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Biomedical subjects

L Anderson

Publications and source records attributed to L Anderson.

At least 217 records · Page 12Linked to original sources
PubMed1991

APP717, APP693, and PRIP gene mutations are rare in Alzheimer disease.

The amyloid precursor protein (APP) gene codes for the precursor to the beta-protein found in the amyloid deposits of Alzheimer disease (AD). Recently Goate et al. identified in codon 717 of this gene a missense mutation which segregates with AD in a familial AD (FAD) kindred. The same mutation was also found in affected subjects from a second FAD family but not in other FAD families or in normal controls. The following work was undertaken to determine the frequency of the codon 717 mutation in FAD and nonfamilial AD cases and in normal controls. We tested 76 FAD families, 127 "sporadic" AD subjects, 16 Down syndrome cases, and 256 normal controls for this mutation, and none were positive. We also tested for the APP codon 693 mutation associated with hereditary cerebral hemorrhage with amyloidosis-Dutch type, for PRIP gene missense mutations at codons 102, 117, and 200, and for the PRIP insertion mutations which are associated with Creutzfeld-Jakob disease and Gerstmann-Straussler Scheinker syndrome. No examples of these mutations were found in our population. Thus these APP and PRIP mutations are rare in both FAD and nonfamilial AD.

Adult↗
PubMed1991

Methotrexate in rheumatoid arthritis: effects on disease activity in a multicenter prospective study.

One hundred and twenty-three patients with rheumatoid arthritis (RA) who successfully completed a randomized trial comparing oral methotrexate (MTX) to auranofin enrolled in a longterm prospective study of oral MTX. Of the 91 patients who completed 24 months of therapy, a significant (p = 0.0001) improvement was noted compared to baseline in all clinical disease variables and the Westergren erythrocyte sedimentation rate (ESR). Marked improvement occurred in 94 (76%) and 98 (80%) of the patients in the joint pain/tenderness index and joint swelling index at the last evaluable visit (mean 26 months). Of the 77 patients with an elevated ESR at baseline, 29 (38%) patients normalized it (less than 20 mm/h) while receiving therapy (p less than 0.01). A significant reduction in prednisone dose was also seen. Adverse events occurred frequently but were generally mild in severity. Twenty-seven patients (22%) withdrew during the study. Four (3%) withdrew due to lack of efficacy, and 6 (5%) because of adverse experiences. The overall probability of continuing therapy in the study for 48 months was projected at 72%. This large prospective study supports the observation of earlier smaller studies that MTX is an effective drug in the treatment of RA.

Administration, Oral↗
PubMed1991

Current status of whole-body counting as a means to detect and quantify previous exposures to radioactive materials. Whole-body Counting Working Group.

This report discusses the principles, techniques, and application of whole-body counting with respect to previous radiation exposure. Whole-body counting facilities are located nationwide and have a wide range of capabilities. A listing of these facilities is provided in Appendix A. However, only a few facilities are truly state-of-the-art and have the sophisticated capabilities required to attempt detection of low-level activity in vivo. Measurements made many years after exposure can be extremely difficult to interpret. The precision and accuracy of resulting dose estimates are functions of such factors as the assumptions made concerning intake, time since intake, radionuclide metabolism, and level of intake. The indiscriminate application of metabolic models to current body contents or minimum detectable amounts of radionuclides with relatively short effective half-lives (such as 137Cs) can lead to absurd results when used as a basis for calculating intakes 25 and 40 y ago. Skull counting for 90Sr-90Y and 239,240Pu can set upper limits on possible uptakes and radiation doses, but in the case of 239,240Pu, the limits are rather high. In both cases, the accuracy of the limits depends on the metabolic models used in the calculations. These models (ICRP 1979) were developed to set safety standards for the intakes of radionuclides by workers and are not intended to be used to back-calculate uptakes and radiation doses from measurements made long after the uptake. There are, therefore, large uncertainties in any conclusions derived from these calculations. The experience gained over the years with whole- and partial-body counting has consistently shown that they are of little use in determining body contents of radionuclides resulting from exposure to weapons debris decades earlier. The development of new detectors such as an array of lithium-drifted silicon devices offers some hope of lowering the minimum detectable amount (MDA) for Pu and Am, but such detectors are still several years from routine application and do not represent current state-of-the-art. Furthermore, it is doubtful that such improvements will be sufficient to meet the need of assessing radiation exposures that occurred decades earlier.

Accidents↗
PubMed1991

To arms, to arms.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Linkage analysis of familial Alzheimer disease, using chromosome 21 markers.

Chromosome 21 markers were tested for linkage to familial Alzheimer disease (FAD) in 48 kindreds. These families had multiple cases of Alzheimer disease (AD) in 2 or more generations with family age-at-onset means (M) ranging from 41 to 83 years. Included in this group are seven Volga German families which are thought to be genetically homogeneous with respect to FAD. Autopsy documentation of AD was available for 32 families. Linkage to the 21 q11-q21 region was tested using D21S16, D21S13, D21S110, D21S1/S11, and the APP gene as genetic markers. When linkage results for all the families were summed, the LOD scores for these markers were consistently negative and the entire region was formally excluded. Linkage results were also summed for the following family groups; late-onset (M greater than 60), early-onset (M less than or equal to 60), Volga Germans (M = 56), and early-onset non-Volga Germans (M less than or equal to 60). For the first three groups, LOD scores were negative for this region. For the early-onset non-Volga German group (six families), small positive LOD scores of Zmax = 0.78 (recombination fraction theta = .15), Zmax = 0.27 (theta = .15), and Zmax = 0.64 (theta = .0), were observed for D21S13, D21S16, and D21S110, respectively. The remainder of the long arm of chromosome 21 was tested for linkage to FAD using seven markers spanning the q22 region. Results for these markers were also predominantly negative. Thus it is highly unlikely that a chromosome 21 gene is responsible for late-onset FAD and at least some forms of early-onset FAD represented by the Volga German kindreds.

Adult↗
PubMed1990

1,3,4,6-Tetra-O-acetyl-2-chloroacetamido-2-deoxy-beta-D-glucopyranose as a glycosyl donor in syntheses of oligosaccharides.

1,3,4,6-Tetra-O-acetyl-2-chloroacetamido-2-deoxy-beta-D-glucopyran ose was tested as a glycosyl donor for oligosaccharide synthesis via a ferric chloride-catalyzed coupling reaction. Glycosyl acceptors tried (6 in all) were O-benzyl-protected D-galactosides having free OH groups at positions 3 and 4, respectively, and similarly protected glycosides of D-glucose and 2-acetamido-2-deoxy-D-glucose unsubstituted on O-4. Existing syntheses of all the acceptors were improved, in four instances by exploitation of Garegg and Hultberg's cyanoborohydride procedure for the conversion 4,6-O-benzylidene----6- O-benzyl [Carbohydr. Res., 93 (1981) c10-c11; 108 (1982) 97-101]. Good to excellent yields of beta-linked disaccharides were obtained from the galactoside and glucoside acceptors, but with allyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-alpha-D-glucopyranoside, stereoselectivity was lost (alpha:beta-ratio 1:2). Allyl and benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-beta-D-glucopyranosides gave, respectively, the allyl and benzyl beta-glycosides of the donor as major products. A mechanism is proposed for this transglycosidation reaction. The N-chloroacetyl groups in the disaccharide products were readily converted into N-acetyl by reduction with zinc-acetic acid.

Carbohydrate Sequence↗
PubMed1990

Low-dose methotrexate compared with auranofin in adult rheumatoid arthritis. A thirty-six-week, double-blind trial.

Weekly treatment with low-dose oral methotrexate (MTX) was compared with daily auranofin (AUR) treatment in a 36-week double-blind, randomized, multicenter study of 281 patients with active, adult-onset rheumatoid arthritis. Both treatment groups showed significant improvement by the usual measures of clinical efficacy. The response with MTX occurred earlier and was consistently greater than that with AUR. An intent-to-treat analysis showed significantly greater improvement (P less than 0.01) with MTX for painful and swollen joint counts and physician and patient global assessments of disease activity. Adverse reactions were reported more frequently in the AUR group, and more AUR-treated patients were withdrawn from the study because of toxicity. MTX was thus more effective and better tolerated than AUR in this study.

Administration, Oral↗
PubMed1990

Inhibition by indomethacin of the increased facility of outflow induced by adrenaline.

Topical adrenaline lowers intraocular pressure (IOP) in the rabbit largely due to an increase in facility of outflow of aqueous humour. This paper studies the inhibition by indomethacin or piroxicam of the adrenaline-induced rise in facility of outflow. Topical indomethacin is shown to reduce the acute IOP changes induced by adrenaline in conscious rabbits; both the early rise and the prolonged fall in pressure were inhibited. In anaesthetized rabbits, indomethacin pretreatment prevented the large rise in facility of outflow which normally follows topical adrenaline. Indomethacin did not block the mydriasis induced by adrenaline, nor did it significantly alter aqueous humour protein levels. Piroxicam, a cyclo-oxygenase inhibitor which, unlike indomethacin, does not block Ca2+ movements in some tissues, also blocked the adrenaline-induced rise in facility of outflow, suggesting that this increased facility depends on cyclo-oxygenase and not on Ca2+ movements. Verapamil, a drug which blocks Ca2+ channels, was shown to inhibit the brief ocular hypertensive effect of adrenaline in the conscious rabbit, but to leave the hypotensive phase unchanged. It is concluded that the hypotensive mechanism of adrenaline may depend on synthesis of a prostaglandin, since inhibition of the adrenaline-induced rise in facility is achieved by inhibitors of cyclooxygenase. Despite previous reports that a prostaglandin may be responsible for the brief hypertensive phase, the present evidence suggests that Ca2+ movements may be involved, perhaps in activation of the extraocular muscles.

Animals↗
PubMed1990

Mechanics of breathing during strenuous exercise in Thoroughbred horses.

The changes induced by exercise on the mechanics of breathing, as well as the simultaneous changes occurring in arterial blood gas tensions and in respiratory gas exchange were investigated in 6 healthy thoroughbred horses, performing a treadmill exercise of increasing intensity. Respiratory airflow and tidal volume (VT) were measured with ultrasonic flowmeters. Pleural pressure changes were measured by an oesophageal balloon catheter. Gas concentration of the expired air was analysed with a mass spectrometer; the oxygen consumption (VO2) and the carbon dioxide output (VCO2) were computed breath-by-breath. Arterial blood gas values were obtained by sampling from the carotid artery. Between rest and fast gallop VT, respiratory frequency, expired minute ventilation (VE), VO2, VCO2, total pulmonary resistance (RL), mechanical work of breathing (Wrm) and PaCO2 increased significantly while PaO2 decreased significantly. The Wrm.VO2(-1) ratio in galloping horses increased exponentially with VE. This, together with the relationship between the changes in PaO2 and in PaCO2 and the increase in the ventilatory mechanics parameters, suggests that the mechanics of breathing may be one of the factors constraining further increase in ventilation in exercising healthy horses.

Animals↗
PubMed1990

A refined linkage map for DNA markers around the pericentromeric region of chromosome 10.

A refined genetic linkage map for the pericentromeric region of human chromosome 10 has been constructed from data on 12 distinct polymorphic DNA loci as well as the locus for multiple endocrine neoplasia type 2A (MEN 2A), a dominantly inherited cancer syndrome. The map extends from D10S24 (at 10p13-p12.2) to D10S3 (at 10q21-q23) and is about 70 cM long. Overall, higher female than male recombination frequencies were observed for this region, with the most remarkable female excess in the immediate vicinity of the centromere, as previously reported. Most of the DNA markers in this map are highly informative for linkage and the majority of the interlocus intervals are no more than 6 cM apart. Thus this map should provide a fine framework for future efforts in more detailed mapping studies around the centromeric area. A set of ordered cross-overs identified in this work is a valuable resource for rapidly and accurately localizing new DNA clones isolated from the pericentromeric region.

Chromosome Mapping↗
PubMed1990

Assessment of intravenous fenoldopam mesylate in the management of severe systemic hypertension.

To evaluate the acute BP response to iv fenoldopam mesylate (FNP), 14 patients with severe hypertension (diastolic BP 120 to 170 mm Hg) were studied in an open-label trial. Initial infusion rate of FNP was 0.1 microgram/kg.min. Titration to diastolic BP goal (95 to 110 mm Hg) was followed by a constant infusion phase (greater than or equal to 6 h), a detitration phase (2 h), and a postinfusion phase. FNP reduced BP by 27/29 mm Hg (p less than .001) with no significant effect on heart rate. Maintenance of the BP effect was noted through the 6 h of constant rate infusion. Mild, transient vasodilating-associated adverse effects were noted with FNP. We conclude that FNP is an effective, well-tolerated iv antihypertensive agent for acute BP reduction in a severely hypertensive population.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗