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Biomedical subjects

K Karlsson

Publications and source records attributed to K Karlsson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Performance of a modified HIV-1 p24 antigen assay for early diagnosis of HIV-1 infection in infants and prediction of mother-to-infant transmission of HIV-1 in Dar es Salaam, Tanzania.

The aim of this study was to determine the utility of an amplified human immunodeficiency virus type 1 (HIV-1) p24 antigen (ag) assay using heated plasma or serum samples for the early diagnosis of HIV-1 infection in infants and for the prediction of the risk of mother-to-infant (MTI) transmission of HIV-1 in Dar es Salaam, Tanzania. The study included 125 samples from 76 infants positive for HIV-1 DNA by the polymerase chain reaction (PCR), 106 samples from 101 PCR-negative infants and 116 and 160 samples from seropositive and seronegative mothers, respectively. Samples were boiled to dissociate immune complexes and tested for HIV-1 p24 ag using a p24 ag amplification assay. Reactive samples were confirmed by a neutralization assay. Altogether, 123 of 125 samples from 76 PCR-positive infants were positive for p24 ag (sensitivity = 98.7%). HIV-1 p24 ag was found in all 18 samples collected at 1-8 weeks, in 35 of 36 samples collected at 9-26 weeks, in all 40 samples collected at 27-52 weeks, and in 30 of 31 samples collected > 52 weeks after birth. Detection of HIV-1 p24 ag was significantly more common in transmitting mothers (12 of 29, 41.4%) than in nontransmitting mothers (nine of 87, 10.3%) (p < 0.001). Among mothers with p24 antigenemia, the vertical transmission rate was significantly higher (12 of 21, 57%) than in mothers without p24 antigenemia (17 of 95, 18%) (p < 0.001). All samples from 101 PCR-negative children and 160 seronegative mothers were negative for p24 ag (specificity = 100%). We conclude that using heated plasma or serum increases the sensitivity of the p24 ag assay significantly. This modified simple test may be sufficient for the early diagnosis of HIV-1 infection in infants in settings with limited laboratory facilities. It is also useful for prediction of the risk of MTI transmission of HIV-1.

Biomarkers↗
PubMed1996

Protective effect of S-adenosyl-L-methionine on bromobenzene- and D-galactosamine-induced toxicity to isolated rat hepatocytes.

The protective effect of S-adenosyl-L-methionine (SAMe) on bromobenzene (BB)- or D-galactosamine (GalN)-induced damage to isolated rat hepatocytes and its effect on cellular glutathione (GSH) levels were investigated. SAMe at concentrations of 0.5 to 3.0 mmol/L significantly reduced lactate dehydrogenase leakage from cells exposed to 1.6 mmol/L BB (P < .05 to .001) during 2 hours' incubation. GalN at 25 to 50 mmol/L induced a marked increase of LDH leakage from the cells during the later stage of 24 hours' incubation and SAMe at 1.0 mmol/L clearly attenuated the LDH leakage in GalN (25 mmol/L)-exposed cells. The GSH content in the cells exposed to 2.4 mmol/L BB for 150 minutes was markedly decreased, and further decreased during 24 hours' incubation. SAMe (1.5 mmol/L) both reduced LDH leakage and corrected GSH depletion in cells exposed to 2.4 mmol/L BB. The GSH content in 25 and 50 mmol/L GalN-exposed cells was strikingly diminished to 51.2% and 32.8% of the controls, respectively, during 24 hours' of exposure. SAMe at 1.5 mmol/L significantly reduced the loss in GSH content in 25 mmol/L GalN-exposed cells. The findings show that SAMe has beneficial effects on both BB- and GalN-induced toxicity to rat hepatocytes. The main mechanism behind the protective effect of SAMe on BB and GalN toxicity seems to be associated with enhancement of GSH synthesis in the cells.

Animals↗
PubMed1996

Intra-articular hyaluronan injections in the treatment of osteoarthritis of the knee: a randomised, double blind, placebo controlled multicentre trial. Hyaluronan Multicentre Trial Group.

OBJECTIVE: To assess the effects of intra-articular injections of hyaluronan on symptoms of knee osteoarthritis (OA). METHODS: Two hundred and forty patients with symptomatic, radiological knee OA were randomly assigned to treatment with weekly injections for five weeks with either 25 mg of high molecular weight hyaluronan or vehicle. Results were evaluated at weeks 1, 2, 3, 4, 5, 13, and 20 by visual analogue scales (pain, function, motion, activity), algofunctional index, and global evaluation by patient and investigator. Analysis was by "intention to treat', "per protocol', and area under the curve principles on unstratified patient groups and for patients stratified into four groups of equal size by age and baseline algofunctional index. RESULTS: No serious side effects were reported. At 20 weeks both treatment groups were improved compared with baseline, with no difference between unstratified groups treated with placebo or hyaluronan. Comparison of treatment groups stratified by age and baseline algofunctional index revealed a significant difference in favour of hyaluronan over placebo (pain, activity, algofunctional index, global evaluations by patient and investigator) for patients older than 60 years and with a baseline algofunctional index greater than 10. There was no clinically relevant difference between the two treatments for the other three stratified subgroups of younger age or fewer symptoms. Similar results were obtained by area under the curve, intention to treat, and per protocol analysis. CONCLUSIONS: Patients older than 60 years with knee osteoarthritis and with significant symptoms corresponding to an index of severity of knee disease of 10 or more, comprise the group most likely to benefit from treatment with intra-articular hyaluronan injections.

Adult↗
PubMed1996

Protective effects of trolox C, vitamin C, and catalase on bromobenzene-induced damage to rat hepatocytes.

BACKGROUND/METHODS: The protective effects of trolox C (water-soluble vitamin E), vitamin C, and catalase on bromobenzene (BB)-induced toxicity to isolated rat hepatocytes were evaluated. The glutathione (GSH) content of the hepatocytes exposed to BB was measured. RESULTS: BB caused acute damage to the cells during 2 h of incubation (short) when BB was added directly to the culture wells, whereas a late-occurring and time-dependent increase in lactate dehydrogenase (LDH) leakage rate was observed during 24 h of incubation (long) when BB was dissolved in a different way. Incubation of the cells with trolox C (0.5-2.0 mM) prevented the hepatocellular damage induced by BB at 2.4 mM during the long-term incubation. Vitamin C (0.1-1.0 mM) had a protective effect on BB-induced toxicity during both the short- (BB, 1.6 mM) and the long- (BB, 2.4 mM) term incubations. Catalase (3200 U/ml) also showed a beneficial effect on the cells during the short-term BB exposure. Trolox C (2.0 mM) and vitamin C (0.5 mM) restored BB-induced GSH depletion in the cells. CONCLUSIONS: BB induced two patterns of LDH leakage from isolated hepatocytes on the basis of different ways of BB exposure and incubation periods. Trolox C, vitamin C, and catalase exerted protective effects on BB-induced toxicity during short- or/and long-term incubations. The effects were concentration-dependent. Restoration of GSH content in BB-exposed hepatocytes suggests that trolox C and vitamin C could reduce GSH consumption during BB metabolism and exert an antioxidant effect.

Analysis of Variance↗
PubMed1995

Glass-ceramic-coated titanium hip endoprosthesis. Experimental study in rabbits.

Titanium alloy hip endoprostheses coated with a bioactive glass ceramic (BGC) were followed in rabbits. All test endoprostheses remained stable, and image analysis showed an average of 78% bonding of the BGC-coated implants to bone at 52 weeks. The uncoated Ti-alloy controls demonstrated an average of 37% bone coverage after 52 weeks. By scanning electron microscopy the thickness of the BGC reaction layer was found to stabilize at 60 microns after bioactive bone bonding. The results indicate that the BGC coating must be thicker than the reaction layer to prevent detachment from the core metal.

Alloys↗
PubMed1995

Identification of Shigella and enteroinvasive Escherichia coli strains by a virulence-specific, monoclonal antibody-based enzyme immunoassay.

BALB/c mice were immunised with water extracts made from an Escherichia coli K-12 strain harbouring the shigella invasion plasmid, and hybridomas secreting antibodies specific to invasion plasmid-coded antigens were selected. On Western blots, antibodies produced by one of these clones (MAIC-1) recognised a protein of 43 kDa, which is the molecular mass of invasion plasmid coded antigen C (IpaC). When used in enzyme immunoassay against whole bacterial cells or against proteins secreted by actively growing bacteria, MAIC-1 clearly differentiated between invasive and non-invasive strains. Testing 123 enteroinvasive and 139 non-enteroinvasive strains the MAIC-1 based assay proved to be highly specific and sensitive in recognising enteroinvasive isolates. This test could be an inexpensive and rapid alternative to cumbersome virulence assays and a helpful technique in identifying Shigella or enteroinvasive Escherichia coli isolates.

Animals↗
PubMed1995

Safety and immunogenicity study of the auxotrophic Shigella flexneri 2a vaccine SFL1070 with a deleted aroD gene in adult Swedish volunteers.

The live auxotrophic Shigella flexneri 2a vaccine strain SFL1070 with a deleted aroD gene was given orally to 37 adult Swedish volunteers who received three doses within 5 days. Each dose comprised 1 x 10(5) (n = 9), 1 x 10(7) (n = 10), 1 x 10(8) (n = 9) or 1 x 10(9) (n = 9) c.f.u. S. flexneri SFL1070. One volunteer vaccinated with 1 x 10(7) and three vaccinated with 1 x 10(8) c.f.u. reported mild gastrointestinal symptoms after the first dose. Vaccination with 1 x 10(9) c.f.u. caused abdominal pain and watery diarrhoea in four volunteers who all recovered spontaneously within 72 h. S. flexneri SFL1070 was not recovered from volunteers given 1 x 10(5) c.f.u., but was shed in faeces by six volunteers vaccinated with 1 x 10(7), by all nine vaccinated with 1 x 10(8), and by seven volunteers vaccinated with 1 x 10(9) c.f.u. The mean excretion time was 2.6 (range 0-4) days in the 1 x 10(8) and the 1 x 10(9) groups. Serum antibody responses against either S. flexneri 2a and Y lipopolysaccharides (LPSs) or Shigella invasion plasmid antigens (Ipa) were seen in eight volunteers vaccinated with 1 x 10(9) (p < 0.01 to p < 0.05 for mean relative titres of IgA and IgG against S. flexneri 2a and Y LPSs), in four vaccinated with 1 x 10(8), and in two and one volunteers each vaccinated with 1 x 10(7) and 1 x 10(5) c.f.u. of S. flexneri SFL1070. Intestinal sIgA responses to the same antigens were elicited in all volunteers in the 1 x 10(9) and the 1 x 10(8) groups, and in six and one volunteers vaccinated with 1 x 10(7) and 1 x 10(5) c.f.u., respectively. The sIgA responses against S. flexneri 2a and Y LPSs were significant in all but the 1 x 10(5) group (p < 0.01 to p < 0.05). Significant antibody-secreting cell (ASC) responses specific to S. flexneri 2a LPS were seen in peripheral blood from eight volunteers each in the 1 x 10(9) and 1 x 10(8) groups and from five volunteers vaccinated with 1 x 10(7) c.f.u. (p < 0.01 to p < 0.05). The number of volunteers showing anti-Shigella Ipa ASC responses in these groups were five (p < 0.01 to p < 0.05), three and one, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1995

Early diagnosis of HIV-1 infection in infants in Dar es Salaam, Tanzania.

OBJECTIVES: To evaluate two simple methods, an immune complex dissociation (ICD) p24 antigen assay and an HIV-1-specific IgA antibody assay, for the early demonstration of HIV-1 infection in infants, using the polymerase chain reaction (PCR) as the reference method. DESIGN AND SETTING: Group A: 143 HIV-1-seropositive and 134 -seronegative mothers and their infants were recruited at delivery at the main hospital in Dar es Salaam, Tanzania. Group B: 26 HIV-PCR-positive hospitalized children in Dar es Salaam, 3-15 months old and suspected of having an HIV-related illness. METHODS: Blood samples were taken from mothers and infants in group A at intervals during the children's first 24 months and once from each of the children in group B. Peripheral blood mononuclear cells were tested by nested PCR for viral DNA. Plasma samples were tested by the Coulter p24 antigen (ag) enzyme-linked immunosorbent assay (ELISA) after acid dissociation of p24 antigen-antibody complexes. All p24-ag-positive reactions were confirmed by neutralization. Viral specific IgA antibodies were demonstrated in plasma by a modified ELISA. RESULTS: One hundred and sixty-three of 174 samples from seropositive mothers were PCR-positive (sensitivity 93.7%) and 612 of 614 samples from seronegative mothers and children of seronegative mothers were PCR-negative (specificity 99.7%). Twenty-nine of 145 (20.0%) children born to seropositive mothers were positive by PCR when tested during the first year of life. By use of both the p24 ag ELISA and the IgA antibody ELISA in combination, HIV-1 infection was detected in 9 of 17 (53%) PCR-positive children 1-8 weeks old, in 15 of 18 (83%) PCR-positive children 9-26 weeks old and in 23 of 24 (96%) PCR-positive children 27-52 weeks old. The specificities of the p24 ag ELISA and the IgA ELISA were 100%. CONCLUSIONS: The p24 ag assay and the IgA antibody ELISA, when used in combination, had a high sensitivity and specificity for detection of HIV-1 infection in infants, especially in those above the age of 6 months.

Journal Article↗
PubMed1995

The interstitium of the human arterial wall contains very large amounts of extracellular superoxide dismutase.

The levels of the secreted, interstitially located extracellular superoxide dismutase (EC-SOD), the cytosolic copper-and-zinc-containing SOD (CuZn-SOD), and the mitochondrial manganese-containing SOD (Mn-SOD) were measured in the walls of human coronary arteries, proximal thoracic aortas, and saphenous veins. The blood vessel walls, particularly the arteries, were found to contain exceptionally large amounts of EC-SOD, whereas the levels of CuZn-SOD and Mn-SOD were relatively low compared with other tissues. Analysis of EC-SOD by immunohistochemistry indicates an even distribution in the vessel wall, including large amounts of the arterial intima. Arterial smooth muscle cells were found to secrete large amounts of EC-SOD and likely are the principal source of the enzyme in the vascular wall. The EC-SOD concentration in the human arterial wall extracellular space is high enough to efficiently suppress the putative pathological effects of the superoxide radical, such as oxidation of LDL and reaction with nitric oxide to form the deleterious peroxynitrite. The levels of EC-SOD in the aortic wall are found to vary widely among species and were on average 6440 U/g in humans, 4340 U/g in the cow, 2660 U/g in the pig, 160 U/g in the dog, 770 U/g in the mouse. There were only moderate differences in the amounts of CuZn-SOD and Mn-SOD. This wide variation in EC-SOD content suggests that the susceptibility to pathologies induced by superoxide radicals in the vascular wall interstitium should vary widely among species.

Animals↗
PubMed1995

Bambuterol in the treatment of asthma. A placebo-controlled comparison of once-daily morning vs evening administration.

Once-daily morning (7 AM) vs evening (10 PM) administration of the terbutaline prodrug bambuterol (20-mg tablet dose) was investigated in a double-blind, cross-over, randomized, and placebo-controlled study involving 29 diurnally active patients with asthma. Terbutaline plasma concentration, spirometry, and drug tolerance were assessed during 39-h inpatient studies. A 7-day washout period separated each treatment. Mean 24-h plasma concentration was comparable for morning and evening bambuterol (13.2 vs 14.0 nmol/L). The Cmax for evening vs morning dosing was 17.2 vs 15.5 nmol/L (p < 0.02). The 24-h mean FEV1 was greater (p < 0.001) for bambuterol (morning: 3.2 L; evening: 3.4 L) vs placebo (2.9 L) as it was for FVC, FEF25-75%, and peak expiratory flow rate (PEFR), with the maximum effect at 4 AM independent of medication time. Evening dosing, however, resulted in greatest 7 AM (awakening) FEV1, FEV25-75, and PEFR (p < 0.03). With reference to corresponding-in-time placebo values, improvement in FEV1 at the end of the 24-h dosing intervals amounted to 0.34 L (13.5%) (p < 0.0004) and 0.35 L (15.9%) (p < 0.0012) with evening and morning bambuterol dosing, respectively. Side effects were greater for bambuterol than placebo, but not significantly so. Once-daily bambuterol therapy proved to be an effective treatment for asthma, whether administered in the evening or morning. Evening dosing seems best for nocturnal asthma since airway patency overnight and on awakening at 7 AM is most improved.

Adolescent↗
PubMed1995

Protective effects of calcium channel blockers on acute bromobenzene toxicity to isolated rat hepatocytes. Inhibition of phenylephrine-induced calcium oscillations.

BACKGROUND AND METHODS: Protective effects of verapamil, nifedipine, diltiazem, and ethylene glycol tetraacetic acid (EGTA) on acute bromobenzene (BB) toxicity to rat hepatocytes were evaluated, and cytosolic [Ca2+]i was monitored in single BB-exposed rat hepatocytes. Additionally, the effect of nifedipine on phenylephrine-stimulated calcium oscillations was investigated. RESULTS: BB at 0.8-2.4 mM increased the lactate dehydrogenase (LDH) leakage rate dose-dependently. Pretreatment with verapamil (25-35 microM), nifedipine (35-45 microM), diltiazem (25 microM), or EGTA (1.5-5 mM) markedly attenuated the BB-induced (1.6 mM) LDH leakage rate during 2 h of incubations. BB did not cause any detectable acute change in [Ca2+]i. BB interfered with phenylephrine-stimulated calcium oscillations, by blocking the oscillations in 58% of the cells and reducing the oscillation frequency in the rest. Nifedipine (100 and 200 microM) blocked the phenylephrine-induced calcium oscillations completely in 55% and 88% of the cells, respectively. CONCLUSIONS: The findings demonstrate that verapamil, nifedipine, diltiazem, and EGTA significantly protect rat hepatocytes against BB toxicity. BB interferes with phenylephrine-stimulated calcium oscillations. Nifedipine inhibits the oscillations at doses higher than those exerting a protective effect.

Animals↗
PubMed1994

10-fold increase in human plasma extracellular superoxide dismutase content caused by a mutation in heparin-binding domain.

Extracellular superoxide dismutase (EC-SOD) is a secretory SOD isoenzyme. 99% of EC-SOD is anchored to heparan sulfate proteoglycans in the tissue interstitium, and 1% is located in the vasculature in equilibrium between the plasma and the endothelium. Analysis of EC-SOD in plasma samples from 504 random blood donors revealed a common (2.2%) phenotypic variant displaying 10-fold increased plasma EC-SOD content. The EC-SOD in the plasma of these individuals, collected both before and after intravenous injection of heparin, displayed a reduced heparin affinity when compared with samples from normal individuals. The specific enzymatic activity was the same as that of normal enzyme. Nucleotide sequence analyses of two of the affected subjects revealed a nucleotide exchange resulting in a substitution of Arg-213 by Gly. The substitution is located in the center of the carboxyl-terminal cluster of positively charged amino acid residues, which defines the heparin-binding domain. Polymerase chain reaction-single-strand conformational polymorphism and allele-specific polymerase chain reaction showed that all 11 affected individuals are heterozygous, carrying the same single-base mutation. Recombinant EC-SOD containing this mutation had a reduced heparin affinity similar to that of EC-SOD C from variant persons. The high plasma activity can be explained by an accelerated release from the tissue interstitium heparan sulfate to the vasculature and should thus be accompanied by significantly reduced tissue EC-SOD activities.

Amino Acid Sequence↗
PubMed1994

Immune responses in Vietnamese children after a single dose of the auxotrophic, live Shigella flexneri Y vaccine strain SFL124.

The live, auxotrophic Shigella flexneri vaccine strain SFL124 was given in a single dose of 10(7), 10(8) or 10(9) colony forming units (cfu), respectively, to each of three groups of 10 Vietnamese children aged 9-14 years. The vaccine was well tolerated by all the children without any severe side effects such as diarrhoea or fever being observed. Mild symptoms were reported by five children. Only five children were found by culture to excrete SFL124 but, by PCR, 28 of 30 children were found to excrete the vaccine strain for up to 5 days (mean 2.8 days) with insignificant differences among the groups. Local mucosal immune responses and antibody secreting cell (ASC) responses to S. flexneri lipopolysaccharide (LPS) and invasion plasmid-coded antigens (Ipa) were elicited in the children in a dose-dependent manner. Doses of 10(9) cfu induced most prominent responses, followed by those of 10(8) and 10(7) cfu. The sIgA responses were the highest whereas the ASC were modest. High titres of serum antibodies to Shigella LPS and Ipa were found in all the children before ingestion of the vaccine which elicited increases in serum antibody titres in only a few of them. The immune response patterns seen indicate a booster rather than a primary response and may be a consequence of the endemic nature of shigellosis in Vietnam.

Adolescent↗
PubMed1994

Infection of donor lymphocytes with human T lymphotrophic virus type 1 (HTLV-I) following allogeneic bone marrow transplantation for HTLV-I positive adult T-cell leukaemia.

Human T lymphotrophic virus type 1 (HTLV-I) associated leukaemia has a poor prognosis even with chemotherapy. We describe a patient with adult T-cell leukaemia treated with allogeneic bone marrow transplantation from an HTLV-I negative identical sibling donor. During follow-up after bone marrow transplantation, HTLV-I could be repeatedly isolated inspite of anti-viral prophylaxis. The patient died of an acute encephalitis and HTLV-I could be detected in autopsy material from the brain. By a PCR-based technique using short tandem repeats (STRs) it was shown that the patient's haemopoiesis was of donor origin. This shows the infection of donor cells in vivo by an aetiological agent which has been implicated in the leukaemogenic process for adult T-cell leukaemia.

Bone Marrow↗
PubMed1994

Mucosal immune responses in calves orally vaccinated with a live auxotrophic aroA Salmonella dublin strain.

The mucosal immune responses were studied in two calves orally vaccinated with the live aroA mutant strain, Salmonella dublin SL5631, and in two non-vaccinated control calves. Intestinal secretions were collected through a permanent fistula in place during a 5-week period. Vaccinated calves responded with high IgM and IgA titres against the S. dublin lipopolysaccharide. Both IgA and the IgM titres appeared already after 3 days and IgM somewhat earlier than the IgA titres. Both antibody titres remained high for 2 weeks after the third and final vaccine dose. The calves also showed marked T-cell responses in lymphocytes collected from mesenterial lymph nodes and the spleen.

Animals↗