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Biomedical subjects

L Nielsen

Publications and source records attributed to L Nielsen.

At least 91 records · Page 5Linked to original sources

Comparative stereostructure-activity studies on GABAA and GABAB receptor sites and GABA uptake using rat brain membrane preparations.

The affinities of a number of analogues of gamma-aminobutyric acid (GABA) for GABAA and GABAB receptor sites and GABA uptake were studied using rat brain membrane preparations. Studies on the (S)-(+)- and (R)-(-)-isomers of baclofen, 3-hydroxy-4-aminobutyric acid (3-OH-GABA), and 4,5-dihydromuscimol (DHM) revealed different stereoselectivities of these synaptic mechanisms in vitro. Although (S)-3-OH-GABA and, in particular, (S)-DHM were more potent than the corresponding (R)-isomers as inhibitors of GABAA binding, the opposite stereoselectivity was demonstrated for the GABAB binding sites. Thus, (R)-3-OH-GABA and (R)-baclofen were more potent than the (S)-isomers as inhibitors of GABAB binding, (R)-baclofen being some five times more potent than (R)-3-OH-GABA. These two (R)-isomers actually have opposite orientation of the substituents on the GABA backbones, suggesting that the lipophilic substituent of (R)-baclofen interacts with a structural element of the GABAB receptor site different from that that binds the very polar hydroxy group of (R)-3-OH-GABA. The O-methylated analogue of 3-OH-GABA, 3-methoxy-4-aminobutyric acid (3-OCH3-GABA), did not interact significantly with GABAB sites. The homologues of GABA, trans-4-aminocrotonic acid (trans-ACA), muscimol, and 3-OH-GABA, that is, 5-aminovaleric acid (DAVA), trans-5-aminopent-2-enoic acid, homomuscimol, and 3-hydroxy-5-aminovaleric acid (3-OH-DAVA), respectively, were generally much weaker than the parent compounds, whereas 2-hydroxy-5-aminovaleric acid (2-OH-DAVA) showed a significantly higher affinity for GABAB sites than the corresponding GABA analogue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

cDNA cloning of human plasminogen activator-inhibitor from endothelial cells.

Full-length cDNA for plasminogen activator inhibitor (PAI-1) was isolated from a human umbilical vein endothelial cell (HUVEC) lambda gt11 cDNA library. Three overlapping clones were identified by immunologic screening of 10(6) recombinant phage using a rabbit anti-human fibrosarcoma PAI-1 antiserum. The fusion proteins encoded by these three clones also react strongly with a monoclonal mouse anti-human fibrosarcoma PAI-1 antibody. By nucleotide sequence analysis, PAI-1 cDNA encodes a protein containing 402 amino acids with a predicted, nonglycosylated molecular mass of 45 kD. Identity of this material as authentic PAI-1 was confirmed by the presence of high level homology with the primary amino acid sequence of an internal peptide prepared from purified rat hepatoma PAI-1. The predicted amino acid sequence also reveals extensive homology with other members of the serine protease inhibitor gene family. Cultured HUVECs contain two PAI-1 mRNA species, both encoded by a single gene, differing by 1 kb in the 3' untranslated region. The PAI-1 gene is located on human chromosome 7.

Amino Acid Sequence↗

Leiomyomatosis of the colon and mesentery: report of a case.

A case of leiomyomatosis of the colon and mesentery in a 35-yr-old man with several noninvalidating congenital malformations and multiple intracranial meningiomas is presented. The leiomyomatosis had been asymptomatic until 2 months before death, even though the lesions suggest a congenital disorder affecting the musculature of the bowel wall.

Adult↗

GABA agonists. Resolution, absolute stereochemistry, and enantioselectivity of (S)-(+)- and (R)-(-)-dihydromuscimol.

(RS)-5-(Aminomethyl)-2-isoxazolin-3-ol (dihydromuscimol, DHM) is a potent 4-aminobutyric acid (GABA) agonist, the inhibitory effects of which on neurons are sensitive to the antagonist bicuculline methochloride (BMC), and it also interacts with the GABA uptake system in vitro. (S)-(+)-DHM (4) and (R)-(-)-DHM (5) were obtained in optically pure forms via resolution of tert-butyloxycarbonyl-protected DHM (1) using cinchonidine as the only resolving agent. The optical purity and absolute stereochemistry of 4 and 5 were established by chemical correlation to the (S)-(+) enantiomer of 3-hydroxy-4-aminobutyric acid (GABOB). While 4 was a specific and potent BMC-sensitive GABA agonist in vivo and in vitro, possibly the most potent GABA agonist so far described, the inhibition of GABA uptake by DHM proved to reside exclusively in the (R)-(-) enantiomer (5). The affinity of 5 for BMC-sensitive GABA receptor sites in vitro was some 50 times lower than that of 4. Compounds 4 and 5 can be considered semirigid isosteres of the conformationally flexible GABA analogues (S)-(+)- and (R)-(-)-GABOB, respectively, which show a very low degree of enantioselectivity with respect to GABA synaptic mechanisms. This correlation between the degree of enantioselectivity and conformational mobility of chiral GABA analogues might be of importance for the design of new drugs with specific actions at synapses at which GABA is the transmitter.

Animals↗

New techniques for stenting severely strictured or occluded ureters.

Percutaneous stenting of the severely strictured ureter is facilitated by catheterization through a rigid curved tube leading through the kidney. Alternatively, bidirectional traction tensioning of a guide wire pulled through the entire urinary tract permits antegrade dilatation and stent drainage. Complete occlusion near the ureteric orifice may be bypassed by transureteral puncture of the bladder followed by stent insertion.

Aged↗

Evaluation of two methods of scoring denture plaque.

In a previously published study on the effect of an alcalase on development of denture plaque, two different methods were used to quantify plaque on the fitting surface of maxillary dentures. Both methods were based on scoring of photographs at X 10 magnification. In one of the methods the percentage area was estimated with 10% intervals from 0% to 100%. By the other method dentures were ranked according to cleanliness based on area and on degree of staining of plaque. The number of dentures in each of the 14 treatment periods was 14 or 15. The present study was conducted to determine the reliability of the two methods. Reliability of the two methods was determined by using Pearson's correlation coefficient and Kendall's tau. Both intra- and inter-examiner reliability was high. A high correlation between the two methods was also demonstrated.

Dental Health Surveys↗

Colorectal bleeding localized with gamma camera.

Localization of colorectal bleeding using a gamma camera was attempted in a prospective study of 24 patients after in-vivo labelling of their erythrocytes with 99mTc-pertechnetate. In 7 of 8 patients with bright-red rectal bleeding a correct localization was given by scintiphotos, thus helping the surgeon to plan the operative procedure. Of 11 patients with recently acute colorectal bleeding but no signs of actual haemorrhage, 8 had no scintigraphic bleeding. Five investigations had to be excluded due to technical errors. The scintigraphic classification was correct in a significant number of patients (p less than 0.02). It is concluded that bleeding can be identified in colorectum at brisk-haemorrhagic stools and be correctly localized to the right or left side of the colon. This non-invasive scintigraphic procedure should therefore be undertaken before an abdominal 2-3 vessel arteriography is performed.

Colonic Diseases↗

Comparison of six assays for glycosylated haemoglobin determination.

To examine which glycosylated haemoglobin A components and which assays are the most useful in assessing long-term control in diabetic patients we have compared glycosylated haemoglobin concentrations in normal subjects and diabetic patients measured by six different methods, three chromatographic, a colorimetric, an isoelectric focusing and an agar gel electrochromatographic method. Despite the fact that the correlation between methods was high and the precision calculated from intra-assay variations acceptable, several differences in results were found. Thus Isolab columns determined lower values than other chromatographic methods and the unstable aldimine fraction interfered in agar gel electrochromatography. The increase in HbA1 in diabetics compared with normals was less than the corresponding increase in both HbA1c and total ketoamine bound glucose. This finding was consistent with the observation that the contribution of HbA1a + b fraction to HbA1 was constant at glucose concentrations above 10 mmol/l while a linear increase in these minor haemoglobins and consequently in HbA1 occurred at glucose concentrations below this level. We conclude that HbA1c' determined either by isoelectric focusing or ion exchange chromatography are the assays of choice for the determination of glycosylated haemoglobin in clinical routine.

Calorimetry↗

Thymic mast cell deficiency in avian muscular dystrophy.

In animals with hereditary muscular dystrophy there are thymic abnormalities which may be of etiological significance in the dystrophic process. This study investigated mast cell number and histamine levels in the thymus of normal and dystrophic chickens. For comparison, other lymphoid tissues, namely the spleen and the bursa of Fabricius, and non-lymphoid tissues including the comb and pectoralis major muscle, were similarly studied. Our results show that the thymus of dystrophic adult birds has a deficiency in both mast cell number and histamine content. In the bursa of Fabricius of dystrophic birds a significant elevation in histamine content (microgram/g) was attributed to the abnormally small size of this organ, rather than to an absolute mast cell increase. The deficiency in thymic mast cell number in dystrophic chickens may be significant in the postulated abnormal thymus-muscle interaction of the dystrophic process.

Animals↗

Can postoperative pulmonary conditions be improved by treatment with the Bartlett-Edwards incentive spirometer after upper abdominal surgery?

During the immediate postoperative course after upper abdominal surgery, pulmonary complications often occur, caused, inter alia, by reduced regional ventilation and by atelectases as a result of: (1) narrowing of the small peripheral bronchi, and (2) impaired respiratory function. Based on these pathophysiological mechanisms, an instrument (Bartlett-Edwards Incentive Spirometer) has been devised, which aims at giving the patient an opportunity of sustained maximal inspiration under standardized and controlled conditions. The use of this instrument has been followed by reports of a considerable reduction in postoperative pulmonary complications. In a controlled clinical investigation of the pre- and postoperative condition of the lungs, we were unable to show any beneficial effect of the instrument. In general, we have a low frequency of severe postoperative pulmonary complications, as compared with the results reported in the literature. We ascribe this to our very effective pre- and postoperative respiratory therapy.

Abdomen↗