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Biomedical subjects

B Olsson

Publications and source records attributed to B Olsson.

At least 55 records · Page 3Linked to original sources

The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes.

The peptide FA-LL-37, previously termed FALL-39, was originally predicted from on ORF of a cDNA clone isolated from a human bone marrow library. This peptide was synthesized and found to have antibacterial activity. We have now characterized and sequenced the complete gene for FA-LL-37, termed FALL39. It is a compact gene of 1963 bp with four exons. Exons 1-3 code for a signal sequence and the cathelin region. Exon 4 contains the information for the mature antibacterial peptide. Our results indicate that FALL39 is the only member of the cathelin gene family present in the human genome. Potential binding sites for acute-phase-response factors are identified in the promoter and in intron 2. A possible role for the cytokine interleukin-6 in the regulation of FALL 39 is discussed. Anti-(FA-LL-37) IgG located the peptide in granulocytes and we isolated the mature peptide from these cells after degranulation. Structural analysis determined the mature peptide to be LL-37. To obtain LL-37 for antibacterial assays, synthetic FA-LL-37 was degraded with dipeptidyl-peptidase I. This analysis showed that mature LL-37 is a potent antibacterial peptide.

Amino Acid Sequence↗

NK-lysin, structure and function of a novel effector molecule of porcine T and NK cells.

NK-lysin (NKL), a 78-residue antimicrobial peptide, was isolated from pig small intestine. Standard methods identified the peptide as basic, with six half-cystine residues in three intrachain disulphide bonds. The sequence showed 33% identity with a part of a putative gene product (NKG5) from activated T and NK cells, NK-lysin showed antibacterial activity against Escherichia coli and Bacillus megaterium and marked lytic activity against YAC-1, a NK sensitive tumour cell line, while sheep red blood cells were unaffected. The cDNA clone corresponding to NK-lysin has been characterized. We have also analyzed the cell and tissue specific expression and the induction of the gene. A lymphocyte fraction enriched in T and NK cells, stimulated by human interleukin-2 (IL-2), showed a 30-fold increase of the NKL transcript. NK-lysin specific mRNA is also detectable in spleen, bone marrow and colon. Immunostaining showed NKL to be present in different types of lymphocytes. Our results strongly suggest that NK-lysin is involved in the inducible cytotoxicity of T and NK cells.

Animals↗

The childbirth experience: a study of 295 new mothers.

BACKGROUND: The childbirth experience is multidimensional, and therefore difficult to describe and explain. Studies of it have produced inconsistent findings, and the phenomenon is often confused with satisfaction with the care provided. This study aimed to clarify different aspects of the birth experience, and to identify factors that could explain the variation in women's overall assessment of it. METHODS: All Swedish-speaking women in a large city who gave birth during a two-week period in 1994 were given a questionnaire one day after the birth, and 295 (91%) of the questionnaires were returned. Information about the labor process and medical interventions was collected from hospital records. RESULTS: Women usually experienced severe pain and various degrees of anxiety, and most were seized with panic for a short time or some part of their labor. Despite these negative feelings, most women felt greatly involved in the birth process, were satisfied with their own achievement, and thought they had coped better than expected. The overall experience was assessed as positive by 77 percent of women and negative by 10 percent. No statistical difference was observed between primiparas and multiparas in total birth experience, and few differences in the specific aspects of the birth. Of the 38 variables tested in regression analysis, the six that contributed to explaining women's overall birth experience were support from the midwife (sensitivity to needs), duration of labor, pain, expectations of the birth, involvement and participation in the birth process, and surgical procedures (emergency cesarean section, vacuum extraction, forceps, episiotomy). CONCLUSIONS: The study showed that negative and positive feelings can coexist, thus confirming the multidimensional character of the birth experience. Women's assessment of their childbirth is influenced by both physical and psychosocial factors, highlighting the importance of a comprehensive approach to care in labor.

Adult↗

NK-lysin, a novel effector peptide of cytotoxic T and NK cells. Structure and cDNA cloning of the porcine form, induction by interleukin 2, antibacterial and antitumour activity.

A 78 residue antimicrobial, basic peptide, NK-lysin, with three intrachain disulfide bonds was purified from pig small intestine and characterized. A corresponding clone was isolated from a porcine bone marrow cDNA library. The 780 bp DNA sequence had a reading frame of 129 amino acids which corresponded to NK-lysin. The clone was used to show that stimulation with human interleukin-2 induced synthesis of NK-lysin-specific mRNA in a lymphocyte fraction enriched for T and NK cells. Lower levels of mRNA were detected in tissues known to contain T and NK cells, such as small intestine, spleen and colon. Interleukin-2 also induced both proliferation of the lymphocyte fraction and cytolytic function in these cells. Immunostaining showed that NK-lysin was present in cells positive for CD8, CD2 and CD4. NK-lysin showed high anti-bacterial activity against Escherichia coli and Bacillus megaterium and moderate activity against Acinetobacter calcoaceticus and Streptococcus pyogenes. The peptide showed a marked lytic activity against an NK-sensitive mouse tumour cell line, YAC-1, but it did not lyse red blood cells. The amino acid sequence of NK-lysin exhibits 33% identity with a putative human preproprotein, NKG5, of unknown function but derived from a cDNA clone of activated NK cells. We suggest that NK-lysin is a new effector molecule of cytotoxic T and NK cells.

Amino Acid Sequence↗

Aerosol particle generation from dry powder inhalers: can they equal pressurized metered dose inhalers?

In comparison with pressurized metered dose inhalers (pMDIs), dry powder inhalers (DPIs) emit a semi-stable aerosol cloud and are inspiratory flow actuated and inspiratory flow driven. In vitro studies show that different DPIs vary in their efficiency as delivery systems of fine drug particles (aerodynamic diameter < 5 microns). The efficiency of DPIs may vary according to the inspiratory force used to generate the aerosol. In comparison with other DPIs, Turbuhaler has been shown to be an efficient fine particle generator at weak, moderate and strong inspiratory forces. Deposition studies using human throat casts have shown that the throat has a minor influence on the deposition of drugs delivered from DPIs, whereas the throat has a major influence on the deposition of drug delivered from pMDIs. The fine particle dose able to penetrate the human throat casts was considerably higher for budesonide Turbuhaler than for budesonide pMDI, whereas for fluticasone propionate the fine particle dose was considerably higher from the pMDI than from Diskhaler. Thus, whether the fine particle dose and the deposition pattern of a drug generated from DPIs can equal that generated from pMDIs depends on the drug, the formulation and the patient.

Adult↗

Doxycycline carrageenate--an improved formulation providing more reliable absorption and plasma concentrations at high gastric pH than doxycycline monohydrate.

The effect of increased gastric pH (obtained by pre-treatment with omeprazole) on the bioavailability of doxycycline monohydrate and doxycycline carrageenate has been investigated in 24 healthy volunteers, using an open, randomised, four-treatment, four-period, cross-over, 2 x 2 factorial design. Each subject received a single dose of 100 mg of each of the doxycycline formulations with and without pre-treatment with omeprazole (40 mg daily for 7 days). The two formulations were bioequivalent (rate and extent) during fasting without omeprazole pre-treatment, whereas after omeprazole, the monohydrate showed a highly significant decrease in bioavailability (38% for AUC and 45% for Cmax) compared to the carrageenate formulation, which was not affected by prior administration of omeprazole. Many of the subjects did not reach a therapeutic plasma level of doxycycline during the combination of omeprazole and doxycycline monohydrate, and most adverse events (mainly gastrointestinal) were reported after this combination. As large populations of patients have a high gastric pH due to frequent use of H2-blockers, proton pump inhibitors and antacids, as well as to physiological achlorhydria, the decreased absorption of doxycycline monohydrate may well have a clinical impact, for example when the patients are treated with tetracyclines for an infection.

Adult↗

Critical aspects of the function of inspiratory flow driven inhalers.

Powder inhalers rely on the patient's inspiratory flow for delivery and aerosolization of the medicament. Different inhalers offer different resistances to inspiration through the device. The flow rate attained by a patient depends on the effort expended and on the air flow resistance of the device; flow rate is thus a device-dependent variable. A comparison between powder inhalers should therefore take their air flow resistances into account. An empirical relation between the peak inspiratory flow rate through a device and the flow resistance of the device has been developed using results from healthy subjects and verified to a limited extent using data from asthmatic patients. The flow resistance was measured as the pressure drop at a fixed flow rate. The empirical relation can be used to predict the change in peak inspiratory flow rate resulting from a change in flow resistance. Matching flow rates, representing equal inspiratory efforts, may thus be calculated for different inhalation devices.

Aerosols↗

Cerebral lesions on magnetic resonance imaging, heart disease, and vascular risk factors in subjects without stroke. A population-based study.

BACKGROUND AND PURPOSE: To assess the prevalence of asymptomatic abnormalities on magnetic resonance imaging of the brain and their possible relation to hypertension, heart disease, and carotid artery disease, we studied 77 randomly selected subjects (mean age, 65.1 years; range, 36 to 95 years) with no history of focal brain lesions. METHODS: The study protocol included magnetic resonance imaging of the brain, transthoracic and transesophageal echocardiography, ultrasonography of the carotid arteries, and electrocardiographic recording. Deep and periventricular white matter hyperintensities on magnetic resonance imaging were assessed both separately and together. RESULTS: On magnetic resonance imaging of the brain 62.3% (95% confidence interval [CI], 51.5% to 73.2%) of the subjects had white matter hyperintensities. These abnormalities increased significantly with age (chi 2 test; P = .0001), from 13.6% (95% CI, 0% to 28.0%) of subjects aged younger than 55 years to 85.2% (95% CI, 71.8% to 98.6%) of subjects aged 75 years or older. Six subjects had deep gray matter hyperintensities localized in the basal ganglia, and one had a cerebellar infarction. Stepwise logistic regression analysis identified age and a history of heart disease (but not echocardiographic findings) to be independently associated with deep and periventricular white matter hyperintensities. Hypertension was only independently associated with periventricular white matter hyperintensities. Of the 68 subjects examined with both transthoracic and transesophageal echocardiography, potential cardioembolic sources were detected in 38.2% (95% CI, 26.7% to 49.8%) of the subjects with transthoracic echocardiography and in 47.1% (95% CI, 35.2% to 58.9%) of those with transthoracic and transesophageal echocardiography combined. In subjects aged 75 years or older, a possible cardiac embolic source was detected in 64.0% on transthoracic echocardiography and in 72.0% on transthoracic and transesophageal echocardiography combined, compared with 5.3% and 15.8%, respectively, in subjects aged younger than 55 years. CONCLUSIONS: White matter hyperintensities and potential cardioembolic sources are frequently present in asymptomatic individuals, stressing the need for age-matched control subjects in studies of patients with stroke or dementia.

Adult↗