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Biomedical subjects

T Nilsson

Publications and source records attributed to T Nilsson.

At least 253 records · Page 14Linked to original sources

Mucus secretion in hypertrophic, hypersecretory, protein-losing gastropathy.

A 48-year-old man presented with giant folds of the gastric mucosa, hypoalbuminemia, and hypersecretion of acid. In vivo labeling of plasma proteins by 51CrCl3 disclosed an abnormal gastric protein clearance. Mucus secretion, evaluated by the output of dry matter, mucosubstance constituents (hexosamine and fucose), protein (by the method of Lowry), and sodium were five to eight times those in nine healthy volunteers, but were normalized by the histamine-H2-receptor antagonist cimetidine. The proportion of dry matter and protein was the same in the patient and in healthy subjects, indicating that the loss of plasma protein into the stomach probably occurred as part of an abnormally great secretion of mucus.

Cimetidine↗

Tissue plasminogen activator concentrations in major abdominal surgery. Relationship to postoperative deep vein thrombosis.

Tissue plasminogen activator (t-PA) antigen concentrations were studied in 47 patients subjected to major abdominal surgery. The 17 patients, which developed postoperative deep vein thrombosis (DVT), diagnosed with the 125I-fibrinogen uptake test, had higher levels preoperatively, and on the sixth postoperative day, when the thrombi had already formed. The reduced fibrinolytic activity in patients with a predisposition to postoperative deep vein thrombosis is thus not related to any t-PA deficiency. The postoperative fibrinolytic shutdown may however partly be due to a drop in t-PA antigen levels, at least in the patients, which developed DVT.

Abdomen↗

Activation of platelets in the venous occlusion test.

Plasma samples were obtained from healthy subjects before and after the venous occlusion test. In the post-occlusion samples, there was a significantly increased concentration of beta-thromboglobulin and factor XII, as well as a shortening of the activated partial thromboplastin time, indicating that an activation of the coagulation system takes place during the period of venous occlusion. This finding may have implications for the laboratory evaluation of platelet function as well as in the pathophysiology of occlusive vascular disorders.

Blood Platelets↗

Pharmacokinetics of estramustine phosphate (Estracyt) in prostatic cancer patients.

The pharmacokinetics of estramustine phosphate (EMP) was studied in five prostatic cancer patients given single i.v. and oral doses of EMP in a cross-over study. Plasma and urinary concentrations of parent drug, estramustine, estromustine (the estrone analogue), estradiol and estrone were followed by 32 h. The elimination of intravenous EMP from plasma was biphasic. The mean volumes of distribution were small, being 43 and 108 ml/kg for the central and peripheral compartments, respectively. The plasma clearance was 64 ml/kg/h, and the half-lives of the two phases were 0.16 and 1.27 h. Metabolism was the major route of elimination of EMP. It was readily dephosphorylated and oxidized to yield the cytotoxic metabolites estramustine and estromustine. Estromustine was the main metabolite in plasma. When given orally EMP underwent extensive presystemic dephosphorylation, which started in the gastrointestinal tract. The relative bioavailability of estromustine after administration of EMP-capsules was 44%, which reflects incomplete absorption of EMP rather than first-pass metabolism of estromustine. The terminal half-life of estromustine was 10-20 h, which suggests that EMP might be given once or twice a day.

Administration, Oral↗

In vivo metabolism of human tissue-type plasminogen activator.

The turnover of human tissue-type plasminogen activator (t-PA), purified from cell culture fluids and radiolabelled with 125I, was studied in 2 healthy males. After injection, the plasma radioactivity initially disappeared with a half-life of about 3 min, but after 30 min reached a plateau level which persisted for several hours. The radioactive material had then already been converted to forms soluble in 10% trichloroacetic acid (TCA). Surface counting rates indicated a rapid uptake in the liver during the first 10 min after injection, followed by a rapid release from the liver, beginning already at 25 min, which coincided with the appearance of the TCA-soluble radioactive material. After 18 h, about 80% of the injected dose had already been excreted in the urine. We conclude that, in humans, injected t-PA is rapidly cleared from the circulation, mainly by the liver, and within 30 min metabolized to low molecular weight forms which ultimately (within 1 d) appear in the urine.

Adult↗

Relevance of social and behavioral factors in the evaluation of dental health care for school children.

An interdisciplinary strategy based on a theoretical model for studying dental health was used to analyze the relevance of social and behavioral factors in the evaluation of dental health care for school children. The study comprised pupils who, after a total period of 5 years, differed in their experience with preventive regimens applying different principles of dental prevention. In 1979-80 social and behavioral data were collected by means of a postal questionnaire from altogether 234 pupils, aged 15-16 years, from two school areas. Clinical data, comprising scores for prevalence of plaque, gingivitis, and caries, were available from examinations in 1974, 1978, and 1979. The analysis of factors influencing the subjects' oral status demonstrated that material factors--the parents' education and employment, type of housing, and line of education--and physical factors--sex and prevalence of plaque, gingivitis, and caries at base line--all were of significance for the results obtained. No significant influence of home care climate (social/political factors), dental knowledge and attitudes, general foresightedness or carelessness (mental factors), or tooth-cleaning and sweet-eating habits (action factors) was found. Social and behavioral factors of significance exerted their influence regardless of the type and scope of the dental health care provided. Gingival health was far more a consequence of the professional tooth-cleaning regimen than dependent on the social and behavioral factors tested. No superior effect on caries status was demonstrated for any of the preventive regimens tested.

Adolescent↗

On the role of the C1-esterase inhibitor in cold urticaria.

Plasma samples from 20 patients with acquired cold urticaria were studied. The C1-esterase inhibitor activity was found to be low, but the total C1-esterase inhibitor concentration was normal. Prekallikrein, plasmin-alpha 2-antiplasmin complex, and kallikrein-like activity were also found to be within normal limits. Cold-promoted activation of coagulation factor VII occurred in 45% of the patient plasmas and resulted in a considerable drop in C1-esterase inhibitor activity.

Adolescent↗

The predictive value of three diagnostic procedures in the evaluation of palpable breast tumours.

In a prospective study of 200 palpable breast tumours of 200 women, the diagnostic specificity and sensitivity of clinical examination, mammography, and fine needle aspiration were compared, alone and in combinations. All tumours were excised and examined histologically, and 38 were malignant. The diagnostic sensitivity of clinical examination was high, 98% (91-99), whereas the specificity was rather low, 48% (36-60). No statistically significant differences were found between the sensitivities or the specificities of the three examinations. When the methods were combined the sensitivity was 100% (96-100) and the specificity was 37% (27-46). Statistically, no improvement of the diagnostic value could be shown. It is concluded that the possibility of distinguishing between malignant and benign palpable breast tumours is not increased by adding mammography and/or fine needle aspiration, but the discovery of two non-palpable malignant tumours by mammography underscores the importance of this method in disclosing subclinical malignant lesions. The study disclosed a statistical possibility of overlooking a few malignant tumours when using these three procedures. Therefore, we advise that all palpable breast tumours should be excised.

Biopsy, Needle↗

An enzyme linked immunosorbent assay for determination of tissue plasminogen activator applied to patients with thromboembolic disease.

Utilizing the immunoglobulin fraction from a goat antiserum against human uterine tissue plasminogen activator, an enzyme-linked immunoassay for tissue-type plasminogen activator in human plasma has been developed. With the new method, the concentration of t-PA in normal human acidified plasma is found to be 4.0 +/- 1.8 (SD) ng/ml. It increases to 12 ng/ml after a tourniquet test, and to 14 ng/ml after strenuous physical exercise. In a group of patients with idiopathic thromboembolic disease, the resting t-PA concentration was 5 ng/ml and the post-occlusion value 16 ng/ml. Furthermore, the patients also exhibited a normal post-occlusion rise in the concentration of plasmin-alpha 2-antiplasmin complex. However, in 37% of the post-occlusion patient plasmas, virtually no increase in t-PA could be detected by a specific activity assay. The results indicate that the reason for a defective post-occlusion fibrinolytic activity in a majority of cases may be the presence of increased concentrations of a fast-acting specific t-PA inhibitor.

Enzyme-Linked Immunosorbent Assay↗

Structural and circular-dichroism studies on the interaction between human C1-esterase inhibitor and C1s.

The reaction between complement factor C1s and C1-esterase inhibitor has been investigated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, N-terminal amino acid analysis and c.d. studies. It is confirmed that a very stable stoichiometric 1:1 complex with a molecular weight of about 180000 is formed, involving the light chain of C1s. On the sodium dodecyl sulphate/polyacrylamide gels a small peptide with a molecular weight of about 5000 can be seen, which may be released from the C-terminal portion of the inhibitor moiety in a manner analogous to that occurring in other similar proteinase-inhibitor reactions. By N-terminal amino acid analysis, a newly formed threonine residue is found in the complex, suggesting that the inhibitor peptide chain is cleaved in the complex between C1s and C1-esterase inhibitor. The stabilizing bond may therefore be an ester bond. C.d. studies of the native C1-esterase inhibitor indicated the presence of about 38% alpha-helix, about 24% beta-structure and about 38% unordered structure. By gradual cleavage of the disulphide bridges under non-denaturating conditions, gradual changes in the c.d. spectra occurred, suggesting loss of ordered secondary structures. The c.d. spectra of the complex between C1s and C1-esterase inhibitor indicate that tryptophan residues are affected by the complex-formation.

Amino Acids↗

On the interaction between human plasma kallikrein and C1-esterase inhibitor.

The kinetics of the reaction between human plasma kallikrein and C1-esterase inhibitor was studied in a purified system. By monitoring the inhibition reaction for extended periods of time, it was found to proceed in two consecutive steps, a fast reversible second-order binding step followed by a slower, irreversible first-order transition. The rate constants in this reaction model were determined, as well as the dissociation constant of the initial, reversible enzyme-inhibitor complex. Thus, at 37 degrees C the second-order rate constant k1 was found to be 5 X 10(4) M-1 . s-1, the first-order rate constant k2 was 5 X 10(-4) s-1, and the dissociation constant K was 1.5 X 10(-8) M. Heparin (28 U/ml) and 6-aminohexanoic acid (10 mM) had no effect on the k1 of the reaction.

Aminocaproic Acid↗

Kinetic study of the interaction between ribulosebisphosphate carboxylase/oxygenase and inorganic fluoride.

The effect of inorganic fluoride on the reactions catalyzed by ribulosebisphosphate carboxylase/oxygenase has been characterized with the fully activated enzyme. Fluoride inhibits both reactions, and the concentration required to inhibit the activity of the magnesium-activated enzyme 50% is 2 mM when reactions are carried out at pH 8.3. Inhibition is strongly pH dependent with an apparent pKa of 8.8. The inhibition kinetics were studied. It was found that inhibition is mixed but close to noncompetitive with respect to CO2 and uncompetitive with respect to ribulose 1,5-bisphosphate. The mechanism of interaction between fluoride and the enzyme is discussed, and a model is proposed in which fluoride interferes with the reactions by displacing a catalytically important ligand, probably a water molecule, from the activator metal.

Carboxy-Lyases↗