Changes in neuropsychiatric symptoms as outcome measures in clinical trials with cholinergic therapies for Alzheimer disease.

Alzheimer disease (AD) is a multifaceted disorder with primary manifestations involving neuropsychologic, neuropsychiatric, and neurologic domains. These primary disturbances are based on brain dysfunction and produce secondary effects on patient activities of daily living and quality of life, and have adverse consequences for caregivers, family members, and society. Apathy, agitation, mood disturbances, irritability, disinhibition, delusions, aberrant motor behavior, and abnormalities of sleep and eating are common in AD.

Identification of inflammatory mediators by screening for glucocorticoid-attenuated response genes.

We describe an approach for identifying novel inflammatory mediators, based on screening for immediate early/primary response genes whose induction by an inflammatory stimulus is attenuated by glucocorticoids. This procedure can be applied to a wide range of cell types and tissues, using a variety of inducers. In an initial test of this idea, we identified cDNAs for 12 LPS-induced, glucocorticoid-attenuated response genes (GARGs) by differential hybridization screening of a lambda phage cDNA library from murine 3T3 fibroblasts.

Axonal proteins involved in myelination: characterization of a collagen-like protein.

An anti-axolemma monoclonal antibody, designated G21.3, has been isolated in order to understand molecular mechanisms involved in myelination. Both biochemical and morphological studies showed that the monoclonal antibody inhibits myelin production by oligodendrocytes in cerebellar slice cultures.

X-ray phototherapy for canine brain masses.

Brain masses diagnosed in 47 pet dogs as tumors by CT scans, and confirmed in 12 dogs by necropsies, were injected with iodinated contrast media and treated by a modified CT scanner, the CTRx. Twenty-six dogs that received six or more weekly treatments of about 5.6 Gy per fraction, of which about 25% was contributed by radiation from the iodine, for a median total dose of 39 Gy, had a median survival of 230 days.

A three-dimensional multimodality brain map of the nemestrina monkey.

A three-dimensional multimodality computerized map of the nemestrina monkey brain was created with serial sectioning and digital imaging techniques. An adult female Macaca nemestrina (pigtail macaque) weighing 7.2 kg was used in constructing this atlas.

Granule cell mRNA levels for BDNF, NGF, and NT-3 correlate with neuron losses or supragranular mossy fiber sprouting in the chronically damaged and epileptic human hippocampus.

This study determined in temporal lobe epilepsy patients if there were correlations among hippocampal granule cell expression of neurotrophin mRNAs, aberrant supragranular mossy fiber sprouting, and neuron losses. Consecutive surgically resected hippocampi (n = 9) and comparison tissue from autopsies (n = 3) were studied for: 1. Granule cell mRNA levels using in situ hybridization for brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3); 2.

Immunochemical extraction and automated measurement of plasma creatine kinase MB isoenzyme and creatine kinase MB2 isoform.

Measurement of creatine kinase MB (CK-MB) and its isoforms CK-MB2 and CK-MB1 are now applied in the diagnosis of acute myocardial infarction (AMI). The most common approach for analysis includes RIA, IRMA, and electrophoresis, all of which may be time-consuming. This study examines determination of CK-MB and CK-MB2 by a rapid immunochemical extraction method followed by an automated measurement for both analytes.

Surface antigens of the syphilis spirochete and their potential as virulence determinants.

A unique physical feature of Treponema pallidum, the venereally transmitted agent of human syphilis, is that its outer membrane contains 100-fold less membrane-spanning protein than the outer membranes of typical gram-negative bacteria, a property that has been related to the chronicity of syphilitic infection. These membrane-spanning T. pallidum rare outer membrane proteins, termed TROMPs, represent potential surface-exposed virulence determinants and targets of host immunity.

Primum atrial septal defect.

Unlabelled: The purpose of this report is to review our surgical experience with primum atrial septal defect. Since 1982, infants with primum atrial septal defect have undergone complete repair consisting of closure of the cleft of the left atrioventricular valve and atrial septal defect with a pericardial patch. Ages at operation ranged from early neonatal period until 5 years.

Antimicrobial peptides of leukocytes.

Leukocytes use an array of antimicrobial peptides and proteins to help them destroy invading microorganisms. These endogenous antibiotic molecules are remarkable for their structural variety, rapid evolutionary divergence, intraspecies variation, and complex yet subtle interactions with their targets. This arsenal has been studied most extensively in neutrophils, where its members include lactoferrin, secretory phospholipase A2, lysozyme, and the cathelicidins in the secretory granule compartment; defensins, bactericidal permeability inducing protein, serprocidins, and (again) lysozyme in the azurophil granule compartment; and calprotectin in the cytosolic compartment.

Regulation of Na+/glucose cotransporters.

Na+/glucose cotransporters (SGLTs) are expressed in the small intestine and the proximal renal tubule, where they play a central role in the absorption of glucose and galactose from food and the reabsorption of glucose from the glomerular filtrate. The regulation of intestinal sugar absorption occurs over two distinct time scales, one over days and the other over minutes. This review focuses on the mechanisms involved in the shorter-term regulation.

Tuberculosis skin testing among homeless adults.

Objective: To document the prevalence of tuberculosis (TB) skin test positivity among homeless adults in Los Angeles and determine whether certain characteristics of homelessness were risk factors for TB.

Design: Cross-sectional study.

Setting: Shelters, soup lines, and outdoor locations in the Skid Row and Westside areas of Los Angeles.

Maturation of receptor proteins in eukaryotic expression systems.

Transient and stable expression in eukaryotic cells is commonly used to examine receptor function. Characterization of the V2 vasopressin receptor synthesized in transiently transfected cells revealed the presence of large quantities of immature protein and a small fraction of fully mature protein. The immature protein was characterized by its sensitivity to endoglycosidase H treatment, abnormal migration in SDS PAGE, and a tendency to form aggregates.

Acute effects of intravenous cocaine on pulmonary artery pressure and cardiac index in habitual crack smokers.

Background: Some habitual crack cocaine smokers who deny IV drug abuse show decreased pulmonary transfer of carbon monoxide (DCO). We speculated that repeated elevations in pulmonary artery pressure (PAP) might cause pulmonary capillary damage and result in a lowered DCO, or that the reduction could be due to anoxic lung injury secondary to repeated episodes of cocaine-induced pulmonary vascular constriction.

Study Objective: Compare the acute effects of i.

Modulation of renal cortical blood flow during static exercise in humans.

During static exercise, several reflex systems that increase sympathetic nerve activity, heart rate, arterial pressure, and cardiac output are activated. At rest, the renal circulation receives the most blood flow per tissue weight of any organ in the body. However, the renal circulatory response to static exercise has not been studied in humans because of technical limitations in methods for measuring rapid changes in renal blood flow.

Effects of dobutamine stimulation on myocardial blood flow, glucose metabolism, and wall motion in normal and dysfunctional myocardium.

Background: This investigation examines the effects of inotropic stimulation on myocardial blood flow (MBF) and glucose metabolism (MRGlc) in dysfunctional myocardium through the use of positron emission tomography (PET).

Methods And Results: Nineteen patients with chronic coronary artery disease and 12 normal volunteers were studied with 13N-ammonia, 18F-deoxyglucose, and PET and with two-dimensional echocardiography at baseline and during intravenous dobutamine (5 to 10 micrograms/kg per minute). At rest, MBF in mismatch regions (n = 10) averaged 0.

Modeling for intergroup comparisons of imaging data.

Intergroup comparisons pose unique challenges in the analysis of functional imaging data. Imperfections in intersubject stereotaxis can give rise to artifactual results and make it particularly important to allow for intersubject differences in task-related changes when formulating statistical models. Because intergroup comparisons generally involve inferences about the populations from which the subjects were drawn rather than inferences about the particular subjects themselves, subjects must be treated as random rather than fixed effects in the statistical model.

Signal transduction-based strategies for the treatment of chronic myelogenous leukemia.

Recent studies of the BCR-ABL fusion protein, the product of the oncogene responsible for chronic myelogenous leukemia, have identified a number of signal transduction pathways that are activated by this tyrosine kinase. In some cases, these pathways are critical mediators of the growth stimulatory effects of the oncogene on hemopoietic cells. This knowledge has been translated into therapeutic strategies that directly target BCR-ABL or the signaling pathways that BCR-ABL activates.

Inhibition of glyceraldehyde-3-phosphate dehydrogenase in post-ischaemic myocardium.

Objective: Myocardial reperfusion following brief period of ischaemic is associated with prolonged, reversible periods of metabolic dysfunction. As the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is inhibited in vitro by reactive oxygen species, we hypothesized that production of reactive oxygen species during reperfusion would lead to inhibition of GAPDH in post-ischaemic myocardium.

Methods: Anaesthetized closed-chest-dogs were subjected to 20 min balloon occlusion of the left anterior descending coronary artery.

The sequence NPFXD defines a new class of endocytosis signal in Saccharomyces cerevisiae.

The yeast membrane protein Kex2p uses a tyrosine-containing motif within the cytoplasmic domain for localization to a late Golgi compartment. Because Golgi membrane proteins mislocalized to the plasma membrane in yeast can undergo endocytosis, we examined whether the Golgi localization sequence or other sequences in the Kex2p cytoplasmic domain mediate endocytosis. To assess endocytic function, the Kex2p cytoplasmic domain was fused to an endocytosis-defective form of the alpha-factor receptor.

Continuous arterial gas monitoring: initial experience with the Paratrend 7 in children.

Objective: To describe clinical usage of the Paratrend 7 continuous arterial blood gas monitor in children.

Design: Children older than 24 months of age who required significant ventilatory intervention were eligible for sensor placement.

Interventions: The sensor was placed via the arterial catheter to measure pH, PCO2, PO2, and temperature.

Comparative analysis of the virulence control systems of Bordetella pertussis and Bordetella bronchiseptica.

Bordetella pertussis and Bordetella bronchiseptica contain nearly identical BvgAS signal-transduction systems that mediate a biphasic transition between virulent (Bvg+) and avirulent (Bvg-) phases. In the Bvg+ phase, the two species express a similar set of adhesins and toxins, and in both organisms the transition to the Bvg- phase occurs in response to the same environmental signals (low temperature or the presence of nicotinic acid or sulphate anion). These two species differ, however, with regard to Bvg(-)-phase phenotypes, host specificity, the severity and course of the diseases they cause, and also potentially in their routes of transmission.