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Biomedical subjects

L Iversen

Publications and source records attributed to L Iversen.

108 records · Page 6Linked to original sources

Reduced cortical choline acetyltransferase activity in senile dementia of Alzheimer type is not accompanied by changes in vasoactive intestinal polypeptide.

Post-mortem brain tissue from 7 patients who died with a diagnosis of senile dementia of Alzheimer type (SDAT) was compared with tissue obtained from 7 control patients at routine post mortem. A significant fall in choline acetyltransferase (ChAT) activity was apparent in the cerebral cortex of the SDAT cases which was maximal in the temporal lobe. The fall in ChAT activity was not accompanied by changes in cortical vasoactive intestinal polypeptide (VIP) measured by radioimmunoassay.

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Benzodiazepine receptors: the effect of GABA on their characteristics in human brain and their alteration in Huntington's disease.

The characteristics of bezodiazepine (BDZ) receptors were studied in the putamen and substantia nigra (SN) of control and Huntington's disease (HD) human brains. In the putamen, there was a significant decrease in density BDZ receptors in the HD tissue. In addition the application of GABA significantly potentiated DBZ receptor binding in both the HD and control putamen. In the SN, an increase in BDZ receptor density was detected in the HD tissue. GABA enhanced [3H]flunitrazepam binding in both the HD and control SN by increasing the affinity of BDZ receptors for [3H]flunitrazepam. The results suggest that there are alterations in BDZ receptors in HD human brain and that these alterations may be related to the neuronal pathology of this disease. This study also provides evidence for a coupling of GABA receptors to BDZ receptors in human brain.

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No evidence for lateral asymmetry of neurotransmitters in post-mortem human brain.

A study of post-mortem human brain was undertaken to establish whether there is any evidence for lateral asymmetry of neurotransmitters. Choline acetyltransferase, glutamic acid decarboxylase, alpha-aminobutyric acid, dopamine and noradrenaline were measured in nine comparable areas from the left and right hemispheres of normal post-mortem human brain. Only nigral GABA showed a left-right difference at a significance level of 5%. These negative post-mortem findings suggest that chemical laterality is unlikely to be an important source of error in human post-mortem studies.

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Biomarkers for early effects of carcinogenic dual-acting PPAR agonists in rat urinary bladder urothelium in vivo.

Small-molecule agonists of the peroxisome proliferator-activated receptor (PPAR) alpha and gamma isoforms (dual-acting PPAR agonists) can cause urothelial cancers in rodents. Rats were dosed orally for 16 days with bladder carcinogenic (ragaglitazar) as well as non-bladder carcinogenic (fenofibrate and rosiglitazone) PPAR agonists and protein changes were assayed in the urinary bladder urothelium by Western blotting. Dose levels reflected 10-20 x human exposure, and the ragaglitazar dose was in the carcinogenic range. Ragaglitazar induced expression of the transcription factor Egr-1, phosphorylation of the c-Jun transcription factor and phosphorylation of the ribosomal S6 protein were observed. These changes were also observed in rats dosed with either rosiglitazone or fenofibrate. However, the protein changes were stronger (Egr-1 induction) or of a longer duration (S6 phosphorylation) in ragaglitazar-treated animals. Animals co-administered fenofibrate (a specific PPARalpha agonist) and rosiglitazone (a specific PPARgamma agonist) exhibited Egr-1 and S6 protein changes more similar to those induced by ragaglitazar (a dual-acting PPARalpha/gamma agonist) than either fenofibrate or rosiglitazone alone. The findings suggest that ragaglitazar causes Egr-1, c-Jun and S6 protein changes in the urothelium by a mechanism involving PPARalpha as well as PPARgamma, and that the Egr-1, c-Jun and S6 protein changes might have potential biomarker value.

Animals↗

Auscultation in mild mitral regurgitation in dogs: observer variation, effects of physical maneuvers, and agreement with color Doppler echocardiography and phonocardiography.

Observer variation in diagnosing mild mitral regurgitation in dogs by cardiac auscultation was assessed by having 6 veterinarians with different levels of experience examine 57 Cavalier King Charles Spaniels. Comparisons with color Doppler echocardiography and phonocardiography were made, and the effects of 2 physical maneuvers on the auscultatory findings were evaluated. Using mildly diseased dogs, interobserver agreement in diagnosing the presence or absence of left-sided murmurs ranged from 63% to 88%. The agreement with phonocardiography (range, 53-91%) increased with the amount of observer experience. The 2 most experienced observers could discern soft ejection murmurs from regurgitant murmurs and were able to diagnose 89% of the dogs with regurgitant jets larger than 30% of the left atrial area. In general, less experienced observers diagnosed most jets larger than 50%. In many dogs with small jets, no murmur was found by auscultation and phonocardiography. The audibility of mild regurgitation was significantly reduced in dogs that were difficult to auscultate. Early systolic murmurs were typical of mild regurgitation, whereas holosystolic murmurs typified severe regurgitation. In a few dogs, late systolic murmurs alternated with holosystolic murmurs. Systolic clicks were found phonocardiographically in 18 dogs with mild to moderate regurgitation, but the audibility apparently was low. In many mildly affected dogs, physical maneuvers increased murmur intensity. Thus, some form of dynamic auscultation might facilitate the diagnosis of mild regurgitation. Auscultatory findings in mild regurgitation appear to depend on observer experience, circulatory status, and how difficult the dog is to auscultate.

Animals↗