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Biomedical subjects

A Peterson

Publications and source records attributed to A Peterson.

At least 55 records · Page 3Linked to original sources

Myelination in the absence of myelin-associated glycoprotein.

The hypothesis that myelin-associated glycoprotein (MAG) initiates myelin formation is based in part on observations that MAG has an adhesive role in interactions between oligodendrocytes and neurons. Furthermore, the over- or underexpression of MAG in transfected Schwann cells in vitro leads to accelerated myelination or hypomyelination, respectively. Here we test this idea by creating a null mutation in the mag locus and deriving mice that are totally deficient in MAG expression at the RNA and protein level. In adult mutant animals the degree of myelination and its compaction are normal, whereas the organization of the periaxonal region is partially impaired. Mutant animals show a subtle intention tremor. Our findings do not support the widely held view that MAG is critical for myelin formation but rather indicate that MAG is necessary for maintenance of the cytoplasmic collar and periaxonal space of myelinated fibres.

Animals↗

Neurofilament-deficient axons and perikaryal aggregates in viable transgenic mice expressing a neurofilament-beta-galactosidase fusion protein.

Interactions between neurofilament side arms may modulate axon caliber. To investigate this hypothesis, we derived transgenic mice expressing a fusion protein in which the carboxyl terminus of the high molecular weight neurofilament protein (NFH) was replaced by beta-galactosidase. The transgene, regulated by NFH sequences, was expressed in projection neurons. However, the fusion protein remained in perikarya precipitating large filamentous aggregates. Axons were not invested with neurofilaments and developed only small calibers. Perikaryal aggregates, with similar structural features, are associated with neurodegenerative diseases, but these mice showed few ill effects and their neurons rarely degenerated. We conclude that an organized neurofilament cytoskeleton is required by axons to achieve large calibers but is not essential for neuronal function or extended survival.

Animals↗

A transcript map of the Down syndrome critical region on chromosome 21.

A catalogue of the genes encoded by chromosome 21 would provide a framework for assigning roles in the etiology of Down syndrome (DS) to individual genes. We have begun generating such a catalogue, starting with a 1.2 Mb region surrounding the marker D21S55. Our efforts utilized the yeast artificial chromosome (YAC) and cosmid-clone based high resolution physical maps that we have constructed of this region. Direct-selection of fetal brain cDNAs with YAC DNA was used to isolate transcribed sequences. The selected cDNA fragments were analyzed by limited DNA sequence analysis, Northern blot hybridization and screening of cDNA libraries. The cDNA fragments were assigned positions on the physical map by hybridization to a collection of cosmid clones. The accurate determination of map positions for individual cDNA fragments allowed us to determine sources of variability in the cDNA selection procedure. The combined analysis and mapping was used to estimate the completeness of our mapping efforts and to identify procedures that would facilitate large-scale transcript mapping. The transcribed sequence map that we have assembled will allow the importance to DS of genes in this region to be examined and will aid in the design of strategies for larger scale efforts.

Base Sequence↗

A high resolution physical map of 2.5 Mbp of the Down syndrome region on chromosome 21.

The region surrounding D21S55 in band 21q22 of human chromosome 21 has been implicated in the etiology of Down syndrome (DS). In this paper, we report the construction of a high resolution map of a 2.5 Mb region around the marker D21S55. Characterization of YAC clones by accurate size determination, end isolation and marker assignment was used to build a refined YAC-based map. The YAC clones were then used to isolate 284 cosmid clones, covering 2.3 Mb, from a chromosome 21-specific cosmid library. The cosmid clones were ordered into overlapping groups and a restriction map of each group was determined. The groups of cosmids were then ordered and oriented with respect to the YAC-based map. This high resolution map provides the framework for further analysis of the region by transcribed sequence mapping and sequence determination.

Base Composition↗

Staged diabetes management. Toward an integrated model of diabetes care.

This paper introduces a new and innovative approach to diabetes management in the primary-care setting. Staged diabetes management (SDM) represents a four-year effort to develop and test a data-based approach to diabetes management that could be easily adapted to a variety of health-care settings in which diabetes management is principally under the direction of primary-care physicians was limited access to specialists. After testing under controlled circumstances at the International Diabetes Center (Minneapolis, MN), SDM was subjected to substantial field trials under conditions that represent the scope and variety of primary-care practices in diabetes. The following represents the work of several investigators who independently undertook a review of SDM.

Databases, Factual↗

The Mayo Clinic experience with the cochlear implant.

The implantation of a cochlear electronic prosthetic device is an acceptable means of improving the communication ability of pre- and postlingually deafened children and adults. A significant number of patients in this series are in the senior citizen age group. It has been beneficial in improving communication ability in selected profoundly deafened individuals. There has been a significant improvement in the cochlear electronic prosthetic device since the initial report of Djourno in 1957.

Adult↗

The effects of tumour necrosis factor alpha on the vascular bed and blood flow in an experimental rat hepatoma.

The influence of TNF alpha on tumour growth rate has been attributed to its effects on the vascular bed and blood flow. The aim of our study was to investigate the effects of pharmacological doses of TNF alpha on the tumour vascular bed and to quantify blood flow in an experimental hepatoma during a more extended period after TNF-alpha exposure than hitherto reported. In Lister rats, a syngeneic rat hepatoma was implanted on the dorsum of the right hind foot. TNF alpha was given i.v. The injection was repeated after 24 hr. Tumour blood flow was estimated before and 1, 24, and 96 hr after TNF-alpha administration with the 133Xe-washout technique. The passage of microspheres through the tumour vascular bed (non-entrapment), as a measure of vascular occlusion, was estimated 4 and 96 hr after TNF-alpha administration. Tumour growth rate was measured. The tumours were subjected to histological examination and the sensitivity to TNF alpha in vitro was tested. A reduction of tumour blood flow was observed in TNF-alpha-treated groups. Tumour growth rate was equally increased after 96 hr in both the TNF-alpha groups as compared with controls. There was no significant change in non-entrapment for the TNF-alpha-treated rats as compared with controls. Histology revealed extensive necrosis and thrombosis in tumours. TNF alpha had no effect on the viability of the cloned hepatoma cell line in vitro.

Animals↗

Genome mapping by arbitrary amplification of yeast artificial chromosomes.

Several methods have been described for using the polymerase chain reaction (PCR) to isolate fragments of DNA for genome mapping. We have developed an approach for isolating discrete fragments by amplifying DNA with single oligonucleotides (10-mers) with arbitrarily selected sequences. The method is rapid and technically simple. We isolated fragments from a contig of three yeast artificial chromosomes (YACs) from the human Xq28 chromosomal region. We purified YACs yWXD37, yWXD348, and yWXD705 from a preparative pulsed field gel. Amplifications of each YAC were performed with single 10-mers as the PCR primers and the products were visualized on agarose gels. These fragments have been successfully used as hybridization probes against Southern blots containing the YACs and against blots containing human genomic DNA and somatic cell hybrids containing Xq28 as their only human constituent. The results have been concordant with the known order of the YACs. We have also successfully combined 10-mers with primers derived from vector arm sequences to isolate YAC ends. We discuss several uses of this method in comparative mapping and in filling in gaps in physical and genetic maps.

Base Sequence↗

Preparation and in vitro evaluation of "no-carrier-added" 18F-labeled biotin.

This paper will describe the preparation of "no-carrier-added" 18F-labeled biotin where the radiolabel bound to an aromatic moiety is described. This has been accomplished by preparation of [18F]fluorobenzylbromide (yield 20-30%) and its reaction with biotin-LC-hydrazide. This yielded "no-carrier-added" radiolabeled biotin (5-10%) which was then purified by reversed phase HPLC. The pure product was found to bind to avidin, thereby demonstrating retention of its biological integrity. Thus this product is potentially useful for imaging tumor tissue following injection of avidin coupled MoAbs.

Avidin↗

Preparation and preliminary biological evaluation of [18F]NCQ-115: a new selective reversible dopamine D2 receptor ligand.

18F-labeled dopamine D2 antagonist, NCQ-115 ((+)-(R)-5-bromo-N-((1-(fluorobenzyl)-2-pyrrolidinyl)-methyl-2,3- dimethoxybenzamide), was successfully prepared using a remotely controlled system. [18F]Fluoride was reacted with the trifluoromethanesulfonate salt of 4-(trimethylamino)benzaldehyde. The product was first reduced with LAH, and then reacted with thionyl bromide to yield 18F-labeled 4-fluorobenzylbromide. [18F]4-Fluorobenzylbromide was then reacted with the pyrrolidie precursor (NCQ-282) to yield the product [18F]NCQ-115 contaminated with unreacted starting material. The product was purified by reverse phase chromatography yielding [18F]NCQ-115 with a specific activity of more than 1400 Ci/mmol. Autoradiographic and biodistribution data following injection of [18F]NCQ-115 in rats revealed the regional uptake of striatum/cerebellum to be 3.2 at 30 min post-injection.

Animals↗

Diminished support for linkage between manic depressive illness and X-chromosome markers in three Israeli pedigrees.

The hypothesis that chromosomal region Xq27-28 harbours a gene for manic-depression has been a focus of interest in human genetics. X-linked inheritance of manic depressive illness has been re-examined in 3 multigeneration Israeli kindreds. Extension and re-evaluation of pedigree data, including new individuals, diagnostic follow-up, and analysis with DNA markers, shows greatly diminished support for linkage to Xq28. The peak lod scores in two of the pedigrees have dropped several lod units to clearly negative values at the RCP-F8-G6PD gene cluster. On the other hand, positive lod scores (Zmax = 2.09) are sustained in another pedigree at the same map location. None of the pedigrees show linkage to more proximal markers, including the Xq27 locus DXS98. Our analysis underscores the uncertainties in studying complex disorders.

Adult↗

Competency-based orientation in pediatric critical care.

Having recognized the need to update and modify their orientation program, a PICU nursing management team decided to develop a competency-based program. The goal was to facilitate transition of an orientee into a competent entry-level practitioner. This article outlines the procedure used to develop the initial phases: lists of competencies, competency evaluation worksheet and performance checklists. Later, various learning options and additional evaluation methods will be explored.

Child↗

Glucose intolerance as a consequence of oral terbutaline treatment for preterm labor.

BACKGROUND: In this case series, glucose regulation is examined prospectively during treatment with terbutaline sulfate for premature labor in women who were (1) previously documented as nondiabetic, (2) found to have gestational diabetes mellitus (GDM), and (3) tested for glucose intolerance while terbutaline was being administered. The glucose profiles of women treated with terbutaline were contrasted with the profiles of nondiabetic women and women known to have GDM who were not in premature labor. METHODS: Subjects tested capillary blood glucose an average of five times a day during terbutaline treatment and for 1 week after terbutaline treatment was discontinued. They used memory-based reflectometers that stored and transmitted self-monitored blood glucose data to a personal computer. RESULTS: A significant difference (P = .001) was found between average fasting glucose values (111 +/- 23 mg/dL) for the five nondiabetic subjects treated with terbutaline and values of patients in an historical control group (41 nondiabetic pregnancies [72 +/- 22 mg/dL]) who were not in premature labor. The four diabetic subjects and the one subject who had not been previously tested also experienced higher blood glucose levels during tocolytic therapy. Glucose levels returned to preintervention values with the cessation of terbutaline therapy. CONCLUSIONS: It has been previously suggested that terbutaline increases hepatic glycogenolysis, which may aggravate glucose intolerance. This phenomenon, combined with normal pregnancy-induced insulin resistance, may explain abnormal ambulatory glucose patterns in women who are euglycemic before introduction of terbutaline therapy.

Adult↗

Phosphoinositide-specific phospholipase C-delta 1 binds with high affinity to phospholipid vesicles containing phosphatidylinositol 4,5-bisphosphate.

We studied the binding of phosphoinositide-specific phospholipase C-delta 1 (PLC-delta) to vesicles containing the negatively charged phospholipids phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylserine (PS). PLC-delta did not bind significantly to large unilamellar vesicles formed from the zwitterionic lipid phosphatidylcholine (PC) but bound strongly to vesicles formed from mixtures of PC and PIP2. The apparent association constant for the putative 1:1 complex formed between PLC-delta and PIP2 was Ka congruent to 10(5) M-1. The binding strength increased further (Ka congruent to 10(6) M-1) when the vesicles also contained 30% PS. High-affinity binding of PLC-delta to PIP2 did not require Ca2+. PLC-delta bound only weakly to vesicles formed from mixtures of PC and either PS or phosphatidylinositol (PI); binding increased as the mole fraction of acidic lipid in the vesicles increased. We also studied the membrane binding of a small basic peptide that corresponds to a conserved region of PLC. Like PLC-delta, the peptide bound weakly to vesicles containing monovalent negatively charged lipids; unlike PLC-delta, it did not bind strongly to vesicles containing PIP2. Our data suggest that a significant fraction of the PLC-delta in a cell could be bound to PIP2 on the cytoplasmic surface of the plasma membrane.

Amino Acid Sequence↗