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Biomedical subjects

A Larsson

Publications and source records attributed to A Larsson.

At least 199 records · Page 11Linked to original sources
PubMed1997

Oral, perioral and systemic pathosis in HgCl2-induced autoimmunity in the BN rat.

Male BN rats were repeatedly skin-injected with HgCl2 solution and sacrificed after 6, 9, 14, 21, 28 or 24 days. Mononuclear cell infiltrates were observed in the oral mucosa and in lacrimal, salivary and thyroid glands from 6-9 days onwards, with a peak at 14-21 days. Immunohistochemistry identified these cells as predominantly T cells with some NK cells but very few B cells. Reversible parenchymal changes were observed but there was no obvious persistent tissue destruction. Serum titers of IgE, IgG1, anti-laminin and anti-DNP, but not IgG2a antibodies, were raised and peaked at 14-21 days. However, there was no correlation, within animals, between these titers and the extent of mononuclear cell infiltration. Mercury was histochemically detected within dendritic cells/macrophages in the connective tissue stroma of the glands and in the oral mucosa, but no correlation was found between the distribution of mercury and the degree of inflammation. We conclude that the accumulation of mononuclear cells in oral and perioral tissues of HgCl2-treated BN rats does not represent a local immune response to tissue-retained Hg. Instead, we propose that the extravasation represents an epiphenomenon that is not necessarily deleterious to the infiltrated organ.

Animals↗
PubMed1997

Linear growth in early treated children with congenital hypothyroidism.

Length/height was studied from birth to 6 years of age in 103 children with congenital hypothyroidism identified by the Norwegian or Swedish screening programs. We used the "infancy-childhood-puberty (ICP) growth model". This model describes normal linear growth during the first 3 years of life by an infancy component with the addition of a childhood component, the latter acting from the second half of the first year. In comparison with reference children, children with hypothyroidism had reduced growth from 6 to 12 months, and increased growth after 12 months of age. Mean onset of the childhood component of growth was delayed from 8.1 months (SD 1.9) to 10.4 months (SD 2.2) in girls, and from 8.9 months (SD 2.0) to 11.0 months (SD 2.1) in boys. Age at onset of the childhood component was correlated with age at start of treatment (r = 0.24), and in children with more severe hypothyroidism (pretreatment serum thyroxine < 40 nmol/l) inversely correlated with the L-thyroxine dose at start of treatment (r = -0.40). Change in height standard deviation score from 1 to 3 years of age was correlated with the serum thyroxine concentration at age 1 year (r = 0.30). The delay in the onset of the childhood component of growth and the association with age at start of treatment and initial L-thyroxine dose indicate that thyroid hormones during the first months of life are essential for normal onset of the childhood component of growth, which otherwise is assumed to be growth hormone-dependent.

Age Factors↗
PubMed1997

The timing of glucocorticoid administration in rheumatoid arthritis.

OBJECTIVE: To test the hypothesis that the timing of prednisolone administration might be critical in determining its effect on the diurnal rheumatoid inflammatory process. METHODS: 26 patients with rheumatoid arthritis were randomly divided into two equal groups and allocated to low doses of prednisolone at either 2.00 am or 7.30 am. Because of the diurnal variation in disease activity in rheumatoid arthritis, assessments of the two study groups were performed at 7.30 am both at the start of the study (day 1) and after four doses of prednisolone (day 5). The study protocol differences in the time period from the last dose of prednisolone to assessment were 5.5 hours in the 2.00 am group and 24 hours in the 7.30 am group. RESULTS: Administration of low doses of prednisolone (5 or 7.5 mg daily) at 2.00 am had favourable effects on the duration of morning stiffness (P < < 0.001), joint pain (P < 0.001), Lansbury index (P < < 0.001), Ritchie index (P < < 0.001), and morning serum concentrations of IL-6 (P < 0.01). The other study group showed minor but significant effects on morning stiffness (P < 0.05) and circulating concentrations of IL-6 (P < 0.05). Modest and similar improvements of C reactive protein, serum amyloid protein A, and erythrocyte sedimentation rate were seen in both study groups. CONCLUSIONS: Administration of low doses of glucocorticoids with a rather short biological half life seems to improve acute rheumatoid arthritis symptoms if it precedes the period of circadian flare in inflammatory activity, as defined by enhanced IL-6 synthesis. Further studies are needed to test the relative merits of different timing protocols of glucocorticoid administration in rheumatoid arthritis.

Aged↗
PubMed1997

Beneficial effect of cold dialysate for the prevention of hemodialysis-induced hypoxia.

Hypoxia occurs frequently during routine hemodialysis (HD). In this study the effect of dialysate temperature on arterial blood gas parameters was investigated. Ten stable HD patients (2 smokers) were dialyzed for 240 min with each of three different dialysate temperatures: 36.5 degrees C (normal temperature HD; NHD), 38.5 degrees C (warm HD; WHD) and 34.5 degrees C (cold HD; CHD). A cuprophane plate dialyzer was used. The ultrafiltration volume was identical in each patient. Arterial blood gas samples were frequently (approximately 10 times/treatment) taken during the dialysis and immediately analyzed. The dialysate temperature significantly affected PaO2 (p < 0.001) but not PaCO2. We also compared the effect of NHD with that of WHD and CHD, respectively, as regards PaO2. NHD and WHD differed significantly p < 0.01), whereas NHD and CHD were not significantly different. However, the relative PaO2 value (% of the baseline value) at the end of CHD (105 +/- 5%) was significantly higher than after both NHD (96 +/- 4%, p < 0.01) and WHD (91 +/- 3%, p < 0.01). In the case of NHD and WHD the fraction of time during which the patients had a PaO2 value below 80 mm Hg was 62 and 64%, respectively. The corresponding figure for CHD was 44%. Arterial oxygen saturation (SaO2) increased during CHD from 95.2 +/- 0.6 to 96.7 +/- 0.6% (p < 0.05), while SaO2 was unchanged during NHD and WHD. The positive effect of CHD was evident in 7 patients. In 1 patient PaO2 was not affected by the dialysate temperature, while in the remaining 2 patients (smokers) a decrease in PaO2 was induced by WHD as well as CHD. A separate statistical analysis with the 2 smokers excluded was performed, which showed that the dialysate temperature significantly affected PaO2 (p < 0.001). A comparison between NHD and CHD showed a significant difference (p < 0.001), whereas NHD and WHD did not differ significantly. When the 2 smokers were excluded from the analysis the fraction of time with a PaO2 value below 80 mm Hg was 60% during NHD and 56% during WHD, but it was reduced to 31% during CHD. In conclusion, despite the existence of interindividual variations most patients seemed to benefit from cold dialysate for the prevention of dialysis-induced hypoxia.

Adult↗
PubMed1997

Attenuated hepatic glucose production but unimpaired lipolysis in newborn infants of mothers with diabetes.

In infants of diabetic mothers, maternal-fetal hyperglycemia induces fetal hyperinsulinemia, which may be sustained for several hours after birth. The inhibitory effect of insulin on glycogenolysis, gluconeogenesis, and lipolysis increases the risk of hypoglycemia in these infants. Eight term infants of diabetic mothers were studied between 3.9 and 8.5 h postnatally. The maternal diabetes was considered well controlled as judged by self-monitoring of blood glucose and Hb Alc. Neonatal plasma concentrations of glucose, glycerol, and insulin were monitored and averaged 2.7 +/- 0.7 mM, 371 +/- 116 microM, and 15.9 +/- 2.8 microU.mL-1, respectively. Stable isotope-gas chromatography/ mass spectrometry techniques were used to determine glucose and glycerol turnover rates and gluconeogenesis from glycerol in the infants. The appearance rates of glucose and glycerol averaged 20.0 +/- 5.4 mumol.kg-1.min-1 (3.6 +/- 1.0 mg.kg-1.min-1), and 8.9 +/- 2.3 mumol.kg-1.min-1, respectively. The fraction of glycerol appearance rate converted to glucose was 68.2 +/- 17.3%, which accounted for 15.5 +/- 4.6% of glucose production. Thus, compared with healthy term infants studied previously under identical conditions, the infants of diabetic mothers had higher insulin concentrations and attenuated glucose production. Despite increased insulin concentrations, lipolysis was unimpaired, and the gluconeogenic contribution from glycerol was higher than in the healthy newborns.

Birth Weight↗
PubMed1997

Morphology of endogenous flare-up reactions in contact allergy to gold.

In a double-blind study, 20 patients with contact allergy to gold were given an intramuscular injection of gold sodium thiomalate or placebo, inducing a clinical and histological flare-up of healed patch test sites in the gold-injected but not in the placebo group. The test area of the placebo group showed some perivascular lymphocytic foci (UCHL-1+) and vascular endothelial ELAM-1 staining. The gold group, with flare-up, showed larger and more extensive lymphocytic foci with ELAM-1+ endothelium as well as lymphocytic epidermotropism. CD1a+ LC cells were downgraded, tryptase+ mast cells accumulated and CD68+ monocytes/macrophages markedly increased. Probably, a significant part of the tissue priming as a result of patch testing comprises memory T-cells and endothelial ELAM-1 upgrading, but blood-borne CD68+ monocytes may also be instrumental in the flare-up.

Antigens, CD↗
PubMed1997

Anti-human prostasome MAB 78 binds to antigen distinct from PSA and PAP.

PURPOSE: The characteristics of an antigen corresponding to a monoclonal antibody (mAb 78) against human prostasomes were compared with prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP). The correspondence of Ag 78 to two other prostate-derived antigens, prostasin and peptide pGlu-Phe-Pro-NH2, were also considered. MATERIALS AND METHODS: The immunoreactivity of mAb 78 and the cross-reactivity of mAb 78 with PSA and PAP were studied with immunohistochemical and enhanced chemiluminescence (ECL) Western blotting methods. RESULTS: The mAb 78 did not bind to PSA blots, and anti-PSA antibody did not label prostasome blots. Neither did PSA and PAP impede the binding of mAb 78 onto prostasome blots nor to paraffin sections of prostate epithelium. Afer Western blots, mAb 78 bound diffusely to a band with a molecular weight of 35 kDa, but did not bind to PSA 933 kDa) or PAP (monomer 50 kDa, intact molecule 100 kDa) bands. From purified 35 kDa bands, three fractions were sequenced, which showed no similarities to PSA and PAP. CONCLUSIONS: The Ag 78 is different from PSA and PAP, and probably also from prostasin and peptide pGlu-Phe-Pro-NH2. The mAb 78 can be used as a new marker for human prostasomes.

Acid Phosphatase↗
PubMed1996

Structural and functional characterization of two mutated R2 proteins of Escherichia coli ribonucleotide reductase.

The R2 protein of ribonucleotide reductase from Escherichia coli is a homodimeric tyrosyl-radical-containing enzyme with two identical dinuclear iron centers. Two randomly generated genomic mutants, nrdB-1 and nrdB-2, that produce R2 enzymes with low enzymatic activity, have been cloned and characterized to identify functionally important residues and areas of the enzyme. The mutations were identified as Pro348 to leucine in nrdB-1 and Leu304 to phenylalanine in nrdB-2. Both mutations are the results of single amino acid replacements of non-conserved residues. The three-dimensional structures of [L348]R2 and [F304]R2 have been determined to 0.26-nm and 0.28-nm resolution, respectively. Compared with wild-type R2, [L348]R2 binds with higher affinity to R1, probably due to increased flexibility of its C-terminus. Since the three-dimensional structure, iron-center properties and radical properties of [L348]R2 are comparable to those of wild-type R2, the low catalytic activity of the holoenzyme is probably caused by a perturbed interaction between R2 and R1. The [F304]R2 enzyme has increased radical sensitivity and low catalytic activity compared with wild-type R2. In [F304]R2 the only significant change in structure is that the evolutionary conserved Ser211 forms a different hydrogen bond to a distorted helix. The results obtained with [F304]R2 indicate that structural changes in E. coli R2 in the vicinity of this helix distortion can influence the catalytic activity of the holoenzyme.

Bacterial Proteins↗
PubMed1996

Monoclonal antibodies against unfertilized zona-free mouse oocytes: characterization and effects on fertilization.

A panel of anti-oocyte antibodies was raised against unfertilized zona-free mouse oocytes by intrasplenic immunization and checked for their effects on in vitro fertilization. Four antibodies decreased the fertilization rate from about 90% in controls to 8% (B5-2 F7), 12% (A2-2 A7), 13% (4-G1), and 25% (A2-2 F2), when the sperm cell concentration was 1 x 10(5) to 1 x 10(6). Antigen localization: All the antibodies labelled components in the cell membrane of zona-free oocytes as demonstrated by indirect immunofluorescence and/or by complement-mediated oocyte lysis. In various patterns, the ooplasm and zona pellucida were also labelled with different intensities. Western blotting: A2-2 A7 and A2-2 F2 recognized a protein with a molecular weight of approximately 65 kDa, while antibody B5-2 F7 bound a 97 kDa protein. Complement activation and complement-mediated oocyte lysis: Systemically injected antibodies, C3 and C4 were detected on zona-free oocytes recovered from the mouse oviduct indicating the activation of C3 and C4 by antigen-antibody complexes. The recovered oocytes were not damaged, suggesting a presence of complement-regulating factors. In vitro, however, a large number of zona-free oocytes preincubated with antibodies were lysed or protruded ooplasma vesicles in complement-active serum. Stage, tissue, and species specificity: None of the antibodies, except A2-2 A7, showed a positive immunolabelling to the pronuclear stage. Antibodies 4-G1 and A2-2 F2 cross-reacted with the ovarian oocytes. No antibodies bound to any of the tissues tested, indicating that the corresponding antigen epitopes are not commonly expressed. A2-2 A7, A2-2 F2, and B5-2 F7 cross-reacted with hamster and human unfertilized oocytes, suggesting the presence of developmentally conserved molecules and the possibility to apply these antibodies in hamster and human in vitro fertilization. It is concluded that the approach used could be a useful strategy in searching for anti-fertilization antibodies for human contraception.

Animals↗
PubMed1996

Influence of optical probing with YOYO on the electrophoretic behavior of the DNA molecule.

The influence of the fluorescent dye YOYO (1,1'-(4,4,8,8,-tetramethyl- 4,8-diazaundecamethylene)bis[4-[[3-methyl-benzo-1,3-oxazol-2 -yl] methylidene]-1,4-dihydroquinolinium] tetraiodide) on the electrophoretic behavior of the DNA molecule was investigated. This is important when using YOYO as a probe in capillary electrophoresis or in fluorescence microscopy studies of DNA with the purpose of studying the migration mechanism of DNA on the molecular level. We have measured the mobility and orientation dynamics (using the linear dichroism technique) for both pure DNA and the YOYO-DNA complex in agarose gel in order to compare their electrophoretic properties. Mobility decreases, the degree of orientation becomes lower, and the orientational dynamics slower, when YOYO binds to DNA. However, the dependence on field strength of the mobility, orientation and orientational dynamics, are similar for DNA and YOYO-DNA, indicating that the mode of migration does not change significantly upon binding YOYO to DNA. Furthermore, since our results show that the effect of YOYO on both the degree of orientation and orientational dynamics of the DNA can be measured and therefore be compensated for, it can be concluded that YOYO is an excellent optical probe for the study of the migrational behavior of DNA.

Bacteriophage T7↗
PubMed1996

Simulations of the overshoot in the build-up of orientation of long DNA during gel electrophoresis based on a distribution of oscillation times.

The periodic extension-contraction motion observed for long DNA molecules undergoing agarose gel electrophoresis in a constant field is believed to be important for the separation mechanism in pulsed field gel electrophoresis. These oscillations give rise to an overshoot and an undershoot in the ensemble orientation of DNA in the beginning of a field pulse, when the molecules oscillate coherently. After approximately one oscillation cycle, the coherence between the molecules is lost, and a constant, cycle-averaged orientation is reached. In this paper we simulate this build-up of the ensemble orientation of DNA by using a distribution of oscillation times (the time between two consecutive compressed conformations) determined by fluorescence microscopy for YOYO-stained DNA. Six different orientation profiles, describing the orientation during one oscillation cycle, were used. The simulated orientation responses are compared with an orientation response measured by linear dichroism (LD) under the same experimental conditions as in the microscopy study. We found that the choice of orientation profile during the oscillation is important. Best agreement between the simulated and the experimental orientation response was obtained for an orientation profile based on a theoretical model by Schurr and Smith (Biopolymers 1990, 29, 1161-1165). The influence of the distribution of oscillation times and its standard deviation on the orientation response was also investigated. Furthermore, simulations at different field strengths and DNA sizes were performed and found to agree quite well with the experimentally obtained LD data.

Computer Simulation↗
PubMed1996

Activated platelets and impaired platelet function in intensive care patients analyzed by flow cytometry.

Intensive care patients often have disturbances in their coagulation and fibrinolysis systems, which may result in haemorrhage or disseminated intravascular coagulation (DIC). DIC is a dreaded complication that may develop rapidly and has a high mortality rate. Platelets play a central role in haemostasis and it is thus important to have assays that rapidly can monitor platelet activation and platelet function. We have used flow cytometry to measure platelet activation and function in intensive care patients. Fluorescein labelled chicken antibodies were used to detect platelet bound fibrinogen as these antibodies have advantages over mammalian antibodies in flow cytometry. We found increased levels of circulating activated platelets and microparticles in vivo and impaired platelet function after stimulation in vitro. The two patients with the highest percentage of microparticles died shortly after blood sampling.

Disseminated Intravascular Coagulation↗
PubMed1996

Hypophosphatasia affecting the permanent dentition.

Reports on dental abnormalities in connection with hypophosphatasia almost exclusively describe changes in primary teeth. A 23-year-old man with hypophosphatasia, first diagnosed at the age of 8 months, is described; histologically and radiographically verified signs of the condition were present in the permanent dentition. The findings included a reduced level of the marginal alveolar bone supporting the upper central incisors, which had to be extracted. The molars displayed large coronal pulp chambers. Histologically, the upper incisors demonstrated abnormal root cementum, with areas of dentin resorption, as well as disturbances of the mineralization of the coronal dentin. The patient also had signs of abnormal root resorption of molars. The potential involvement of permanent teeth puts children with hypophosphatasia at risk of developing oral complications during adolescent and adult life.

Adult↗
PubMed1996

Human autoantibodies recognizing human and mouse preimplantation stages.

PROBLEM: To find out whether autoantibodies against human preimplantation stages are present in some human sera and, if so, whether the antibodies could be capable to affect the egg development and/or to trigger an activation of the complement system at the procedures of assisted conception. METHODS: 1. Immunohistochemistry on blots of human preimplantation stages. 2. Immunohistochemistry on paraffin sections of human and mouse preimplantation stages. 3. Culture of mouse morulae to analyze complement activation. RESULTS: 1. Some human sera contained autoantibodies against human preimplantation stages. 2. Human-mouse cross-reacting antibodies against preimplantation stages occurred. 3. Immune complexes, formed on mouse preimplantation stages, activated the complement systems in egg cultures, resulting in a damaging of the eggs. CONCLUSION: The presence of natural autoantibodies to preimplantation stages may be associated with reproduction failure, caused by a direct effect by the autoantibodies and/or an activation of the uterine complement system by the immune complexes formed.

Animals↗
PubMed1996

Experimental graft versus host disease in the (BN x LEW) F1 rat hybrid: an immunohistochemical study of early disease in oral mucosa.

OBJECTIVE: To study the initial cellular events in oral mucosa (tongue) of experimental hyperplastic GVHD, in order to increase our understanding of the possible pathogenic mechanisms that may be shared with eg mercury (and other drug)-induced immunological reactions. MATERIALS AND METHODS: GVHD was induced by one i.v. injection of 0.5-1 x 10(8) BN spleen cells into (BNxLEW)F1 hybrid rats. The pre-onset stages of the developing semiallogeneic GVHD were investigated in tongue mucosa by immunohistochemistry and monoclonal antibodies. RESULTS: No detectable tissue infiltrates were found 24 h post induction. The pioneer cells appeared at day 3 and were RTIB+/CD2+ and RTIB1-/CD45 (240 kD)-/ EDI-/CD45RC-. At day 3, there was also a visible increase in spleen and lymph node size. Between day 3 and 7, there was a statistically significant increase of CD2+, RTIB+, TCR-alpha beta+, CD4+ and CD8+ cells, but no increase of NKR-PI+ cells. At day 10 there were focal accumulations of CD8+ and NKR-PI+ cells in subepithelial c.t. and in the basal parts of the adjacent epithelium. Animals not sacrificed earlier, showed signs of disease onset at day 11-14. CONCLUSIONS: The early inflammatory infiltrate in this GVHD model consists of activated T cells of donor origin. We suggest, that these originally 'naive' cells migrate initially into lymphoid tissue and following an activation (day 3) enter host's peripheral tissue. Here, (allo-) antigen in constitutively RTIB1 (and EDI) expressing connective tissue dendritic cells may be immune targets of the primed T cells. Such interaction may lead to focal inflammation (increase of CD2+, RTIB+, TCR-alpha beta+, CD4+ and CD8+ cells) and to secondary epithelial damage executed by CD8+ and NKR-PI+ lymphocytes.

Analysis of Variance↗