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Biomedical subjects

A Larsson

Publications and source records attributed to A Larsson.

At least 253 records · Page 14Linked to original sources

Inhibition of fibrinogen binding to platelets by MK-852, a new GPIIb/IIIa antagonist.

MK-852 is a newly developed low molecular weight inhibitor of fibrinogen binding to platelets. Platelet aggregation and adhesion of platelets to damaged vessel walls are critical events in haemostasis, and uncontrolled aggregation may cause arterial thrombus formation. Depending on the location of the occluded vessel, this may result in unstable angina, myocardial infarction or stroke. Platelet aggregation requires binding of fibrinogen to the GPIIb/IIIa receptor on the platelet surface. Thus, inhibitors of fibrinogen binding to the receptor may constitute an efficient way of preventing thrombus formation. We have used flow cytometry and FITC-labelled chicken anti-human fibrinogen antibodies to study the in vitro inhibitory effects of MK-852 on fibrinogen binding to platelets. We show that MK-852 is a very efficient fibrinogen receptor antagonist in vitro. Flow cytometry is well suited for clinical use and may be used to monitor treatment with MK-852 or other fibrinogen receptor antagonists.

Animals↗

Characterization of regulatory T-cell responses in humans induced by the P. Falciparum blood stage antigen Pf155/RESA.

T-cells have a major role both as helper cells for efficient antibody production and as inducers and effector cells in antibody-independent malaria immunity. Thus, antigens to be included into a subunit vaccine must contain T-cell epitopes to become effectively immunogenic. The P. falciparum blood stage vaccine antigen Pf155/RESA has been shown to contain T-helper epitopes inducing T-dependent anti-malarial antibodies in vitro. We have also shown that synthetic peptides representing sequences from the amino-acid repeat regions of Pf155/RESA stimulate T-cells from P. falciparum primed donors to proliferate, to release IFN-gamma and/or IL-4. In individual donors there was no correlation between these different activities. Rather, they were frequently negatively associated. However, IL-4 secretion could be induced in T-cells from donors who had elevated concentrations of serum antibodies to the same peptide as used for T-cell activation. Taken together the results support the occurrence of malaria-specific CD4+ T-cell subsets (e.g. TH1 and TH2) in humans similar to what has been found in mice and suggest the involvement of TH2-type helper cells in the induction of some important P. falciparum specific antibodies. CD4+ T-cells recognize the antigen in the context of MHC class II molecules. However, in human outbred populations no consistent MHC restrictions of anti-Pf155/RESA immune responses could be demonstrated. This is not surprising in view of the extensive polymorphism of the HLA system. Neither were there any obvious MHC class II restrictions seen when antibody- and t-cell responses were measured in naturally primed monozygotic twins.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Outcomes of geriatric discharge planning. A quality assurance study from a geriatric rehabilitation ward.

The outcome of a discharge planning procedure at a geriatric rehabilitation ward was studied with an interdisciplinary and multidimensional approach, where medical, nursing, functional and psychosocial factors were included. The patient's own expectations and attitude to functional performance and outcome were explored in an interview at the day of discharge and one month later in a follow-up telephone interview. Data were also collected from registers and medical and professional records. All the 36 patients discharged to their own homes, mostly after home assessment, or to old people's homes were followed up. The median rehabilitation stay was 30 days. Their medical status was stable over time and nursing interventions remained frequent. The functional level was unchanged for 18, and further enhanced for 10 patients. Most patients felt secure at home and received the home help they anticipated. Worries were expressed by one-third on realistic grounds, mainly medical or ideas on the accommodation. Some interventions were required and carried out by the team. Home living was as expected or better for two-thirds of the patients. The timing and the patient's situation at discharge seemed to have been well assessed, with an overall positive outcome after a month at home. Further development of practical multidimensional evaluations adapted to elderly patients is necessary in a quality assurance perspective.

Activities of Daily Living↗

Plasma-cell gingivitis in children and adults. A clinical and histological description.

Plasma-cell gingivitis (PCG) is a rare, non-symptomatic lesion found in the attached gingiva. In the county of Södermanland 14 cases of PCG were identified during the last 13 years. Clinically, the PCG is a sharply demarcated red area within the attached gingiva. Abundant plasma cells are found in the connective tissue beneath a thin epithelium. Lesions with similar clinical appearance were also found in the genital mucosa of five of the patients with a PCG. An extensive bacterial plaque was frequently found on the gingiva and teeth in the affected areas. Although an improved oral or genital hygiene did not heal the lesions, an allergic reaction to the bacterial plaque may be the cause.

Adolescent↗

Leukotriene receptor antagonism prevents lung protein leakage and hypoxaemia in a septic cat model.

Products of the arachidonic acid cascade have been found to play an important role in the pathophysiology in experimental shock and in ARDS. The effect of cysteinyl-leukotriene (cLT) blockade on the development of respiratory failure during septic shock was examined. Ventilated cats received an infusion of Escherichia coli bacteria. Pretreatment was given with diethylcarbamazine (DEC), a leukotriene synthetase inhibitor, or a new potent cLT receptor antagonist, ICI 198,615. With a gamma camera, the distributions of plasmatransferrin radiolabelled with indium-113m chloride (113mIn) and erythrocytes radiolabelled with technetium-99m (99mTc) were measured over the lungs. A normalized slope index (NSI) reflecting protein leakage, based on the transferrin extravasation, was calculated. In the nonseptic control group (n = 7) NSI was 4.4 x 10(-4) +/- 0.7 x 10(-4).min-1 (mean +/- SEM). Unpretreated septic animals (n = 7) showed a protein leakage after bacterial infusion, with a NSI of 34 +/- 3.5 x 10(-4).min-1. Pretreatment with DEC (n = 6) significantly reduced NSI to 16 +/- 1.5 x 10(-4).min-1. In the group pretreated with ICI 198,615 (n = 8), NSI was 9 +/- 1.2 x 10(-4).min-1. Arterial oxygen tension (PaO2) remained at baseline level of 20 +/- 1.0 kPa during the experimental period in both the nonseptic control group and the ICI 198,615 pretreated group. In the unpretreated septic group, PaO2 fell progressively from a preseptic value of 21 +/- 0.9 to 12 +/- 1.5 kPa after 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

[Aurora].

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Counseling↗

HgCl2-induced glandular pathosis in the brown Norway rat.

Low doses of HgCl2 induce a genetically restricted autoimmune syndrome in Brown Norway (BN) rats (BN(Hg)). Part of the syndrome includes spontaneously developing mononuclear cell foci in salivary and lacrimal glands, morphologically similar to focal sialoadenitis in Sjögren's syndrome in man. In this study, we have shown that Hg-induced focal adenitis in BN rat is not female predominant and not solely dependent on Hg uptake in the glands. In BN(Hg), focal adenitis was found to develop in several different glands (parotid, submandibular, lacrimal, thyroid) as a specific manifestation of immunopathosis induced by Hg in the RT1n-haplotype-carrying BN. Such manifestations were absent in another strain, the Hg-resistant Lewis (RT1l). Also a potent contact sensitizer, DNFB, induced focal adenitis in isolated glands, provided that strong sensitization had occurred. Immunohistochemical characterization of focal adenitis in BN(Hg) with monoclonal antibodies showed that T cells and dendritic cells dominate the early infiltrates, whereas B cells were absent.

Animals↗

Prenatal analysis in two suspected cases of glutathione synthetase deficiency.

Prenatal diagnosis was performed in a family affected by generalized glutathione synthetase deficiency. The disorder is transmitted by autosomal recessive inheritance. The first child born in this family died of the disorder at 6 weeks of age. Prenatal diagnosis was performed in two subsequent pregnancies. Amniotic fluid samples were collected by amniocentesis in the 16th and 17th weeks of pregnancy, respectively. In the case of the second pregnancy the concentration of 5-oxoproline in the amniotic fluid was measured by stable isotope dilution, while both stable isotope dilution and glutathione synthetase activity measurements were employed in the prenatal analysis of the third pregnancy. The 5-oxoproline concentration in the second pregnancy was even lower than that of the controls and in the case of the third pregnancy the results fell within the control range. The second pregnancy resulted in the birth of a clinically healthy girl, and the outcome of 5-oxoproline concentration in a urine sample taken just after birth confirmed the unaffected state. The third pregnancy resulted in the birth of a healthy boy at term, and the 5-oxoproline concentration in his urine and the glutathione synthetase activity in haemolysates were determined. The results confirmed that this infant was also unaffected and he apparently had two normal alleles for the enzyme.

Amniotic Fluid↗

Biotin labelling of chicken antibodies and their subsequent use in ELISA and immunohistochemistry.

Avian antibodies have many advantages to mammalian antibodies due to the phylogenetic differences between birds and mammals, resulting in an increased sensitivity and a decreased background in many immunological assays. Since the avidin-biotin system is an efficient detection system for antibodies with a high sensitivity, we wanted to investigate the activity and unspecific binding of optimally biotin labelled chicken antibodies in ELISA and immunohistochemistry. We report on the conditions for biotinylation of chicken antibodies and that optimally biotinylated antibodies show a high activity and a low background in both ELISA and immunohistochemistry.

Animals↗

Analysis of a human monoclonal antibody reactive with multiple Plasmodium falciparum antigen repeat sequences using a solid phase affinity assay.

A solid-phase affinity assay was set up for the determination of the affinity of the interaction between the human monoclonal antibody (mAb) 33G2 and peptides corresponding to repeated sequences in three blood stage antigens of the malaria parasite Plasmodium falciparum. The epitope of this mAb is of interest due to the parasite blocking capacity of the mAb. Previous studies with PEPSCAN have defined the minimal epitope for the mAb as the pentapeptide VTEEI, a sequence frequently found in antigen Pf332. In the previous study, epitopes responsible for the cross-reactivity of the mAb with antigens Pf155/RESA and Pf11.1 were also identified. In the affinity assay described herein, the mAb was coated on a solid phase and binding of a labelled peptide was displaced by homologous or heterologous peptides. The affinity of peptides corresponding to Pf332 increased with increasing length, and the highest affinity was displayed by a dimer (23 amino acids) of a Pf332 repeat (K = 1.9 x 10(8) M-1). Peptide length did not influence the binding of peptides corresponding to the Pf155/RESA and Pf11.1 repeats, which had lower affinities comparable to that of the shortest Pf332 octapeptide (K = 2.2 x 10(4) M-1). Only peptides containing binding sites as defined by PEPSCAN analysis showed a measurable binding. When using peptides as inhibitors in peptide ELISA, binding correlated with the affinity of the peptides, but only the high affinity peptides were inhibitory. In contrast, a poor correlation was found when peptides were used directly for coating in ELISA.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Chicken anti-protein G for the detection of small amounts of protein G.

Streptococcal protein G, similar to staphylococcal protein A, is the Fc-binding proteins that seems best suited for affinity-purification of mouse, rat or human monoclonal antibodies. We have developed a sandwich-ELISA for monitoring of protein G leakage from such columns. It utilizes microtitre plates coated with chicken anti-protein G to capture protein G, and biotinylated chicken anti-protein G to detect bound protein G. Chicken IgG is one of a very few IgG that does not show any Fc reactivity with protein G. It is thus possible to make an antigen-specific assay for protein G. This assay can be used to detect protein G in IgG containing solutions, such as monoclonal antibody preparations. The method can be used to detect 1 x 10(-7) g protein G/1 in the presence of human serum or human IgG.

Animals↗

Exogenous surfactant therapy increases static lung compliance, and cannot be assessed by measurements of dynamic compliance alone.

OBJECTIVE: To study the immediate effects of exogenous surfactant therapy on blood gases, lung volumes, and lung mechanics in adult rabbits with experimentally induced respiratory distress syndrome. DESIGN: Prospective randomized, controlled study. SETTING: Laboratory and animal facility of a large university. SUBJECTS: Twelve adult New Zealand white rabbits. INTERVENTIONS: Respiratory failure was induced by repeated bilateral whole-lung lavage with saline (30 mL/kg body weight). After the last lavage, the animals were randomly assigned to two groups. Group 1 received surfactant (120 mg/kg body weight) that was suspended in a 0.6% sodium chloride solution. Group 2 received comparable volumes of the same hypotonic solution and served as controls. MEASUREMENTS AND MAIN RESULTS: Before and after endotracheal surfactant instillation, blood gases and functional residual capacity were measured, and lung mechanics from tidal volumes and pressure-volume curves were calculated. Functional residual capacity was measured by a computerized, multiple-breath, washin-washout method using sulfur hexafluoride (SF6) as tracer gas. The pressure-volume curves were obtained by an occlusion technique originally described for measuring static breath-by-breath compliance. The technique was modified for present use and fully computerized. Within 60 mins after surfactant instillation, there were marked improvements in Pao2 (61 +/- 7 torr [8.2 +/- 0.9 kPa] to 470 +/- 47 torr [62.6 +/- 6.2 kPa]) and in functional residual capacity (7.6 +/- 1.4 to 17.7 +/- 1.6 mL/kg body weight) at unchanged ventilatory settings. The pressure-volume curves became steeper over time and the pressure-volume curves for total lung volume were restored to an almost normal state. Maximum compliance calculated from the pressure-volume curves increased by 92% but there was no significant change in dynamic compliance. In the control group, no improvements in any measured or calculated lung parameters were seen. CONCLUSIONS: The findings indicate that during mechanical ventilation, the effects of surfactant therapy on lung mechanics are best characterized by changes in functional residual capacity and maximum compliance obtained from static pressure-volume curves and not by dynamic compliance.

Animals↗