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Biomedical subjects

B Jansson

Publications and source records attributed to B Jansson.

At least 37 records · Page 2Linked to original sources
PubMed1999

The effect of ketoconazole on the jejunal permeability and CYP3A metabolism of (R/S)-verapamil in humans.

AIMS: The purpose of this human intestinal perfusion study was to investigate the effect of ketoconazole on the jejunal permeability and first-pass metabolism of (R)- and (S)-verapamil in humans. METHODS: A regional single-pass perfusion of the jejunum was performed using a Loc-I-Gut(R) perfusion tube in six healthy volunteers. Each perfusion lasted for 200 min and was divided into two periods of 100 min each. The inlet concentration of (R/S)-verapamil was 120 mg l-1 in both periods, and ketoconazole was added at 40 mg l-1 in period 2. (R/S)-verapamil was also administered as a short intravenous infusion of 5 mg, over a period of 10 min. The appearance ratios of the CYP3A formed metabolites (R)- and (S)-norverapamil were also estimated in the outlet jejunal perfusate. RESULTS: The effective jejunal permeability (Peff) of both (R)- and (S)-verapamil was unaffected by the addition of ketoconazole in period 2 suggesting that ketoconazole had no effect on the P-glycoprotein mediated efflux. However, the appearance ratio of both (R)- and (S)-norverapamil in the outlet jejunal perfusate decreased in the presence of ketoconazole. The rate of absorption into plasma of (R)- and (S)-verapamil increased despite the low dose of ketoconazole added, indicating an inhibition of the gut wall metabolism of (R/S)-verapamil by ketoconazole. CONCLUSIONS: Ketoconazole did not affect the jejunal Peff of (R/S)-verapamil, but it did increase the overall transport into the systemic circulation (bioavailability), probably by inhibition of the gut wall metabolism of verapamil. This might be due to ketoconazole being less potent as an inhibitor of P-glycoprotein than of CYP3A4 in vivo in humans.

Adult↗
PubMed1999

Subjective future as a mediating factor in the relation between pain, pain-related distress and depression.

The coincidence of chronic pain, psychological distress and depression has been well documented in several studies. However, there is still debate about the type of causality linking these factors and whether psychological distress and depression precede or are a consequence of pain. This study contributes to this debate through an analysis of the latent structure behind these complex concepts. To test the hypothesis that subjective future (i.e. how the pain patient perceives the future) has an impact on pain, data were analysed from 660 chronic pain patients who were tested with The Multidimensional Pain Inventory (MPI), The Symptom Distress Checklist (SCL-90) and a Future Scale, which was constructed from items of the Sense of coherence-scale. By use of path analysis and structural equation modeling (S.E.M.) four latent constructs were tested: Pain, Interference, Distress and Subjective future. The results indicated that Subjective future has a strong impact on Distress, is a mediating variable, which contributes to conceptually explaining and practically nullifying the relationship between Pain and Distress, and finally that Pain is a concept, that changes with increasing duration. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗
PubMed1999

Population UV-dose and skin area--do sunbeds rival the sun?

From the perspective of skin cancer risks, sunbed tanning may give the population group of Swedish adolescents a yearly total dose in terms of ultraviolet radiant energy to the skin which is comparable to sunlight. For populations, a dosage scheme is applied, where exposed skin area is estimated to be two to ten times larger in tanning units than in outdoor sunlight. The normal dose fluence rate is multiplied by the exposure time and by the exposed body surface area. A study of sunbed use among adolescents was reinvestigated. Skin dose from artificial tanning in that population group is calculated and compared to sun exposure for erythemally effective radiation and for UVA (315-400 nm). Skin doses from tanning units to the adolescent population agree with estimates based on information concerning sunbed lamp sales/year. For the population, the erythemal skin dose from tanning units exceeds an increase in solar ultraviolet radiation to the skin projected from 10% ozone depletion. The dosage scheme might help to interpret data suggesting an increased melanoma risk among young people using sunbeds > or = 10 times per year. Tanning and sunburns in sunbeds and in sunlight is discussed with regard to skin area.

Adolescent↗
PubMed1999

Unintentional injury mortality in children: a priority for middle income countries in the advanced stage of epidemiological transition.

OBJECTIVES: To examine the relationship between the magnitude, and the relative importance of unintentional child injury mortality with socioeconomic development, and to conceptualise the dynamic changes in injury mortality within the framework of epidemiological transition. DESIGN: Ecological cross sectional study using data on 51 countries. MAIN OUTCOME MEASURES: The relationship between total mortality rates, unintentional injury mortality rates, and percentage in children 1-14 years of age with gross national product (GNP) per capita. RESULTS: Unintentional injury mortality rates in children were negatively correlated with GNP per capita. However, by categorising the data, we found some areas of non-correlation: in children 5-14 years in low income versus lower middle income countries, and in all age and gender groups in lower high income versus higher high income countries. A high percentage of total deaths due to injuries was clearest in the lower middle income countries in all age and gender groups. CONCLUSIONS: The changes in child injury mortality in relation to socioeconomic development could be conceptualised as three stages: a stage of high magnitude; a stage of high priority; and a stage of improvement. Most middle income countries are in the high priority stage where both injury mortality rates and injury percentage of total deaths are high.

Adolescent↗
PubMed1998

All individual domains of staphylococcal protein A show Fab binding.

The interactions between the individual domains (E, D, A, B and C) of staphylococcal protein A (SPA) and Fc and Fab regions of human immunoglobulins were studied using real-time biospecific interaction analysis. An engineered domain Z, similar to fragment B but with a single glycine to alanine amino acid substitution, was also included in the study. The domains were expressed in Escherichia coli, affinity purified and immobilised onto sensor chip surfaces in a directed manner using a unique C-terminal cysteine residue engineered into the recombinant proteins. All domains bound to a recombinant human IgG1 Fc fragment with similar strength. For the first time, binding to human Fab was demonstrated for all native SPA domains, using both polyclonal F(ab')2 and a recombinant scFv fragment as reagents. Interestingly, the engineered Z domain showed a considerably lower affinity for Fab as compared to the native domains.

Amino Acid Sequence↗
PubMed1997

Stimulation of proliferation in human colon cancer cells by human monoclonal antibodies against the TF antigen (galactose beta1-3 N-acetyl-galactosamine).

In many tissues, the TF (Thomsen-Friedenreich) blood group antigen (Galbeta1-3GalNAc alpha-) behaves as an onco-foetal carbohydrate antigen, showing increased expression in malignancy and hyperplasia. Dietary lectins which bind the TF antigen have marked effects on proliferation of epithelial cells without cytotoxicity. This led us to speculate that anti-TF antibodies, including those that naturally occur in humans, might have similar effects. Five anti-TF antibodies, TF2 (human), TF5 (human), 5A8 (mouse), 8D8 (mouse) and BM22 (mouse), but not TFI (human) or 49H.9 (mouse), showed marked dose-dependent stimulation (95-192%) of [3H]thymidine incorporation by HT29 human colon cancer cells. Similar stimulation of proliferation of HT29 cells by these monoclonal antibodies (MAbs) was found when cell count assessment was used. Antibody-stimulated proliferation was inhibited by co-incubation with glycoproteins expressing Galbeta1-3GalNAc alpha- (asialo glycophorin or [Galbeta1-3GalNAc alpha-O-p-aminophenyl]n-human serum albumin). A proliferative effect of these antibodies was also demonstrated on human colon cancer cell lines LS174T and HT29-MTX but not on Caco-2 cells. Although immunoblotting showed similar binding patterns of all the antibodies on HT29 cell membrane extracts, there was little correlation between cell surface binding assessed by immunofluorescence and proliferative response, and internalization of the biotinylated antibody TF5 was demonstrated by confocal microscopy. Our results provide further evidence that cell surface glycoproteins which express TF antigen may play an important role in the regulation of cell proliferation and also suggest that human anti-TF antibodies may have proliferative effects on cells which express TF antigen.

Antibodies↗
PubMed1997

Human monoclonal antibodies specific for the tumour associated Thomsen-Friedenreich antigen.

Five hybridomas producing human monoclonal antibodies (MAbs) of IgA and IgM isotypes reacting with the tumour associated TF antigen were generated after in vitro immunisation or antigen specific isolation of normal peripheral blood B cells using asialoglycophorin, a TF containing antigen. All 5 antibodies produced by the hybridomas bound strongly to asialoglycophorin and to synthetic glycoprotein containing the TF-epitope, with preference to the beta form (Galb1-3GalNAc-beta-O-CETE-BSA) as compared to the alpha form (Galbl-3GalNAc-alpha-O-APE-HSA) in ELISA. Flow cytometry analysis revealed binding to carcinoma cell lines of different origin such as breast, colon, pancreas, ovary, bladder, lung and, in addition, to some tumour cell lines of haematopoietic origin. Immunohistochemical analysis of tumour tissues revealed staining patterns typical for mucins, and the antibodies were found to bind to glycoproteins among the MUC-1 positive high m.w. fraction shed from a TF antigen positive ovarian carcinoma cell line.

Animals↗
PubMed1997

Coxarthrosis and farm work: a case-referent study.

The purpose of this case-referent study was to analyze the association between coxarthrosis and occupation. The study was performed in a Swedish agricultural county and comprised 269 cases of radiologically verified arthrosis of osteoarthritis (< 3 mm joint space) that were compared to 538 randomly selected controls in the same region, matched for age, sex, and place of residence. Farmers and agricultural workers showed an increased risk of coxarthrosis and the observed risk increased with increasing number of years of farming. Tractor driving and milking were associated with coxarthrosis, whereas no association with other types of machine work could be demonstrated. An association between coxarthrosis and heavy physical work before the age of 16 years was also observed. The results give only limited information on the external causes of coxarthrosis, however. More detailed studies of groups of individuals with coxarthrosis in order to obtain more information about contributing and underlying factors would therefore be valuable.

Adult↗
PubMed1997

A dose-response study comparing suppression of plasma cortisol induced by fluticasone propionate from Diskhaler and budesonide from Turbuhaler.

OBJECTIVE: To compare the systemic potency of inhaled fluticasone propionate delivered via Diskhaler (FP-DH), and inhaled budesonide delivered via Turbuhaler (BUD-TBH) over the clinically recommended dose range using plasma cortisol suppression as a marker for systemic activity. METHODS: The systemic potency was examined in a dose-response study in 81 healthy male volunteers. The study was of an open, randomized, parallel-group (four groups) design, where two treatments were given in crossover fashion within each group. FP-DH and BUD-TBH were given b.i.d. for 7 days (14 doses): 100 and 100 micrograms (group 1); 200 and 200 micrograms (group 2); 500 and 400 micrograms (group 3); 1000 and 800 micrograms (group 4). There was a washout period of 7 days within each treatment group. All doses were administered at 08:00 and 20:00 hours. Multiple plasma cortisol samples were taken every 2 h over 24-h periods prior to randomization (baseline) and during steady state (i.e., the last two dosing intervals). Cortisol suppression was determined by comparing average plasma concentrations of cortisol before and during treatment. Dose-response curves for cortisol suppression were analyzed using multivariate non-linear regression (Hill modeling). RESULTS: Multiple dosing for 7 days with FP-DH and BUD-TBH resulted in dose-dependent cortisol suppression by both drugs, most pronounced at the two highest dose levels. FP-DH-induced suppression was 41% at 500 micrograms and 86% at 1000 micrograms b.i.d., while that induced by BUD-TBH was 19% at 400 micrograms and 47% at 800 micrograms b.i.d. Statistically significant differences were found when comparing the two steroids at these two dose levels. Doses producing 50% of maximum suppression (ED50) were estimated at 833 micrograms b.i.d. for BUD-TBH and 479 micrograms b.i.d. for FP-DH. This gave an estimated relative cortisol suppression over the dose range of 1.74:1 (FP-DH:BUD-TBH). ED50 values, estimated from cortisol concentrations at 08:00 hours (12 h after the last dose), were 1212 micrograms b.i.d. for BUD-TBH and 527 micrograms b.i.d. for FP-DH giving a relative cortisol suppression of 2.30:1 (FP-DH:BUD-TBH). Fourteen subjects on the highest FP-DH dose and 3 at the next highest dose had morning plasma cortisol levels below the lower reference limit. No subject taking budesonide, however, had morning plasma cortisol levels below the reference limit. Analysis of the time for return to pretreatment baseline levels showed that cortisol suppression, 12-24 h after the last dose, was statistically significant compared with the baseline for the highest dose of FP-DH but not for any of the BUD-TBH doses. CONCLUSIONS: The results of the present study show that FP-DH suppresses plasma cortisol more than BUD-TBH on a equivalent basis with regard to both magnitude and duration.

Administration, Inhalation↗
PubMed1997

Moxonidine and cognitive function: interactions with moclobemide and lorazepam.

OBJECTIVE: Moxonidine represents a new generation of centrally acting antihypertensive drugs. It binds to I1-imidazoline receptors and exerts its antihypertensive activity through a reduction in systemic vascular resistance, while cardiac output remains unchanged or even increases slightly. Moxonidine is prescribed for the treatment of mild to moderate hypertension. Typical doses are 0.4 to 2.0 mg given as one dose in the morning or as divided doses in the morning and evening. METHODS: The effects of moxonidine 0.4 mg once daily in combination with moclobemide or lorazepam were investigated in two, double-blind, randomised, placebo-controlled, two-way crossover studies in a total of 48 healthy volunteers. Safety assessments were made in each study and included pre- and post-study measurement of blood pressure, heart rate, ECG, haematology, blood biochemistry, and urinalysis, and recording of adverse events. RESULTS: In the first study, moxonidine alone was found to produce small but statistically significant impairments of vigilance detection speed at 4 h and 6 h. Lowering of subjective alertness was also observed. Repeat dosing with moxonidine produced an impairment of memory scanning performance. These findings were not reproduced in the second study, in which moxonidine alone produced an improvement in immediate word recall at 4 h and 6 h. No interactions were observed when moxonidine was co-administered with moclobemide. Moxonidine, when co-administered with lorazepam, produced interactions with three tasks requiring high levels of attention: choice, simple reaction time and digit vigilance performance; memory tasks; immediate word recall, delayed word recall accuracy; and visual tracking. A total of 47 adverse events were reported in study 1. Moxonidine produced a slight decrease of systolic and diastolic blood pressure. In study 2, a total of 55 adverse events were reported. In both trials, the most frequently reported events were tiredness and dryness of mouth, the latter occurring only under the moxonidine treatment. There were no clinically relevant changes observed in blood pressure, pulse rate, and laboratory tests in either study, nor was there any evidence of any interaction between moxonidine and either moclobemide or lorazepam. CONCLUSION: Moxonidine was found to be safe and well tolerated in healthy volunteers. However, the impairments on attentional tasks were greater when moxonidine was co-administered with lorazepam 1 mg. These effects should be considered when moxonidine is codosed with lorazepam, although they were smaller than would have been produced by a single dose of lorazepam 2 mg.

Adolescent↗
PubMed1997

Tissue distribution of transplanted fetal liver cells in the human fetal recipient.

OBJECTIVE: Our purpose was to study the tissue distribution and concentrations of transplanted fetal liver cells in the human fetus. STUDY DESIGN: Radiolabeled indium 111 fetal liver cells were injected in vivo under ultrasonographic guidance into 10 normal fetuses (13 to 17 weeks of gestation) before a prostaglandin abortion. Six fetuses were injected intraperitoneally and four intracardially. Another two fetuses serving as controls were injected with indium-labeled maternal plasma. The fetuses were all alive, at least until 6 hours before expulsion. After expulsion the fetuses were dissected, and radioactivity was measured in various fetal tissues. Results for each tissue were expressed as percentages of the total injected dose. RESULTS: Significantly greater uptake of fetal liver cells in the liver, spleen, thymus, kidney, lung, and placenta was obtained with intracardiac than with intraperitoneal injection. Skeletal uptake did not differ in relation to mode of administration. With intracardiac injection uptake was greater in such parenchymal organs as the liver, spleen, and thymus (4.9%, 4.0%, and 3.9%, respectively). Uptake in the rib, clavicle, humerus, and sternum was 2.7%, 1.8%, 2.1%, and 1.1%, respectively. Placental uptake was 0.1%. The intracardiac route yielded a higher concentration of cells in different fetal organs than did injection of only radiolabeled maternal plasma, suggesting an active uptake of cells in different fetal hematopoietic organs. CONCLUSION: The mode of administration of fetal liver cells seems to be a major determinant of donor cell concentration in the transplanted human fetus and may be a significant determinant of the rate of successful engraftment.

Cell Movement↗
PubMed1997

National adaptations of the ICD rules for classification--a problem in the evaluation of cause-of-death trends.

In 1981, the registration routines of the Swedish cause-of-death register were adjusted. The aim of this study was to assess what influence these changes in registration practice might have had on the cause-of-death trends after 1981. The Eighth Revision of the International Classification of Diseases (ICD-8) was used throughout the study period (1976-1985). Significant changes in the registered number of cases were found in 13 of the 18 diagnostic groups scrutinized. Four main types of outcomes were observed: (a) the number of underlying causes increased while the number of contributing causes decreased or vice versa; (b) the number of both underlying and contributory causes changed in the same direction, due to the transfer of a diagnostic group from one ICD category to another; (c) the number of both underlying and contributory causes changed in the same direction, but not due to the transfer of a diagnostic group; or (d) the number of either underlying or contributory causes changed, but not both. In general, the altered registration practice led to more conditions that are often considered as terminal complications to other diseases being registered as the underlying cause of death. While most of the 1981 instructions meant a more literal application of the ICD-8, those concerning cardiac valvular diseases deviated substantially from it. We conclude that (a) important changes in registration practice may occur at any point in time, and not only in connection with the implementation of a new version of the ICD; and (b) national adaptations of the ICD coding instructions may amount to a reversal of the instructions included in the ICD manuals. These findings must be considered when comparing cause-of-death statistics from different countries, and both underlying and contributing cause-of-death statistics should be considered in such analyses of cause-of-death trends.

Cause of Death↗
PubMed1997

Clinical safety of enamel matrix derivative (EMDOGAIN) in the treatment of periodontal defects.

The aim of the present clinical trial was to test tolerability during 2 treatments with EMDOGAIN in a large number of patients. An open, controlled study design in 10 Swedish specialist clinics was chosen, with a test group of 107 patients treated with EMDOGAIN in connection with periodontal surgery at 2 surgical test sites per patient. The procedures were performed 2 to 6 weeks apart on one-rooted teeth with at least 4 mm deep intraosseous lesions. A control group of 33 patients underwent flap surgery without EMDOGAIN at 1 comparable site. In total, 214 test and 33 control surgeries were performed. Serum samples were obtained from test patients for analysis of total and specific antibody levels. 10 of the patients had samples taken before and after the first surgery, 56 other samples were taken after one treatment with EMDOGAIN, and 63 after 2 treatments. None of the samples, not even from allergy-prone patients after 2 treatments, indicated deviations from established baseline ranges. This indicates that the immunogenic potential of EMDOGAIN is extremely low when applied in conjunction with periodontal surgery. Comparison between the test and control groups demonstrated the same type and frequency of postsurgical experiences, i.e., reactions caused by the surgical procedure itself. Clinical probing and radiographic evaluation was performed at baseline and 8 months postsurgery. About half of the patients (44 test and 21 control) were also evaluated after 3 years. There was a significant difference between the test and control results at 8 months postsurgery, and this difference had increased further at the 3 year follow-up. The 2.5-3 mm increase in attachment and bone level after treatment with EMDOGAIN was of the same magnitude as seen in the studies with split-mouth design aiming for test of effectiveness of EMDOGAIN.

Adult↗
PubMed1997

[ELISA of IgM antibodies to Thomsen-Friedenreich (TF) hapten in cancer diagnostics: comparison of data obtained with four TF-glycoconjugates].

The level of IgM antibodies to the Thomsen-Friedenreich hapten (TF) relative to the total IgM level in the blood sera of gastric and breast carcinoma patients and healthy persons was determined using enzyme-linked immunosorbent assay. The following TF glycoconjugates were tested: TF-polyacrylamide (PAA)(with 10 mol.% of TF hapten Gal beta 1-3GalNAc alpha 1-O(CH2)3NH per number of monomeric units in the polyacrylamide), TF-human serum albumin (HSA)(Gal beta 1-3GalNAc alpha 1-O-p-C6H4-HSA containing approximately 15 carbohydrate residues per HSA molecule), asialo-kappa-caseinoglycopeptide, and asialoglycophorin. The total IgM level was determined using antibodies to the mu-chain of human IgM. The statistically significant difference between cancer patients and healthy donors was revealed with two conjugates: TF-PAA and TF-HSA. In the case of TF-PPA, the sensitivity of the assay was 75-83%, and the specificity was 77%. Thus, TF-PAA is the most suitable conjugate for measuring the level of serum anti-TF-IgM antibodies.

Acrylic Resins↗
PubMed1996

Resistance to V3-directed neutralization caused by an N-linked oligosaccharide depends on the quaternary structure of the HIV-1 envelope oligomer.

A conserved N-glycan present within the V3 loop of gp120 modulates the sensitivity to neutralization by antibodies directed to the V3 loop. A glycan-deficient mutant of HIVLAI, designated HIVA308, displayed a 100-fold increase in sensitivity to neutralization by anti-V3 MAb NEA-9205 compared to wild-type HIVLAI. This difference in sensitivity was not caused by an alteration of the antibody binding site itself, as NEA-9205 had equal affinity for both wild-type and mutant monomeric gp120. In contrast, virion-associated wild-type gp120 was immunoprecipitated less efficiently with NEA-9205 than virion-associated mutant gp120. This difference was completely abrogated, if immunoprecipitation were carried out in the presence of detergent. Furthermore, treatment of virion preparations with detergent exposed the C-terminal D7324 epitope, which is inaccessible on virion-associated gp120 but readily accessible on monomeric, soluble gp120. Finally, both wild-type and mutant monomeric, soluble gp120 were precipitated equally efficiently by NEA-9205 in the absence of detergent. Thus, the NEA-9205 epitope was readily accessible on monomeric gp120 regardless of the presence of the 306N-glycan, and inaccessibility of the NEA-9205 epitope imparted by the 306N-glycan was observed only on the intact envelope oligomer.

Animals↗