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Biomedical subjects

A Larsson

Publications and source records attributed to A Larsson.

At least 271 records · Page 15Linked to original sources

Immunohistochemical and ultrastructural characterization of autoimmune sialoadenitis in aging BDF1 mice.

To further the understanding of the immunopathologic mechanisms involved in spontaneous autoimmune sialoadenitis of aging BDF1 mice, immunohistochemical and ultrastructural studies were undertaken. Eighteen of 19 aging BDF1 mice, 23-27 months of age, developed sialoadenitis spontaneously. By light and electron microscopy, it was observed that the submandibular gland lesion was characterized by mononuclear cell infiltration in the periductal and perivascular areas often accompanied by parenchymal destruction. Immunohistochemically, T cells predominated. The ratio of CD4+ to CD8+ T cells ranged from 0.5:1 to 2.9:1, with an average of 1.4:1. It seems likely that not only CD4+ cells, but also CD8+ cells, play a major role in submandibular gland inflammatory reactions of aging BDF1 mice.

Aging↗

Urinary fibronectin in diagnosis and follow-up of patients with urinary bladder cancer.

The levels of fibronectin in urine from 106 patients with urinary bladder cancer, from 13 patients with benign urological disease and from 24 healthy control individuals were determined by an enzyme-linked immunosorbent assay (ELISA). The fibronectin levels in urine from patients with bladder cancer were higher than in patients with benign urothelial disease and in healthy controls. In 9 patients with bladder cancer, sampling was done both pre- and post-operatively. In these cases the fibronectin levels after operation were significantly lower than they had been before. Among 14 patients treated with BCG intravesically for superficial bladder tumours, those with complete remission of disease had less urinary fibronectin than those who did not respond to treatment. The data suggest that urinary fibronectin may be a useful marker for detecting urinary bladder cancer and for selecting patients for BCG treatment.

Albuminuria↗

Specificity and levels of oral and systemic antibodies to Actinobacillus actinomycetemcomitans.

Salivary and gingival crevicular fluid antibodies and systemic antibodies were analysed for levels and specificity against Actinobacillus actinomycetemcomitans components. The major reactivity of salivary and serum IgA1 and IgA2 antibodies to the periodontal pathogen A. actinomycetemcomitans was against bands between 14 and 83 kD for IgA1 and bands between 14 and 68 kD for IgA2 in Western blot. In addition to specific binding, there was also a hitherto unrecognized Fc-mediated binding of IgG antibodies to an A. actinomycetemcomitans component around 50 kD. Serum IgG antibodies to A. actinomycetemcomitans leukotoxin displayed the highest median value and only 1 individual showed salivary IgM antibodies in ELISA. Elevated levels of gingival crevicular fluid IgA2 antibodies indicated a local production of IgA from periodontal tissues. Using synthetic peptides, several distinct epitopes on the leukotoxin were recognized by both salivary and serum IgA antibodies.

Aggregatibacter actinomycetemcomitans↗

Lung protein leakage in feline septic shock.

The aim of the present study was to explore lung microvascular leakage of protein and water in a feline model of septic shock, using a double isotope technique with external gamma camera detection and gravimetric lung water measurements. The experiments were performed on artificially ventilated cats. One group of cats (n = 8) was given an infusion of live Escherichia coli bacteria, and another group (n = 5) served as a control group receiving saline. Plasma transferrin was radiolabeled in vivo with indium-113m-chloride, and erythrocytes were labeled with technetium-99m. The distribution of these isotopes in the lungs was continuously measured with a gamma camera. A normalized slope index (NSI) was calculated, indicative of the transferrin accumulation corrected for changes in local blood volume that reflect protein leakage. In the septic group there was a protein leakage after bacterial infusion, with a NSI of 39 x 10(-4) +/- 5 x 10(-4) min-1 (mean +/- SEM), and the PaO2 diminished from 21 +/- 1 to 9.5 +/- 1 kPa. In control cats a slight protein leakage with a NSI of 9 +/- 10(-4) +/- 2 x 10(-4) min-1 was detected, probably caused by the operative procedure, but PaO2 did not change. Wet-to-dry-weight ratios of postmortem lungs were not significantly different between the groups. It was concluded that an intravenous infusion of live E. coli bacteria induces a lung capillary protein leakage without increased lung water and a concomitantly disturbed gas exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Glucose production rate in extremely immature neonates (< 28 weeks) studied by use of deuterated glucose.

Neonatal hypoglycemia is a frequent complication in immature infants. This may be due to small substrate stores, a high brain:body weight ratio, and immature enzyme systems. The purpose of the present study was to investigate the rate of glucose production in newborn infants with gestational ages of less than 28 wk. The subjects were 10 newborn infants delivered after 25 to 26 gestational wk. Their mean birth weight was 772 g (range 588-1000 g), and their mean postnatal age at the time of the study was 15 h (range 4-24 h). An isotopic compound (D-6,6-2H2-glucose) was given as a constant-rate i.v. infusion. In addition to dideuteroglucose, eight of the infants also received an i.v. infusion of unlabeled glucose at a rate of 1.4-2.6 mg.kg-1.min-1. Blood samples for determination of the concentration and isotopic enrichment of plasma glucose were obtained every 15 min in a 2-h period. Isotopic enrichment, measured by gas chromatography/mass spectrometry, was used for calculating the glucose production rate. The mean glucose production rate related to body weight (+/- SD) was 6.1 +/- 1.5 mg.kg-1.min-1. The results show that infants born at < 28 gestational wk have a capacity to produce glucose on their 1st d of life at rates close to or even exceeding those reported in term infants.

Blood Glucose↗

Chicken antibodies: taking advantage of evolution--a review.

Laying hens are highly cost-effective as producers of antibodies compared with the mammals traditionally used for such production. Also, chicken antibodies have biochemical advantages over mammalian antibodies due to the phylogenetical differences between avian and mammalian species, resulting in increased sensitivity as well as decreased background in immunological assays. In contrast to mammalian antibodies, chicken antibodies do not activate the human complement system nor will they react with rheumatoid factors, human anti-mouse IgG antibodies, or bacterial and human Fc (fragment crystallizable)-receptors. Thus, chicken antibodies offer many advantages over mammalian antibodies and may replace such antibodies in the future.

Animals↗

Deficient synthesis of cysteinyl leukotrienes in glutathione synthetase deficiency.

Glutathione synthetase deficiency (GSD) is an inborn error of glutathione (GSH) metabolism. As a consequence of the block in the gamma-glutamyl cycle, the enzyme defect leads to a generalized intracellular GSH deficiency. The cysteinyl leukotrienes (LTs), LTC4, LTD4 and LTE4, are potent lipid mediators generated in the 5-lipoxygenase pathway. LTC4 is derived from the unstable epoxide LTA4 by conjugation with GSH, and therefore GSH is required for LTC4 synthesis. In the circulation LTC4 is rapidly metabolized to LTE4 which is excreted in the urine. In the present study, LT metabolites were separated in a patient with biochemically established GSD and intracellular GSH deficiency (0.5 mM in erythrocytes, normal range 2.0-2.5 mM) by reversed-phase high-performance liquid chromatography, and quantified by enzyme immunoassays. Our results revealed that in GSD LTC4 synthesis is significantly decreased in calcium ionophore A23187-activated monocytes as well as in neutrophils (11-14% and 7-10%, respectively, of the levels detected in the parents or healthy controls). Additionally, urinary LTE4 was also found to be abnormally decreased in GSD (0.4 nmol/mol creatinine as compared to 15-46 nmol/mol creatinine in parents and controls). GSD represents the first described disorder with decreased synthesis of cysteinyl LTs and may serve as a unique model for the linkage between LT synthesis and GSH metabolism in vivo. Moreover the impaired synthesis of cysteinyl LTs might be involved in the pathophysiology of GSD.

Cysteine↗

Chicken antibodies: a tool to avoid interference by complement activation in ELISA.

MicroELISA plates coated with mammalian IgG will activate the human complement system. It has been shown that this activation of the complement system may interfere in solid-phase immunometric assays, and that there is a difference between IgG from different species and between different IgG subclasses in their ability to activate the human complement system. We have studied the ability of mammalian IgG and avian IgG to activate the human complement system. We show that chicken IgG do not activate the human complement system, and chicken IgG can thus be used in solid-phase immunometric assays to reduce interference by complement activation.

Animals↗

Studies of fibrinogen binding to platelets by flow cytometry: an improved method for studies of platelet activation.

Platelet function is dependent upon membrane receptors and their interaction with other proteins. Platelet activation appears to cause a structural change of the glycoprotein IIb/IIIa complex that exposes the fibrinogen binding site, which subsequently binds fibrinogen. Fluorescence-activated flow cytometry (FACS) is an efficient method for studying membrane proteins. Flow cytometry gives single-cell data, allowing the detection of only a small proportion of labelled platelets in whole blood without any washing steps. One problem with this method is that the labelled antibodies and the antigen, if present in plasma, form an immune complex, which may cause false positive reactions due to interaction between mammalian IgG and Fc gamma receptors on the platelets. We show that immune complexes with chicken IgG do not activate human platelets. We have developed a method for measuring platelet-bound fibrinogen in whole blood and platelet-rich plasma utilising fluorescein isothiocyanate (FITC)-conjugated chicken antibodies directed towards human fibrinogen. As low as 1% activated platelets could be detected without interference from Fc-interactions.

Adenosine Diphosphate↗

Genetic regulation of human anti-malarial antibodies in twins.

Immune responses to defined antigens may differ between individuals in a population as the reflection of differences in genetic regulation. In experimental animals, variation in responsiveness to a given epitope may be due to major histocompatibility complex (HLA, in humans) class II restrictions, implying serious limitations for the development of subunit vaccines. For human populations, knowledge of the relative importance of genetic as opposed to environmental factors affecting the immune response is scarce. We have compared antibody levels after immunization through repeated infections to a major malarial antigen (Pf155/RESA) in monozygotic twins with those in dizygotic twins, siblings, or unrelated controls. Antibody responses to the intact antigen and to some of its immunodominant epitopes were found to be more concordant within monozygotic twin pairs than in dizygotic pairs or age- and sex-matched siblings living under similar environmental conditions. The results support the conclusion that the antibody responses were genetically regulated. When the responses were assessed for possible associations with different HLA class II DRB, DQA, and DQB alleles had haplotypes, no associations were found. This suggests that the regulation of the Pf155/RESA antibody responses seen in this study reflects the impact of factors encoded by genes outside the HLA class II regions.

Adolescent↗

Does the shunt opening pressure influence the effect of shunt surgery in normal pressure hydrocephalus?

Thirteen patients with normal pressure hydrocephalus were operated upon with an externally maneuverable shunt system (Sophy SU8) in order to investigate its influence on clinical outcome, intracranial pressure and cranial CT parameters. The opening pressure was set at high at surgery and lowered stepwise at intervals of three months to medium and low. The clinical condition, intracranial pressure and cranial CT parameters were examined at the end of the 3 months interval on each pressure level. The patients improved within the first 3 months inspite of an unchanged mean intracranial pressure and remained in a stable clinical condition during the rest of the study period. The intracranial pressure was significantly reduced at 9 months. The ventricular index, Evans index, temporal horn and third ventricle width were reduced 3 months post-operatively and did not change significantly during the rest of the study. The pre-operative third ventricle width was correlated to high psychometric test results after shunt surgery. Reduction in ventricular index, Evans index and third ventricle width after surgery correlated to improvement in psychometric scoring. The clinical improvement after shunt surgery for normal pressure hydrocephalus is seen within 3 months and is independent of the adjusted valve pressure.

Aged↗

Salivary gland involvement in autoimmune thyroiditis, with special reference to the degree of association with Sjögren's syndrome.

From a total of 63 patients with autoimmune thyroiditis, 19 cases were further investigated to determine the degree of concomitant morphologic and functional salivary gland changes. For comparison, 21 of a total of 28 cases of primary Sjögren's syndrome were also examined. Of the 19 cases of autoimmune thyroiditis, 11 showed various degrees of salivary gland involvement on the basis of an analysis of lower lip salivary gland biopsy specimens, scintigraphy of the parotid, and unstimulated whole sialometry. Six of these cases fulfilled the criteria of primary Sjögren's syndrome. A remarkably high proportion of dark-staining acini was observed in the lower lip biopsy specimens of our patients with thyroiditis (8 of 19, 42%) and less among our patients with primary Sjögren's syndrome (5 of 21, 24%). We conclude that significant involvement of salivary glands may occur in cases of autoimmune thyroiditis, which indicates that common mechanisms may frequently be operative in the development of thyroid and salivary gland immune disease.

Adult↗

Chicken anti-protein A for the detection and capturing of protein A from Staphylococcus aureus in the presence or absence of mammalian IgG.

A sandwich-ELISA for the detection of protein A from Staphylococcus aureus (SpA) is described, using chicken anti-protein A as a capture antibody and its alkaline phosphatase conjugate for the detection of bound protein A. Traditionally, protein A is detected by its binding to the Fc part of a detector antibody. This binding will be influenced by the presence of other IgG in the protein A solution. However, SpA does not react with the Fc part of chicken IgG, and it is thus possible to detect protein A in IgG containing solutions, such as eluates from protein A-columns. The method can be used to detect 1 x 10(-7) g protein A/l in the presence of serum. The method is more sensitive if no serum or IgG is present in the solution.

Animals↗

Chicken antibodies: a tool to avoid interference by human anti-mouse antibodies in ELISA after in vivo treatment with murine monoclonal antibodies.

Human anti-murine antibodies (HAMA) can be found in serum of many patients who have received murine monoclonal antibodies for diagnosis or therapy. These antibodies are known to give false positive results in sandwich-type assays (e.g. ELISA or RIA). This interference problem will increase in the future as more patients are treated with murine monoclonal antibodies in vivo. HAMA can also be found in sera from patients that has not been treated with monoclonal antibodies. In this work we have studied the interference of HAMA in sandwich ELISAs containing antibodies from different species. HAMA, present in the sample, may react both with the capture antibody and the detection antibody in these assays to give a false positive reaction. HAMA did not react with chicken IgG, and if one of (or both) the capture and detection antibody was of avian origin, the interference of HAMA in sandwich assays could be avoided.

Animals↗

Pulmonary effects of body position, PEEP, and surfactant depletion in dogs.

The influence of position (sphinx, lateral, supine), surfactant depletion, and different positive end-expiratory pressure (PEEP) on functional residual capacity (FRC), series dead space (VdS) and compliance of the respiratory system (Crs) were evaluated in five dogs. Ventilation homogeneity as measured by an index (multiple breath alveolar mixing efficiency), oxygenation, and cardiovascular hemodynamics were additionally examined. The dogs were anesthetized with halothane, paralyzed, and mechanically ventilated. FRC and VdS were found to be notably large in dogs, 45 +/- 8 ml/kg and 6 +/- 1 ml/kg, respectively. FRC and ventilation homogeneity were improved in the sphinx position (prone position with upright head). Surfactant depletion by lung lavage with 37 degrees C saline caused an immediate and stable decrease in FRC, Crs, and oxygenation (P less than 0.05, respectively) for about 5 h without marked effects on the circulatory system. FRC and VdS increased with increasing PEEP. At the highest PEEP, 10 cmH2O (1 kPa), Crs decreased (P less than 0.05) and ventilation became more uneven, indicating alveolar overdistension.

Animals↗

Elimination of apparatus dead space--a simple method for improving CO2 removal without increasing airway pressure.

During mechanical ventilation the apparatus dead space can be eliminated by insufflating through one lumen of a tracheal double-lumen tube and allowing expiration through the other. In six intravenously anesthetized pigs, this technique resulted in an 18% (1 kPa) decrease in PaCO2 compared with insufflating through both lumens (32 ml rebreathing volume). Oxygenation, airway pressures, and tidal volumes were unchanged. Flushing the trachea with fresh gas during the expiratory phase did not improve the efficiency of ventilation. It is concluded that elimination of apparatus dead space improves CO2 removal without increasing airway pressures and tidal volumes, and it is suggested that minimization of apparatus dead space should be tried before more advanced ventilatory modes are considered.

Animals↗

Functional residual capacity and ventilation homogeneity in mechanically ventilated small neonates.

A modification of a computerized tracer gas (SF6) washout method was designed for serial measurements of functional residual capacity (FRC) and ventilation homogeneity in mechanically ventilated very-low-birth-weight infants with tidal volumes down to 4 ml. The method, which can be used regardless of the inspired O2 concentration, gave accurate and reproducible results in a lung model and good agreement compared with He dilution in rabbits. FRC was measured during 2-4 cmH2O of positive end-expiratory pressure (PEEP) in 15 neonates (700-1,950 g), most of them with mild-to-moderate respiratory distress syndrome. FRC increased with body weight and decreased (P less than 0.05) with increasing O2 requirement. Change to zero end-expiratory pressure caused an immediate decrease in FRC by 29% (P less than 0.01) and gave FRC (ml) = -1.4 + 17 x weight (kg) (r = 0.83). Five minutes after PEEP was discontinued (n = 12), FRC had decreased by a further 16% (P less than 0.01). The washout curves indicated a near-normal ventilation homogeneity not related to changes in PEEP. This was interpreted as evidence against the presence of large volumes of trapped alveolar gas.

Body Weight↗