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Biomedical subjects

A Johansson

Publications and source records attributed to A Johansson.

At least 73 records · Page 4Linked to original sources
PubMed2002

Lack of lipoprotein-dependent effects on the cytotoxic interactions of Actinobacillus actinomycetemcomitans leukotoxin with human neutrophils.

A high odds ratio has been reported for hyperlipidemia and periodontal diseases in humans, and the severity of periodontitis seems to correlate with the hyperlipidemic status of the patients. Early studies indicated that the lipoprotein-containing fraction of the serum enhances the leukotoxic activity of the periodontopathogen Actinobacillus actinomycetemcomitans against human polymorphonuclear leukocytes (PMNL). The protease inhibitors of normal serum account for this enhancement, while delipidated serum has no effect on the leukotoxin-dependent PMNL cytolysis. No information exists for the effect of serum lipoproteins or hyperlipidemic serum. The aim of this study was to evaluate the role of serum lipoproteins in the interaction of the leukotoxin of A. actinomycetemcomitans with human PMNL. Purified leukotoxin was mixed with human PMNL prepared from venous blood of healthy subjects and various varying amounts of hyperlipidemic or delipidated serum, or purified serum lipoproteins. The cytolytic activity of leukotoxin was determined by activity of the cytosol enzyme lactate dehydrogenase released from injured PMNL. The degranulating activity of the toxin was measured through the release of the granule components elastase and lactoferrin. Normal human serum without leukotoxin-neutralizing antibodies caused a 4-fold enhancement of the leukotoxic activity when present at concentrations of 5-10% in the reaction mixture. Serum lipoproteins had no effect when added at concentrations that occur normally in serum. At high concentrations, purified low density and very low-density lipoproteins increased the leukotoxicity of the mixture. Nevertheless, hyperlipidemic serum prepared from a normal serum by the addition of autologous lipoproteins had no influence on the leukotoxin-caused cytolysis compared to the normal serum. Pre-incubation of PMNL for 1 h in hyperlipidemic or delipidated serum had no effect on the leukotoxin-induced degranulation of PMNL. The results indicate that the cytotoxic interactions of A. actinomycetemcomitans leukotoxin against human PMNL are not influenced by the presence of serum lipoproteins.

Aggregatibacter actinomycetemcomitans↗
PubMed2002

Release and activation of matrix metalloproteinase 8 from human neutrophils triggered by the leukotoxin of Actinobacillus actinomycetemcomitans.

Matrix metalloproteinase 8 (MMP 8) degrades type I collagen and may be involved in the pathogenesis of periodontitis. Latent MMP 8 is stored in neutrophil granules and can be activated when released extracellularly. The periodontitis-associated bacterium Actinobacillus actinomycetemcomitans produces an RTX-toxin, leukotoxin, that degranulates and lyses human neutrophils. This study deals with the ability of leukotoxic A. actinomycetemcomitans to trigger the release and activation of MMP 8. Whole bacteria of three A. actinomycetemcomitans strains or leukotoxin purified from the highly toxic strain HK 1519 were incubated with human neutrophils. The extracellularly released latent and active forms of MMP 8 were detected by an immunoblot technique using specific antibodies against the protease. The activity of MMP 8 was determined by a collagen degradation assay. All strains induced release and activation of MMP 8. The effect was more pronounced under aerobic than anaerobic conditions and correlated with the leukotoxicity of the strains. Pure leukotoxin also induced MMP 8 release and activation in a concentration-dependent manner. Under aerobic conditions, oxidising substances formed by the neutrophils contributed to the rapid activation of the latent enzyme. Upon anaerobic incubation, the activation was slow and mainly caused by other proteases released during neutrophil degranulation. The activation was totally abolished in the presence of serum, probably due to the serum-protease inhibitors. Compared to the calcium ionophore A 23187, a well-known stimulus of neutrophil degranulation, leukotoxin was a more powerful inducer of MMP 8 release, since it triggered the process at a 1000-fold lower concentration. The present findings reveal a specific mechanism that can be induced by A. actinomycetemcomitans leukotoxin and which may contribute to the degradation of periodontal tissues under certain conditions.

Aerobiosis↗
PubMed2002

Testosterone and diurnal rhythmicity of leptin, TNF-alpha and TNF-II receptor in insulin-resistant myotonic dystrophy patients.

OBJECTIVE: To investigate the leptin and TNF systems in relation to testosterone in insulin resistant myotonic dystrophy (DM1) subjects. DESIGN AND SUBJECTS: Fasting morning samples and diurnal sampling during 24 h. Forty-two DM1 subjects (20 women and 22 men; age 41.5 (28.5-58.7) y, body mass index (BMI) 23.3 (18.6-29.2) kg/m(2); median and 10th and 90th percentile, respectively). Fifty healthy volunteers (23 women and 27 men; age 42 (27.0-56.9) y, BMI 24.0 (20.7-29.7) kg/m(2)). Nine men with DM1 and nine healthy men participated in diurnal sampling. MEASUREMENTS: Body composition was measured by bioelectric impedance analysis. Circulating levels of leptin, TNF-alpha, TNFR-II, insulin, testosterone and lipids were measured. The number of CTG triplet repeats was analysed. RESULTS: Basal as well as median 24 h levels of leptin and TNFR-II were significantly increased in DM1 patients, independent of body fat mass. This was associated with higher insulin and lower testosterone levels in DM1 patients. The genetic defect was related to leptin and TNFR-II levels in DM1 patients. CONCLUSION: Hyperleptinemia in DM1 is clearly linked to the concomitant hypogonadism. The genetic defect may directly or indirectly contribute to increased leptin levels. Increased exposure of cytokines may contribute to insulin resistance and other hormonal disturbances in DM1.

Adult↗
PubMed2002

Capsaicin inhalation test for identification of sensory hyperreactivity.

BACKGROUND: Patients with upper and lower airway symptoms and with pronounced sensitivity to chemical odours, such as perfumes, flower scents and tobacco smoke, have been suggested to have sensory hyperreactivity (SHR). The symptoms have been difficult to identify with physiological measurements and the effects of various medications are doubtful. However, these patients have been found to be more sensitive to inhalation of capsaicin than healthy people. The aim of this study was to establish limit values with the capsaicin inhalation test in patients with SHR. METHODS: Ninety-five consecutive patients with upper and lower airway problems, who were admitted for allergy testing, underwent a capsaicin inhalation test with three different concentrations. The number of coughs was registered during each challenge. Score systems were used for symptoms and influence on social life of sensitivity to odours. In relation to scored symptoms, the patients were grouped as SHR or not, and compared with 73 healthy controls. RESULTS: All patients and controls coughed on capsaicin in a dose-dependent manner. Symptom score of odour sensitivity in patients was positively correlated to the response of the test. Out of 95 patients, 15 (16%) were scored to SHR. Patients with SHR reacted more to the capsaicin inhalation test than the other patients and the healthy controls. The limit values for a positive capsaicin inhalation test for the SHR were determined to be 10, 35 and 55 coughs at 0.4, 2.0 and 10 microM capsaicin, respectively. CONCLUSION: The capsaicin inhalation test well reflects the degree of airway sensitivity to chemicals and to what extent the social life is influenced. The cut-off values of the test can distinguish patients with pronounced sensitivity to odours.

Administration, Inhalation↗
PubMed2002

Non-viral mediated gene transfer of porphobilinogen deaminase into mammalian cells.

Acute intermittent porphyria (AIP) is an inborn error of heme synthesis in which the third enzyme, porphobilinogen deaminase (PBGD), is deficient. The disease is characterized by recurrent attacks of acute abdominal pain often accompanied by neuropsychiatric symptoms. Current therapeutic treatment with heme is only palliative and no curative alternative exists. The present report describes the first step towards a gene therapy treatment for AIP. Mouse cDNA encoding the PBGD enzyme was cloned and four vectors containing the full-length mouse and human cDNA of the housekeeping and erythroid PBGD isoforms under the control of a cytomegalovirus promoter were constructed. The vectors, condensed to polyethylenimine, were successfully transfected to NIH 3T3 and HeLa cells as determined by enzymatic activity measurements. Thus, the PBGD activity was increased 3-10 times in NIH 3T3 cells and 95-240 times in HeLa cells. The expression was shown to be dose and time dependent, with the highest level of activity observed in HeLa cells after 72 h posttransfection. Non-viral gene transfer was also undertaken in PBGD-deficient fibroblasts established from an AIP patient. Complete normalization of the PBGD activity was accomplished after the addition of 2.5 microg DNA per well. Further addition of DNA increased the PBGD activity up to threefold the normal value. The study documents a successful gene transfer and a high degree of PBGD expression in different cell-lines, indicating a potential for future gene therapy in AIP.

3T3 Cells↗
PubMed2002

Apoptosis in HeLa Hep2 cells is induced by low-dose, low-dose-rate radiation.

Radioimmunotherapy with radiolabeled antibodies may cause inhibition of the growth of epithelial tumors, despite low total radiation doses and comparatively low radiosensitivity of epithelial tumor cells. The induction of apoptosis by low-dose radiation, such as delivered in radioimmunotherapy, was investigated in vitro in human HeLa Hep2 carcinoma cells. The cultured cells were exposed to defined radiation doses from a (60)Co radiation therapy source. The radiation source delivered 0.80 +/- 0.032 (mean +/- SD) Gy/min and the cells were given total doses of 1, 2, 5, 10 and 15 Gy. Using fluorescein-labeled Annexin V, followed by flow cytometry and DNA ladder analysis, apoptotic cells were detected and quantified. Radiation doses below 2 Gy did not cause any significant increase in apoptosis. Compared to control cells, apoptosis was pronounced after 5-10 Gy irradiation and was correlated to the radiation dose, with up to 42 +/- 3.5% of the cells examined displaying apoptosis. Clonogenic assays confirmed significantly decreased viability of the cells in the interval 2 to 10 Gy with low-dose-rate radiation, 60 +/- 2% compared to 2 +/- 2%. Lethal effects on the tumor cells were also evaluated by an assay of the cytotoxic effects of the release of (51)Cr. Significant cytotoxicity, with up to 64 +/- 6% dead cells, was observed at 5 Gy. Similar results were obtained when the dose rate was reduced to 0.072 +/- 0.003 Gy/min (mean +/- SD). In the case of the (137)Cs source, the dose rate could be reduced to 0.045 Gy/h, a level comparable to radioimmunotherapy, which induced significant apoptosis, and was most pronounced at 72-168 h postirradiation. It can be concluded that in vitro low-dose and low-dose-rate radiation induces apoptosis in epithelial HeLa Hep2 cells and thus may explain a mechanism by which pronounced inhibition of growth of HeLa Hep2 tumors at doses used in radioimmunotherapy has been obtained previously.

Annexin A5↗
PubMed2002

Comparative peptidomics of the endocrine pancreas: islet hormones from the clawed frog Xenopus laevis and the red-bellied newt Cynops pyrrhogaster.

Electrospray mass spectrometry coupled with reverse-phase HPLC was used to identify peptides in the molecular mass range 3000-6000 Da in extracts of the pancreata of the clawed frog Xenopus laevis (Anura: Pipidae) and the red-bellied newt Cynops pyrrhogaster (Caudata: Salamandridae). Amino acid sequences of insulins, peptides derived from the post-translational processing of proglucagons and pancreatic polypeptide were determined by automated Edman degradation. Three molecular forms of insulin were isolated from the tetraploid organism X. laevis that represent insulin-1 and insulin-2, as deduced from the nucleotide sequences of previously characterized cDNAs, and a third form which differed from insulin-2 by the single amino acid substitution Asp(21)-->Glu in the B-chain. The amino acid sequence of Xenopus preproglucagons (genes 1 and 2 ) may be deduced from the nucleotide sequences of cDNAs but the pathways of post-translation processing of the precursors are not known. Two molecular forms of glucagon with 36 amino acids, derived from genes 1 and 2 and representing glucagon-29 extended from its C terminus by different heptapeptides, and five molecular forms of glucagon-like peptide 1 (GLP-1) were isolated. The GLPs represent proglucagon-(77-113), -(122-158) and -(160-191) from gene 1, and proglucagon-(77-113) and -(160-191) from gene 2. A single molecular form of insulin, glucagon-36, a C-terminally alpha-amidated GLP-1 with 30 amino acid residues, a 33 amino acid residue GLP-2 and pancreatic polypeptide were isolated from the pancreatic extract of the diploid organism C. pyrrhogaster. This study has illustrated the power of electrospray mass spectrometry for the rapid and reliable identification of peptides in chromatographic fractions without the need to use radioimmunoassay, radioreceptor assay or bioassay.

Amino Acid Sequence↗
PubMed2001

Quantitative analysis of inhomogeneity in ventilation SPET.

The aim of this study was to evaluate a method for quantification of inhomogeneity in ventilation single-photon emission tomography (SPET). Nine emphysematous patients, nine life-long non-smokers and nine smokers were included in the study. The SPET investigation was performed after 50 MBq (99m)Tc-Technegas had been inhaled by each subject in the supine position. A single-head gamma camera, equipped with a general-purpose parallel-hole collimator using 64 projections (20 s each) over 360 degrees, was used. Data were acquired in 128x128 matrices. Attenuation correction was applied based upon computed tomography (CT) density maps. Lung regions of interest were delineated manually on CT images and then positioned on SPET images. Several attenuation-corrected transaxial SPET slices (thickness 1 cm, spacing 3.5 cm) were reconstructed. Each SPET slice was divided into several 2x2x1 cm(3) elements. Inhomogeneity was assessed by the coefficient of variation (CV) of the pixel counts within these elements (micro-level) and the CV of the total counts of the elements (macro-level). Micro-level CVs in non-smokers varied between 1% and 41%, whereas they were dispersed over a wide range (1%-600%) in emphysematous patients. In seven smokers, the frequency distribution of micro-level CVs was within the normal range, whereas in the other two smokers the values were between the normal range and the range in emphysematous patients. The pooled mean values of micro-level CVs and macro-level CVs in each subject clearly separated the patients from the others. Parametric images of micro-level CV indicated the localisation and severity of ventilation inhomogeneity. We conclude that the present method enables quantification and localisation of regional inhomogeneity in ventilation SPET images.

Adult↗
PubMed2001

Homo- and heterocomplexes of sodium and lithium amides--structures in solution.

Addition of the chiral amine (S)-methyl(1-phenyl-2-pyrrolidinoethyl)[15N]amine (1) to a large excess of nBuNa resulted in the formation of a mixed sodium amide/nBuNa complex. This is the first observation of such a complex. Addition of nBuLi to the chiral sodium amide dimer 3 gave a new mixed lithium/sodium amide 5. The use of 15N,6Li coupling constants showed that the lithium in 5 occupied the tetracoordinated site. The use of chiral sodium amide 3 in the desymmetrization of cyclohexene oxide gave a modest enantiomeric excess (ee) of 37%. The corresponding lithium amide gave an ee of 70% of the same enantiomer. This is the first example of the comparison of asymmetric induction by sodium as cation with that of lithium.

Journal Article↗
PubMed2001

Polaron dynamics in a system of coupled conjugated polymer chains.

The motion of excitations such as polarons is believed to be of fundamental importance for the transport properties of conjugated polymers for the use in, e.g., polymer based LED's. We have investigated polaron dynamics in a system of coupled polymer chains in the presence of an external electric field. In particular, we focus on how a polaron migrates through the polymer lattice, i.e., the situation in which a polaron reaches a chain end and is scattered to the surrounding chains. We show that the outcome of this event strongly depends on the strength of the electric field, and we identify three different cases for the polaron migration.

Journal Article↗
PubMed2001

Inhibition of hepatitis C virus NS3 protease activity by product-based peptides is dependent on helicase domain.

Structure activity relationships (SARs) of product-based inhibitors of hepatitis C virus NS3 protease were evaluated using an in vitro assay system comprising the native bifunctional full-length NS3 (protease-helicase/NTPase). The results were compared to previously reported data derived from the corresponding NS3 protease domain assay. Shortening the length of the protease inhibitors from hexapeptides to tripeptides revealed that the decrease in potency was much less when determined in the assay system with the full-length NS3 protein. Disagreements in SARs at different positions (P5 P2) were also discovered. Taken together, the results suggest that the impact of the helicase domain upon protease inhibitor binding is substantial.

DNA-Binding Proteins↗
PubMed2001

Parkinsonism and neck extensor myopathy: a new syndrome or coincidental findings?

BACKGROUND: Dropped head in parkinsonism has been attributed to dystonia or unbalanced muscle rigidity. To our knowledge, isolated neck extensor myopathy with parkinsonism has been described in only one patient. OBJECTIVES: To assess the occurrence of neck extension weakness resulting in dropped head in patients with parkinsonism and to explore whether the head drop might be the consequence of neck extensor myopathy. PATIENTS AND METHODS: All patients who were evaluated because of parkinsonism in the Department of Neurology in our hospital between January 1, 1997, and December 31, 1999, and were found to have both parkinsonism and neck extension weakness resulting in head drop were studied. The patients underwent clinical examination, blood tests including the levels of creatine kinase and myoglobin and neurophysiological evaluation with needle electromyography and autonomic tests. Open biopsy on a neck muscle was performed in the patients who could cooperate. RESULTS: Of 459 patients evaluated because of parkinsonism, 7 were found to have neck extensor weakness resulting in head drop. Needle electromyography revealed myopathic changes in all 7 patients. Muscle biopsy, which was performed in 5 patients, disclosed myopathic changes in all 5 patients. Electron microscopy revealed mitochondrial abnormalities in 2 of these 7 patients. Three of the patients had concomitant neck rigidity that could contribute to the neck position. All 7 patients had autonomic dysfunction and 6 responded poorly to levodopa therapy, making a diagnosis of multiple system atrophy probable. CONCLUSION: Parkinsonism may be associated with isolated neck extensor myopathy resulting in dropped head, and this condition should be suggestive of multiple system atrophy.

Aged↗
PubMed2001

Functional and morphological differences between human alveolar and interstitial macrophages.

Macrophages play an essential role in pulmonary host defense. They are, however, a heterogeneous cell population located in different lung compartments. This study was designed to elucidate differences between two macrophage populations obtained from the human lung, i.e., alveolar macrophages (AM) and interstitial macrophages (IM). Macroscopically tumor-free lung segments from nine patients undergoing lobectomy or pulmectomy were studied. All patients had a diagnosis of primary lung cancer. AM were recovered by bronchoalveolar lavage and IM were isolated by mechanical fragmentation of the lavaged lung segments followed by enzymatic treatment. The cell fractions were analyzed with respect to morphology (transmission electron microscopy) and function (phagocytosis). The cells in the IM fraction were smaller (7.6 +/- 1.8 microm (mean +/- SD) compared with 16.0 +/- 4.1 microm) and morphologically more heterogeneous than those in the AM fraction. Interestingly, a considerable portion of the cells in the IM fraction had a typical AM-like appearance. Despite this, the AM fraction had a higher phagocytic activity compared to IM, with faster attachment and ingestion processes (P <0.001 for both). We conclude that the heterogeneity of human lung macrophages must be taken into consideration when their role in the inflammatory response is studied.

Aged↗
PubMed2001

Passive versus active operator work in automated process control--a job design case study in a control centre.

Methods of avoiding common problems associated with operator work in automated process control, such as understimulation and difficulties in achieving and maintaining necessary skills and competence, are addressed in this paper. The source of these problems is deduced here to be that monitoring tasks are a predominant part of the job. This case study shows how work in a highly automated process can be designed not only to avoid the traditional problems, but also provide a stimulating job within a good work situation at the same time as fulfilling efficiency demands. A new definition of active/passive operator jobs is made which is based on a categorisation of the types of work tasks that make up the job. The definition gives an explanation of how different designs of operator jobs result in more or less active/passive work situations.

Adult↗
PubMed2001

Analysis of genetic changes in rat endometrial carcinomas by means of comparative genomic hybridization.

Animals of the BDII inbred rat strain are known to be genetically predisposed to endometrial adenocarcinoma (EAC). Using them as models of human EACs, we studied tumors arising in F1 and F2 progeny from BDII animals crossed to animals from two other inbred strains, in which EACs were quite rare. In order to identify chromosomal regions exhibiting DNA copy number changes, comparative genomic hybridization (CGH) was applied in a series corresponding to 27 different solid tumors, most of which were classified as EACs, from these animals. The main findings from the study were that, although many different chromosomes were involved in copy number variation, some of the changes detected were recurrent and quite specific. Among specific changes found were gains in rat chromosome (RNO) regions 4q12 approximately q22, 6q14 approximately q16, and whole chromosome arms in some of the small metacentric chromosomes (e.g., RNO14, 16, and 18). RNO10 was involved in gain in the terminal and proximal regions. Each of these regions contains previously identified cancer-related genes representing possible candidates to be involved in the development of EAC. Furthermore, it was observed that there were clear differences in the pattern of copy number changes between tumors occurring in the two different crosses, and also between solid tumors and cell cultures. Endometrial cancer is the most common human gynecological cancer, but not much is known about specific genetic changes influencing this disease. Two genetic alterations that have been reported from human endometrial cancer are amplification of the ERBB2 gene and mutations in the 12 codon of the KRAS gene. One case of Erbb2 amplification was found but there were no Kras mutations in the rat material studied. We conclude that molecular genetic analysis of the rat BDII model will provide important new information about EAC in mammals.

Adenocarcinoma↗
PubMed2001

Anomalous rates of evolution of pancreatic polypeptide and peptide tyrosine-tyrosine (PYY) in a tetraploid frog, Xenopus laevis (Anura:Pipidae).

The South African clawed frog Xenopus laevis is believed to have arisen as a result of a tetraploidization event occurring approximately 30 million years ago. Two molecular forms of pancreatic polypeptide (PP) have been isolated from an extract of the pancreas of this species and two molecular forms of peptide tyrosine-tyrosine (PYY) from the intestine. Despite the fact that the amino acid sequence of PP has, in general, been very poorly conserved during the evolution of tetrapods (only Pro(5), Pro(8), Gly(9), Ala(12), Tyr(27), Arg(33) and Arg(35) are invariant among species studied so far), the two Xenopus PPs differ by only a single amino acid substition (Asp(22)-->Glu). In contrast the two molecular forms of PYY differ by six amino acid substitutions (Glu(15)-->Gln, Thr(18)-->Ala, Leu(21)-->Met, Ile(22)-->Thr, Ile(28)-->Val, Val(31)-->Ile). The data imply that strong evolutionary pressure is acting to conserve the functional domain in both genes encoding PP and so suggest that PP may have an important physiological role in amphibians (although the nature of this role has yet to be determined). The more rapid mutation of the functional domain in the genes encoding PYY, a peptide whose amino acid sequence has been quite well conserved in tetrapods and whose physiological significance is well established, suggests that one of the PYY genes may be evolving towards a new function or towards becoming a pseudogene.

Amino Acid Sequence↗
PubMed2001

MRI staging using gadodiamide for soft-tissue tumors of the head and neck region. Results from a phase II trial and a 5-year clinical follow-up.

In order to document the safety, tolerability and efficacy of gadodiamide outside CNS, an open, non-drug comparative study was performed in patients with tumors of the head and neck region. Fifty adult patients were included and 48 patients received the contrast medium. The examinations were performed on a 1.5 T imager using transverse, non-enhanced T1- and PD-/T2-weighted conventional spin-echo sequences, followed by a contrast-enhanced transverse T1-weighted sequence. Post-contrast images provided more diagnostic information compared to unenhanced images in 33 of 48 patients (69%). This information was of significant help in four and of moderate help in 14 cases. Post-contrast images compared to non-enhanced T1-weighted showed improvement in lesion delineation for 29 of the 43 patients where a lesion was observed. Only in two patients was the diagnostic information lower post-contrast. A comparison between all pre-contrast images versus contrast medium enhanced showed post-contrast images to give more diagnostic information in 14 and less in nine patients. No patient experienced discomfort in relation to gadodiamide injection. Only one adverse event occurred which was described as thirst, being of moderate intensity. The 5-year clinical outcome was analyzed and compared with the pre-operative staging. The case-books of all patients were reviewed and in 44 patients all information could be found. Of those, 18 were still alive, one with active disease (AAD) and 17 with no evidence of disease (NED). Two of those four patients, where information was incomplete, showed NED and two had died. This trial showed that contrast-enhancement using gadodiamide for evaluation of soft tissue tumors in the head and neck region was safe and provided statistically significant more diagnostic information compared with unenhanced images. MRI, when compared with palpation/inspection, changed tumor staging in approximately 30% of all cases.

Contrast Media↗