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Biomedical subjects

M Kjellberg

Publications and source records attributed to M Kjellberg.

At least 19 recordsLinked to original sources
PubMed2006

An immunochemical method for quantitative determination of latent antithrombin, the reactive center loop-inserted uncleaved form of antithrombin.

Antithrombin (AT) is a serine protease inhibitor that has thrombin, factors IXa and Xa as target proteases. In addition to active native AT, two other forms have been identified in plasma: the reactive center loop inserted cleaved and latent, uncleaved forms. Both have been shown to be present in normal human blood. Latent AT forms a dimer with native AT in vitro, thus inactivating the native form. Here we describe a mouse monoclonal antibody, 8C8, that is specific for latent AT. The affinity of 8C8 was found to be 500-fold higher for latent than for native AT and 5000-fold higher for latent than for cleaved AT. A sandwich assay was developed to measure the concentration of latent AT in plasma, which was found to be approximately 4.8 mg L(-1) in healthy individuals. The K(D) of the interaction between native and latent AT was found to be 51 mum, i.e. far above the plasma concentration of both native and latent AT, indicating a negligible complex formation in blood.

Adult↗
PubMed2006

The complex between activated protein C and protein C inhibitor: A clinically useful indicator of aortic aneurysms?

The concentration of the complex between activated protein C and the protein C inhibitor reflects the degree of activation of blood coagulation. A sandwich method has been devised that measures the complex concentration in blood plasma. A key feature of the method is that the catching monoclonal antibody recognizes a complex-dependent neoepitope in PCI, which is a prerequisite, since the concentration of uncomplexed PCI is approximately 10(4)-fold higher than that of the complex. In patients with atherosclerotic disease, those with aortic aneurysms exhibit a three-fold increase in complex concentration compared to that of normal subjects.

Aortic Aneurysm↗
PubMed2006

The cleaved and latent forms of antithrombin are normal constituents of blood plasma: a quantitative method to measure cleaved antithrombin.

Antithrombin (AT), a member of the serine protease inhibitor family, is the key regulator of thrombin activity in vivo. Thrombin inhibition is accomplished by the formation of covalent thrombin-AT (TAT) complex. The rate of inhibition is accelerated by heparin, which also leads to the formation of a substantial amount of cleaved AT. We produced a murine monoclonal antibody (mAb) (M9) that is specific for the two forms of AT, in which the reactive center loop is inserted into beta-sheet A, i.e. cleaved and latent AT. The antibody has no measurable affinity for native AT. Using M9 as a catcher antibody in conjunction with a mAb (M27) that does not bind latent AT, we developed a sandwich assay that measures cleaved AT without interference from latent and native AT. The concentration in healthy subjects was determined to be 1.3 mg L(-1) (range: 1.0-1.9), which was about 100-fold lower than the plasma concentration of native AT and 1000-fold higher than the concentration of the TAT complex. The cleaved AT concentration is higher than what would be expected from the rate of formation of cleaved AT in vitro in conjunction with TAT complex formation in the presence of heparin. The concentration of cleaved AT did not correlate with the TAT concentration in plasma from patients with venous thrombosis.

Animals↗
PubMed2005

Surface entropy of rare-gas clusters.

Abundances of ArN+ and XeN+ clusters produced in a supersonic expansion source are inverted to find relative dissociation energies. The values around the shell and subshell closings at N=55, 71, and 147 differ from theoretical values derived from ground-state energies of Lennard-Jones clusters. A significant part of the difference can be accounted for by the conformational entropies of surface atoms and vacancies.

Journal Article↗
PubMed2003

Pericardiocentesis guided by 2-D echocardiography: the method of choice for treatment of pericardial effusion.

BACKGROUND: Percutaneous pericardiocentesis guided by 2-D echocardiography has been used at Linköping Heart Centre since 1983. AIM: To evaluate our experience of this method including a follow-up and also to determine the aetiology of pericardial effusion. METHODS: A retrospective study including 120 of 252 consecutive patients punctured. RESULTS: The two most common aetiologies were cardiac surgery (77% valve surgery), followed by malignant disease. The postsurgical effusions became clinically important a median of 12 days after surgery (range 0-56 days). The median survival in the group with malignant disease was 89 days (30-day survival 87%, 1-year survival 10%). Indwelling catheter was used in 93% of the patients. There was no mortality but one patient needed a second pericardiocentesis after an accidental puncture of the right ventricle. Nine patients had rhythm aberrations. Recurring effusion that needed puncture was seen in 8%. CONCLUSION: Pericardiocentesis guided by 2-D echocardiography is a safe and efficient method to treat pericardial effusion and also valuable as palliative treatment for patients with malignant aetiology of the effusion.

Adult↗
PubMed2001

A sensitive immunochemical assay for measuring the concentration of the activated protein C-protein C inhibitor complex in plasma: use of a catcher antibody specific for the complexed/cleaved form of the inhibitor.

Activated protein C (APC) is a serine proteinase that regulates blood coagulation. In plasma it is inhibited mainly by the protein C inhibitor (PCI). The plasma concentrations of APC-PCI complex is increased in hypercoagulative states such as deep venous thrombosis. Formation of the APC-PCI complex induces a drastic conformational change in PCI that exposes new epitopes (neoepitopes) on the molecule. We have devised a simple immunofluorometric sandwich assay for measurements of the concentrations of APC-PCI complex, employing as the catcher, a monoclonal antibody that has a high affinity (K(D) = 4 x 10(-11) M) for a complexation-specific neoepitope that is expressed on PCI. A monoclonal antibody against protein C is employed as the tracer. The method gives a linear dose-response curve (0.06-50 microg/l), has a low detection limit (0.06 microg/l) and no crossreactivity with native PCI at physiologic plasma concentrations. We have now determined the concentration of the APC-PCI complex in healthy individuals.

Calibration↗
PubMed2000

Activated protein C-protein C inhibitor complex formation: characterization of a neoepitope provides evidence for extensive insertion of the reactive center loop.

Protein C inhibitor, a serine proteinase inhibitor (serpin), is the physiologically most important inhibitor of activated protein C. We have made a monoclonal antibody (M36) that binds with equally high affinity to an epitope present in activated protein C-protein C inhibitor complexes and cleaved loop-inserted protein C inhibitor. Insertion of a synthetic N-acetylated tetradecapeptide (corresponding to residues P1-P14 of the reactive center loop) into beta-sheet A of the uncleaved inhibitor also exposed the epitope. The antibody had no apparent affinity for native uncleaved inhibitor or for the free peptide. Synthetic P1-P14 analogues, with Arg P13 or Ala P9 substituted to the residues found in mouse protein C inhibitor (Thr and Ile, respectively), were also inserted in beta-sheet A. The Arg P13/Thr substitution led to a greatly impaired reactivity with the antibody, whereas the Ala P9/Ile mutation resulted in a modest loss of reactivity with the antibody. These results indicate that complex formation leads to insertion of the reactive center loop in beta-sheet A from Arg P14 and presumably beyond Ala P9. Moreover, to the best of our knowledge, this is the first instance where the neoepitope of a complexation-specific monoclonal antibody has been localized to the loop-inserted part of beta-sheet A, the part of the serpin where the complexation-induced conformational change is most conspicuous.

Animals↗
PubMed1984

Electroimmunoassay of sex hormone binding globulin. Enhanced sensitivity by autoradiography using A-ring 125I-17-beta-oestradiol.

Four different 125I-iodinated steroids were tested for their binding to human sex hormone binding globulin (SHBG) using an electrophoretic technique. 17-beta-oestradiol iodinated in its A-ring was found to bind with high affinity to SHBG. This radioactive steroid was used to increase the sensitivity of the electroimmunoassay of SHBG by adding the steroid to the samples before electroimmunoassay. The radioactive steroid incorporated into the immunoprecipitates could be observed by autoradiography. The sensitivity of the assay, which employed a rabbit antiserum against purified human SHBG and was standardized with pure SHBG, was about 0.2 mg/l. The precision of the method, calculated as the coefficient of variation within and between assays, was 2.4% and 2.6%, respectively, for values within the normal range. The mean SHBG concentration in healthy regularly menstruating women (n = 50) was 3.50 +/- 0.74 (SD) mg/l when measured in plasma, and 3.78 +/- 0.80 mg/l when measured in serum. The corresponding mean concentrations in healthy men (n = 28) were 2.26 +/- 0.45 mg/l in plasma and 2.44 +/- 0.49 mg/l in serum. The modified electroimmunoassay described in this paper is a simple modification, which increases the sensitivity sufficiently to permit reliable quantification of SHBG over the entire range of concentration which could be relevant in clinical practice.

Adolescent↗
PubMed1976

Studies of teratogenic effects of the dithiocarbamates maneb, mancozeb, and propineb.

Oral administration of high dosages of the dithiocarbamate pesticides maneb and mancozeb was teratogenic in rats but not in mice. The malformations, severe limb and craniofacial defects, were pronounced after maneb treatment but less so after mancozeb and propineb, zinc-containing compounds. The teratogenic effect of maneb was progressively reduced by simultaneously administering increasing amounts of zinc acetate. The mechanism of the teratogenic effect may involve the compounds being chelating agents, trapping zinc required for many important enzyme systems.

Abnormalities, Drug-Induced↗
PubMed1975

Developmental precocity in transferred mouse embryos influencing the teratogen response to salicylate.

Asynchronous blastocyst transfer, supposed to equalize the developmental stage of native and alien embryos during the organogenic period, was used as a tool in a teratological investigation. A spurious protection by the transfer as such was shown to depend on a persisting asynchrony between native and alien foetuses. The initial difference of 24 h was not nullified, but decreased to 8 h. This difference allowed transferred foetuses to pass the period of maximum sensitivity before salicylate treatment.

Abnormalities, Drug-Induced↗