Molecular forms of acetylcholinesterase in subcortical areas of normal and Alzheimer disease brain

We have previously reported that the 10s molecular form (G4) of acetylcholinesterase (AChE) is selectively lost from several cortical areas of Alzheimer's disease (AD) brain. In the current follow-up study, we microdissected several areas of nondemented and AD brain, including the hippocampus, amygdala, and cingulate gyrus. Tissue homogenates were separated on sucrose density gradients and the resulting fractions were analyzed for AChE activity in order to define the ratios of the predominant AChE molecular forms (G4/G1). Both the hippocampus and amygdala exhibited distinct patterns of alterations in the G4/G1 ratio which correlate with the known distribution of histopathological changes in AD brain. In order to further define the major pool of AChE that is depleted in AD, we separated fractionated tissue homogenates into salt-soluble and detergent-soluble fractions. The G4/G1 ratios were only altered in the detergent-soluble fractions, indicating that the loss of the G4 AChE molecular form involves a selective depletion of the membrane pool. Available evidence would suggest that this form is the AChE molecular form physiologically relevant at the cholinergic synapse.     

Distribution of the molecular forms of acetylcholinesterase in human brain: alterations in dementia of the Alzheimer type

Acetylcholinesterase (AChE), the enzyme that degrades acetylcholine, is a heterogeneous enzyme that can be separated into multiple molecular forms. A tetrameric membrane-bound form (G4) and a monomeric soluble form (G1) are the two predominant enzyme species in mammalian brain. The distribution of AChE molecular forms was defined by sucrose density gradients of 11 anatomical regions of postmortem brains from 10 patients with dementia of the Alzheimer type (DAT) and 14 nondemented controls of similar ages. The results demonstrate an overall loss of protein and enzyme activity in all areas of the DAT brains studied and a selective loss of the G4 form of AChE in Brodmann areas 9, 10, 11, 21, 22, and 40, and the amygdala. There was no change in the G4/G1 ratio in areas 17 and 20, in the hippocampus, or in the cerebellum. There was a high regional correlation of the G4/G1 ratios with published values for choline acetyltransferase activity but lower correlation with total AChE activity. We propose that there is a predominant loss of the G4 form of AChE in DAT and that this loss is correlated with the degeneration of presynaptic elements.     

Two complementary personal medication management applications developed on a common platform: case report

Background

Adverse drug events are a major safety issue in ambulatory care. Improving medication self-management could reduce these adverse events. Researchers have developed medication applications for tethered personal health records (PHRs), but little has been reported about medication applications for interoperable PHRs.

Objective

Our objective was to develop two complementary personal health applications on a common PHR platform: one to assist children with complex health needs (MyMediHealth), and one to assist older adults in care transitions (Colorado Care Tablet).

Methods

The applications were developed using a user-centered design approach. The two applications shared a common PHR platform based on a service-oriented architecture. MyMediHealth employed Web and mobile phone user interfaces. Colorado Care Tablet employed a Web interface customized for a tablet PC.

Results

We created complementary medication management applications tailored to the needs of distinctly different user groups using common components. Challenges were addressed in multiple areas, including how to encode medication identities, how to incorporate knowledge bases for medication images and consumer health information, how to include supplementary dosing information, how to simplify user interfaces for older adults, and how to support mobile devices for children.

Conclusions

These prototypes demonstrate the utility of abstracting PHR data and services (the PHR platform) from applications that can be tailored to meet the needs of diverse patients. Based on the challenges we faced, we provide recommendations on the structure of publicly available knowledge resources and the use of mobile messaging systems for PHR applications.     

DNA sequence and comparative genomics of pAPEC-O2-R, an avian pathogenic Escherichia coli transmissible R plasmid

In this study, a 101-kb IncF plasmid from an avian pathogenic Escherichia coli (APEC) strain (APEC O2) was sequenced and analyzed, providing the first completed APEC plasmid sequence. This plasmid, pAPEC-O2-R, has functional transfer and antimicrobial resistance-encoding regions. The resistance-encoding region encodes resistance to eight groups of antimicrobial agents, including silver and other heavy metals, quaternary ammonium compounds, tetracycline, sulfonamides, aminoglycosides, trimethoprim, and beta-lactam antimicrobial agents. This region of the plasmid is unique among previously described IncF plasmids in that it possesses a class 1 integron that harbors three gene cassettes and a heavy metal resistance operon. This region spans 33 kb and is flanked by the RepFII plasmid replicon and an assortment of plasmid maintenance genes. pAPEC-O2-R also contains a 32-kb transfer region that is nearly identical to that found in the E. coli F plasmid, rendering it transferable by conjugation to plasmid-less strains of bacteria, including an APEC strain, a fecal E. coli strain from an apparently healthy bird, a Salmonella enterica serovar Typhimurium strain, and a uropathogenic E. coli strain from humans. Differences in the G+C contents of individual open reading frames suggest that various regions of pAPEC-O2-R had dissimilar origins. The presence of pAPEC-O2-R-like plasmids that encode resistance to multiple antimicrobial agents and that are readily transmissible from APEC to other bacteria suggests the possibility that such plasmids may serve as a reservoir of resistance genes for other bacteria of animal and human health significance.     

Various family problems of early education of early treated children with clefts]

To prevent retardation in personality development of physically and mentally handicapped children and adolescents, more attention should be paid to the qualification of parents, kindergarten teachers and teachers to educate handicapped children, and so those with cleft lips and palates. This is corroborated by findings obtained of 21 mothers of early-treated cleft children who had been involved in the present study. To qualify parents and co-educators to educate and care cleft children, they are needing sympathetic guidance by, and paedagogical advice from, all those who are contributing to rehabilitation.     

Determination of trazodone in serum by instrumental thin-layer chromatography

A simple and specific method for trazodone that uses high-performance thin-layer chromatography (TLC) plates for chromatography and the Camag TLC Scanner for fluorescence-reflectance measurements is described. The quantitative method employs quinidine as an internal standard and the calibration line is linear between 0.2 and 2.0 mg/L serum, the usual range encountered in patients treated with the drug. Replicate analyses of single serum specimens demonstrated reproducibility of better than +/- 3% coefficient of variation for concentrations of trazodone in the midrange of the test line.     

Choline acetyltransferase activity in omental tissue

Choline acetyltransferase (ChAT), the enzyme responsible for the formation of ACh from choline and acetyl-coenzyme A, is a marker of cholinergic function and is significantly depressed in the brains of Alzheimer patients. It has been shown that omental tissue contains several neuroactive substances and causes revascularization when placed upon the brain of stroke patients. In this study, it was demonstrated that omental tissue exhibits specific ChAT activity. This activity was choline-dependent, inhibited by N-ethylmaleimide (a known ChAT inhibitor), and was characterized by kinetic parameters consistent with values for the neuronal enzyme. It is suggested that omental placement to the brain together with oral choline administration might prove to be useful for increasing ACh synthesis in Alzheimer's disease.     

Direct serum total iron-binding capacity assay suitable for automated analyzers.

BACKGROUND: Present methods for measuring serum total iron-binding capacity (TIBC) involve manipulation of samples or performance of two assays on each sample. We developed a direct automated assay (DTIBC) for TIBC. METHODS: We added to serum a saturating amount of iron bound to an excess of chelating dye at a low pH, recorded a blank reading that represented the sum of the saturating amount of iron plus the serum iron, and then added a strong neutral pH buffer. The decrease in absorbance (as transferrin extracts iron from the iron-dye complex) is directly proportional to the TIBC. TIBC values for 125 patients were determined by DTIBC, alumina column TIBC (AC), magnetic particle TIBC (MTIBC), and the UIBC method (UIBC) on Roche COBAS FARA and Mira chemistry analyzers. In a separate study, TIBC values for 128 patients were determined on an Olympus AU400 by the DTIBC and the MTIBC methods. RESULTS: Methods comparisons on the COBAS analyzers yielded the following results: DTIBC = 1.05(MTIBC) - 1.0 micromol/L (r = 0.987; S(y/x) = 2.6 micromol/L); DTIBC = 1.07(AC) - 1.0 micromol/L (r = 0.982; S(y/x) = 3.0 micromol/L); and DTIBC = 1.14(UIBC) + 3.4 micromol/L (r = 0.982; S(y/x) = 3.0 micromol/L). A similar correlation study using the Olympus AU400 yielded DTIBC = 1.00(MTIBC) - 0.1 micromol/L (r = 0.983; S(y/x) = 2.7 micromol/L). The assay was linear from 12.5 to 125 micromol/L (70-700 microg/dL) TIBC on the COBAS FARA. Within- and between-run imprecision (CV) was 相似文献