Responsiveness of the aging circadian clock to light.

The present study assessed whether advances in sleep times and circadian phase in older adults might be due to decreased responsiveness of the aging circadian clock to light. Sixteen young (29.3+/-5.

Detection of nitrous oxide in the neuronal nitric oxide synthase reaction by gas chromatography-mass spectrometry.

Using headspace gas chromatography-mass spectrometry, we detected significant amounts of nitrous oxide in the reaction products of the monooxygenase reaction catalyzed by neuronal nitric oxide synthase. Nitrous oxide is a dimerization product of nitroxyl anion; its presence in the reaction products indicates that the nitroxyl anion is a product of the neuronal nitric oxide synthase-catalyzed reaction.

A theoretical framework for understanding help-seeking processes among survivors of intimate partner violence.

This paper suggests a conceptual framework for understanding the processes of help-seeking among survivors of intimate partner violence (IPV). A cognitive theory from general literature on help-seeking in "stigmatizing" situations suggests three relevant processes or stages of seeking help in the IPV context: defining the problem, deciding to seek help, and selecting a source of support. Individual, interpersonal, and sociocultural factors that influence decision-making at each of these stages are discussed and illustrated with case examples.

Identification of phosphorylation sites in insulin receptor substrate-1 by hypothesis-driven high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.

Serine phosphorylation of insulin receptor substrate-1 (IRS-1) can regulate tyrosine phosphorylation of IRS-1 and subsequent insulin signaling. The 182 serine and 60 threonine residues in IRS-1 make position-by-position analysis of potential phosphorylation sites by mutagenesis difficult. Tandem mass spectrometry provides a more efficient way to identify phosphorylated residues in IRS-1.

The "zoom lens" of focal attention in visual search: changes in aging and Alzheimer's disease.

Visual search for a target in an array of distractors relies upon flexible shifts between global and local modes of attentional processing. Visual search is slowed in patients with Alzheimer's disease (AD), in part due to an increase in the number and duration of eye fixations made en route to a target (Rösler et al., 2000).

Identification of insulin receptor substrate 1 serine/threonine phosphorylation sites using mass spectrometry analysis: regulatory role of serine 1223.

Insulin receptor substrate 1 (IRS-1), an intracellular substrate of the insulin receptor tyrosine kinase, also is heavily phosphorylated on serine and threonine residues, and several serine phosphorylation sites alter the function of IRS-1. Because of the large number of serine/threonine residues, position-by-position analysis of these potential phosphorylation sites by mutagenesis is difficult. To circumvent this, we have employed matrix-assisted laser desorption/ionization time-of-flight and HPLC-electrospray ionization tandem mass spectrometry techniques to scan for serine and threonine residues that are phosphorylated in full-length human IRS-1 ectopically expressed in cells using an adenoviral vector.

A moderate reduction of Bcl-x(L) expression protects against tumorigenesis; however, it also increases susceptibility to tissue injury.

Little consideration has been given to the possibility that there could be variations in protein expression that alter susceptibility to tumorigenesis without causing other obvious phenotypic effects. Therefore, we sought to determine if haploinsufficiency for the anti-apoptotic protein Bcl-x(L) would affect tumorigenesis. We chose to study Bcl-x(L) because although bcl-x+/- mice were thought to be phenotypically normal, we and others found that haploinsufficiency for Bcl-x(L) lowers fibroblast resistance to apoptosis in tissue culture.

CT-angiography for the detection of a lower gastrointestinal bleeding source.

The evaluation of lower gastrointestinal bleeding (LGIB) often involves the collaborative efforts of the gastroenterologist, radiologist, and surgeon. Efforts to localize the acute LGIB have traditionally involved colonoscopy, technetium-labeled red blood cell (RBC) scintigraphy, angiography, or a combination of these modalities. The sensitivity of each method of diagnosis is limited, with the most common cause of a negative study the spontaneous cessation of hemorrhage.

Phosphorylation of Grb10 by mitogen-activated protein kinase: identification of Ser150 and Ser476 of human Grb10zeta as major phosphorylation sites.

Grb10 is a Src-homology 2 (SH2) and Pleckstrin-homology (PH) domain-containing protein that binds to several autophosphorylated receptor tyrosine kinases including the insulin receptor (IR). Our previous studies showed that Grb10 underwent insulin-stimulated serine phosphorylation, yet the kinase(s) responsible for phosphorylation and the sites of the phosphorylation remain unknown. In this report, we show that Grb10 is a direct substrate of the p42/44 mitogen-activated protein kinase (MAPK).

Primary progressive aphasia: reversed asymmetry of atrophy and right hemisphere language dominance.

Primary progressive aphasia (PPA) is almost always associated with asymmetrical left hemisphere degeneration. The authors report that right hemisphere atrophy in a patient with PPA was associated with atypical right hemisphere dominance for language. This suggests that neuronal damage in PPA is therefore tightly linked to the underlying anatomy of the language network.

Paradoxical features of word finding difficulty in primary progressive aphasia.

Impaired word retrieval is a main symptom of primary progressive aphasia (PPA). The cognitive features of this impairment in PPA are poorly understood. We studied 12 patients with PPA (6 English-speaking and 6 Dutch-speaking), 7 patients with early-stage clinically probable Alzheimer's disease (PRAD), 5 patients with mild cognitive impairment (MCI), and 15 age-matched, cognitively intact, control subjects.

Oxidative modifications and aggregation of Cu,Zn-superoxide dismutase associated with Alzheimer and Parkinson diseases.

Although oxidative stress has been strongly implicated in the pathogenesis of Alzheimer disease (AD) and Parkinson disease (PD), the identities of specific protein targets of oxidative damage remain largely unknown. Here, we report that Cu,Zn-superoxide dismutase (SOD1), a key antioxidant enzyme whose mutations have been linked to autosomal dominant neurodegenerative disorder familial amyotrophic lateral sclerosis (ALS), is a major target of oxidative damage in AD and PD brains. By using a combination of two-dimensional gel electrophoresis, immunoblot analysis, and mass spectrometry, we have identified four human brain SOD1 isoforms with pI values of 6.

The Activities of Daily Living Questionnaire: a validation study in patients with dementia.

This study describes the development and validation of the Activities of Daily Living Questionnaire (ADLQ), an informant-based assessment of functional abilities, in patients with probable Alzheimer disease and other forms of dementia. The ADLQ measures functioning in six areas: self-care, household care, employment and recreation, shopping and money, travel, and communication. The ADLQ was administered to 140 caregivers followed longitudinally in the Northwestern Alzheimer's Disease Center.

Preservation of reasoning in primary progressive aphasia: further differentiation from Alzheimer's disease and the behavioral presentation of frontotemporal dementia.

Primary Progressive Aphasia (PPA) is a clinical dementia syndrome characterized by the gradual dissolution of language without impairment of other cognitive domains for at least the first 2 years of illness (M.-M. Mesulam, 1982, 2001).

Gamma-guided diagnostic peritoneal lavage for detection of bowel perforation.

Hypothesis: Bowel perforation can be diagnosed by detection of orally administered technetium Tc 99m sulfur colloid ((99m)Tc SC) in diagnostic peritoneal lavage (DPL) fluid using a handheld gamma-detection probe.

Design: A canine intestinal-injury model was used to test the hypothesis. The (99m)Tc SC (55.

Apolipophorin-III-like protein expressed in the antenna of the red imported fire ant, Solenopsis invicta Buren (Hymenoptera: Formicidae).

Antennal proteins of the male fire ant (Solenopsis invicta) were analyzed by two-dimensional gel electrophoresis, with the objective of identifying pheromone-binding proteins, which have not previously been found in ant antennae. The major low-molecular weight protein found in the male fire ant antenna was subjected to Edman degradation to determine the N-terminal amino acid sequence. Degenerate PCR primers based on this sequence were used to obtain a cDNA sequence corresponding to the full-length protein sequence.

Inhibition of mitogenic signaling and induction of apoptosis in human bladder smooth muscle cells treated with doxazosin.

Purpose: The alpha1 antagonist doxazosin is used to treat lower urinary tract symptoms and is believed to function primarily as a smooth muscle relaxant. However, doxazosin has been shown to inhibit proliferation and induce apoptosis in nonbladder smooth muscle. Consequently, we examined the effects of doxazosin on human bladder smooth muscle cell (SMC) proliferation and apoptosis.

Early N-terminal changes and caspase-6 cleavage of tau in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive amnestic dementia that involves post-translational hyperphosphorylation, enzymatic cleavage, and conformational alterations of the microtubule-associated protein tau. The truncation state of tau influences many of its pathologic characteristics, including its ability to assume AD-related conformations and to assemble into filaments. Cleavage also appears to be an important marker in AD progression.

Treatment of superior mesenteric and portal vein thrombosis with direct thrombolytic infusion via an operatively placed mesenteric catheter.

Acute superior mesenteric vein (SMV) and portal vein (PV) thrombosis can be a complication of hypercoagulable, inflammatory, or infectious states. It can also occur as a complication of medical or surgical intervention. Management of mesenteric and portal vein thrombosis includes both operative and nonoperative approaches.

Cholinergic nucleus basalis tauopathy emerges early in the aging-MCI-AD continuum.

The cholinergic denervation in Alzheimer's disease (AD) provides the rationale for treatments with anticholinesterases. The presence of this cholinergic lesion is solidly established in advanced AD. Whether it also exists in early disease remains unsettled.

Proteomic identification of specific oxidized proteins in ApoE-knockout mice: relevance to Alzheimer's disease.

We have examined oxidized proteins in the brain regions of wild-type (WT) and ApoE-knockout (KO) animals. Total protein oxidation in the hippocampus of young-KO (6 month) animals was approximately 2-fold greater than that of young-WT (6 month) animals and was similar to that of old-WT (18 month) and old-KO (18 month) animals. In the cortex of the same animals, the levels of total protein oxidation in all four groups were not significantly different.

Analysis of proteins stained by Alexa dyes.

Alexa dye staining of proteins is used for the fluorescence microscopy of single particles that are sometimes multimolecular protein complexes. To characterize the staining, post-staining determination must be made of which protein(s) in a complex have been Alexa-stained. The present communication describes the use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) for performing this determination.

[Magnetic resonance studies in Alzheimer's dementia. What routine scanning shows].

Magnetic resonance images of the brain acquired in relationship to the commissural plane have been analyzed in twenty cases classified as Probable Alzheimer's disease (Pr. AD). These examinations have been compared to normal aged matched subjects.