzymes, TnT is increased in a subset of patients with unstable angina, and these may be at higher risk for subsequent cardiac events.

The three-dimensional solution structure of the SRC homology domain-2 of the growth factor receptor-bound protein-2.

A set of high-resolution three-dimensional solution structures of the Src homology region-2 (SH2) domain of the growth factor receptor-bound protein-2 was determined using heteronuclear NMR spectroscopy. The NMR data used in this study were collected on a stable monomeric protein solution that was free of protein aggregates and proteolysis. The solution structure was determined based upon a total of 1439 constraints, which included 1326 nuclear Overhauser effect distance constraints, 70 hydrogen bond constraints, and 43 dihedral angle constraints.

Estimating a relative risk across sparse case-control and follow-up studies: a method for meta-analysis.

Meta-analysis is the quantitative technique of combining results from different studies. There is a variety of procedures available for combining effect measures across epidemiologic studies. None of these methods provides an overall effect estimate when the data are sparse within studies and come from different study designs.

Ras oncoprotein inhibitors: the discovery of potent, ras nucleotide exchange inhibitors and the structural determination of a drug-protein complex.

The nucleotide exchange process is one of the key activation steps regulating the ras protein. This report describes the development of potent, non-nucleotide, small organic inhibitors of the ras nucleotide exchange process. These inhibitors bind to the ras protein in a previously unidentified binding pocket, without displacing bound nucleotide.