Biomedical subjects

B Johansen

Publications and source records attributed to B Johansen.

At least 55 records · Page 3Linked to original sources

PubMed1996

Extracellular phospholipase A2 expression in sarcoidosis.

This study was conducted in order to focus upon the Ca2- dependent secretory non-pancreatic phospholipase A2 (npPLA2) enzyme and its possible role in the pathophysiology of sarcoidosis. Serum samples were taken from 24 patients with sarcoidosis to determine the levels of npPLA2. Moreover, in another group of patients with active chest x-ray stage II and III sarcoidosis, bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial lung biopsies (TBL) were taken. Highly significant increase of npPLA2 in serum was found in patients compared to controls (p < 0.001). Furthermore, those patients with stable and inactive disease and those who were under treatment with corticosteroids, tended to have lower values than those with active disease and those who were untreated. An intense accumulation of npPLA2 was found in smooth muscle tissue in lung biopsy specimens, in close connection with fibroblast accumulation and deposition of collagen. These cells also stained positive for alpha-smooth muscle actin (alpha-SMA). In addition, when using the technique of in situ hybridization, expression of npPLA2-mRNA was found in the fibroblast layer surrounding the epitheloid cell granulomas. These fibroblasts did not stain positive for alpha-SMA. Our data suggest that npPLA2 is actively involved, and has an important role, in the pathophysiology of sarcoidosis.

Actins↗

PubMed1995

In vivo expression of a single viral DNA-binding protein generates systemic lupus erythematosus-related autoimmunity to double-stranded DNA and histones.

Although the origin of autoimmune antibodies to double-stranded DNA is not known, the variable-region structures of such antibodies indicate that they are produced in response to antigen-selective stimulation. In accordance with this, results from experiments using artificial complexes of DNA and DNA-binding polypeptides for immunizations have indicated that DNA may induce these antibodies. Hence, the immunogenicity of DNA in vivo may depend upon other structures or processes that may render DNA immunogenic. We report that in vivo expression of a single DNA-binding protein, the polyoma virus T antigen, is sufficient to initiate production of anti-double-stranded DNA and anti-histone antibodies but not a panel of other autoantigens. Expression of a mutant, non-DNA-binding T antigen did result in strong production of antibodies to the T antigen, but only borderline levels of antibodies to DNA and no detectable antibodies to histones. Nonexpressing plasmid DNA containing the complete cDNA sequence for T antigen did not evoke such immune responses, indicating that DNA by itself is not immunogenic in vivo. The results represent a conceptual advance in understanding a potential molecular basis for initiation of autoimmunity in systemic lupus erythematosus.

3T3 Cells↗

PubMed1995

[Guidelines for understanding and treating chronic obstructive lung diseases. Institute for Pharmacotherapy].

A group of chest physicians, general practitioners, clinical pharmacologist and pharmacists appointed by the Institute of Pharmacotherapy, University of Oslo has evaluated the present knowledge about treatment of chronic obstructive lung disease. The group discusses today's medical treatment of this rather numerous group of patients. It is stated that, to a high degree, the treatment of these patients lacks proper documentation, and that treatment needs to be tested out on an individual basis. The group proposes a flow chart for this purpose.

Humans↗

PubMed1994

A two fusion partner system for raising antibodies against small immunogens expressed in bacteria.

Production of antisera against proteins that are not amenable to easy purification is most efficiently achieved by expressing the protein as a fusion product in bacteria. However, smaller polypeptides may present difficulties, since the majority of the antibodies may be directed against the fusion partner if the whole fusion protein is used as immunogen, while the target peptide alone may be a poor immunogen due to its small size. We have circumvented this problem through the use of two different fusion partners. The first fusion protein is used for priming the immune response and the first boost, while another fusion partner is substituted for the second boost. Five different polypeptides derived from the human polyomavirus BK, ranging in molecular weight from 4400 (39 amino acid residues) to 11,500 (96 amino acid residues), were used to test this approach. The results obtained indicate that this procedure may be very useful in raising antibodies against small antigens.

Animals↗

PubMed1994

Elevated expression of human nonpancreatic phospholipase A2 in psoriatic tissue.

In involved psoriatic tissue, which is characterized by chronic inflammation in both epidermis and dermis, elevated levels of arachidonic acid and eicosanoids have been measured. This implies that a phospholipase A2 (PLA2) may be involved in the pathogenesis of psoriasis. The PLA2's are a group of enzymes that release unsaturated fatty acids from the sn2-position of membrane phospholipids. Once released, the fatty acids are converted by various enzymes into biologically very important signaling molecules. Release of arachidonate initiates the arachidonate cascade, leading to the synthesis of eicosanoids such as prostaglandins, thromboxanes, leukotrienes, and lipoxines. Eicosanoids are important in a variety of physiological processes and play a central role in inflammatory mediators, such as lyso-PAF (a precursor for PAF) and other lysophospholipids, may also be formed through the action of a PLA2. We report for the first time the detection of transcripts of nonpancreatic phospholipase A2 (npPLA2, type II) and cytosolic (c) PLA2 in human skin, and overexpression of npPLA2 in involved skin from patients with psoriasis (plaque psoriasis and pustular psoriasis). Limited amounts of npPLA2 enzyme are detected immunologically in the uppermost layers of epidermis from healthy persons. Both involved and uninvolved psoriatic epidermis contain higher levels of npPLA2 than normal skin. Positive cells in dermis showed significantly higher levels of npPLA2 than epidermal cells. In dermis from healthy persons, only weak staining of a few cells could be detected. The two PLA2 enzymes detected in psoriatic skin (cytosolic and nonpancreatic) may both be involved in eicosanoid overproduction in psoriatic tissue, and the npPLA2 may also be involved in potentiating cell activation, especially T cells.

Fibroblasts↗

PubMed1994

Immunohistologic detection of non-pancreatic phospholipase A2 (type II) in human placenta and its possible involvement in normal parturition at term.

Placenta is one of the richest sources of non-pancreatic phospholipase A2 (npPLA2) (type II) in the human body, and the enzyme is the key enzyme releasing unsaturated fatty acids from membrane phospholipids. Prostaglandins (PGs) play a critical role in the initiation and progression of parturition. Cytokines are presumed to play a central role in the initiation of normal labor at term, and cytokines are also found to regulate both synthesis and secretion of npPLA2 enzyme. In an attempt to resolve the physiologic function of the npPLA2 enzyme in placental tissue, immunohistologic localization and enzymatic activity measurements of npPLA2 enzyme were performed. NpPLA2 protein was detected in vascular smooth muscle, endothelial cells and connective tissue cells in placenta and umbilical cord, and the protein was weakly stained in trophoblast cells in placenta. Enzymatic activity was not increased in sera from mother nor child compared to sera from healthy individuals, but the activity in amniotic fluid was considerably higher. Our findings support the candidacy for npPLA2 in enzymatic arachidonic acid release from foetal membranes.

Amniotic Fluid↗

PubMed1994

Deaths from pulmonary tuberculosis in a low-incidence country.

OBJECTIVES: To study the validity of official mortality statistics regarding deaths from pulmonary tuberculosis, and to identify factors contributing to death. DESIGN: A retrospective study. SETTING: Cases were enrolled from the data of the Central Bureau of Statistics from where the official mortality statistics are issued, the National Tuberculosis Register and all Autopsy Registers in the region. SUBJECTS: Case and autopsy reports from all patients who died from active pulmonary tuberculosis in two Norwegian counties between 1977 and 1989. MAIN OUTCOME MEASURES: Patients identified from all three registers with active pulmonary tuberculosis, concomitant diseases/risk-factors, chest X-rays, symptoms, number of patients investigated and treated for tuberculosis, duration from hospital admission until start of treatment and/or death. RESULTS: Ninety-six patients, median age 75 years, died from pulmonary tuberculosis, 51 without treatment. Thirty-four patients had not been registered at the Central Bureau of Statistics. Thirty-nine patients had cough on admission. Weight loss and generalized malaise occurred just as frequently. Forty-two patients had infiltrates on chest X-ray located elsewhere than in the apical region. In 42 patients, no diagnostic tests for tuberculosis were performed. The median length of stay in hospital was 24 days before death in the untreated group, and 21 days before start of treatment in the treated group. CONCLUSION: Reliable figures of patients who died from pulmonary tuberculosis could not be obtained from the official statistics because of under-notification and erroneous codification of diseases. Deaths occurred mainly because the diagnosis was established too late: in half of the patients at autopsy. Eighty-one patients had concomitant diseases known to lower resistance against tuberculosis. Lack of diagnostic suspicion may have been caused by nonspecific symptoms and atypical chest X-ray findings.

Adult↗

PubMed1994

A steroid hormone response unit in the late leader of the noncoding control region of the human polyomavirus BK confers enhanced host cell permissivity.

The effect of steroid hormones on multiplication of the human polyomavirus BK (BKV) was studied. Physiological concentrations of the synthetic glucocorticoid dexamethasone, progesterone R5020, or estrogen 17 beta-estradiol enhanced the permissivity of the host cell for BKV, resulting in an up to 11-fold (dexamethasone), 5-fold (progesterone), or 3-fold (17 beta-estradiol) higher virus yield. The increase in virus yield in dexamethasone-stimulated cells correlated with enhanced steady-state levels of viral transcripts. The late leader sequence of the BKV control region contains a hormone response unit composed of a nonconsensus glucocorticoid and/or progesterone response element (GRE/PRE) and a fully consensus estrogen response element (ERE). DNA-protein binding studies showed that the glucocorticoid receptor and the progesterone receptor bound to this BKV GRE/PRE-like sequence, while the estrogen receptor could bind to the BKV ERE motif. By transient transfection assays, we were able to show that these sequences can mediate steroid hormone-induced gene expression. However, no cooperative transactivation effect between the BKV GRE/PRE-like motif and BKV ERE motif was observed. This BKV hormone response unit may play an important role in vivo by enhancing a productive BKV infection, and perhaps also by reactivating a latent infection, during physiological or pathological conditions accompanied by increased steroid hormone levels.

Animals↗

PubMed1994

Single lung alveolar volume and gas transfer: effect of expansion of the other lung.

BACKGROUND: Temporary occlusion of one mainstem bronchus permits measurement of single lung function. A previous study suggested that the volume at which one lung is occluded may influence the expansion of the other. The effect of ipsilateral occlusion volume on the contralateral effective alveolar volume (VA, EFF,SL), inspired volume (VI,SL), single breath estimated residual volume (RVSB,SL), carbon monoxide (CO) transfer (TLCO,SL) and transfer coefficient (KCO,SL) has been examined. METHODS: Single breath measurements of CO transfer were made in duplicate in 12 healthy subjects aged 19-44 years, without and during occlusion of one mainstem bronchus by a balloon at RV and at total lung capacity (TLC). RESULTS: Mean VA,EFF,SL, VI,SL, and TLCO,SL were lower during occlusion at RV than during occlusion at TLC (2.84 v 3.26 l; 2.18 v 2.54 l; and 4.70 v 5.51 mmol/kPa/min respectively). RVSB,SL was independent of occlusion volume and KCO,SL not different from the KCO of both lungs (KCO,BL). Single lung values during occlusion at TLC were fairly reproducible and were, except for KCO,SL, approximately half the values for both lungs. During occlusion at RV the second TLCO,SL and KCO,SL were lower than the first. CONCLUSIONS: Occlusion of one lung permits reliable determinations of gas transfer indices of the other, provided the lung is occluded at TLC. Occlusion at RV significantly reduces VA,EFF,SL, and hence TLCO,SL, but does not affect KCO,SL of the other lung.

Adult↗

PubMed1993

The c-fos cAMP-response element: regulation of gene expression by a beta 2-adrenergic agonist, serum and DNA methylation.

The transcription control region of the proto-oncogene c-fos contains multiple cis-acting elements to which specific trans-acting factors bind. One such well-studied binding motif in the c-fos promoter is the major cyclic AMP response element (CRE) TGACGT located at -62/-57. In this study we investigated the role of this element in gene regulation by beta 2-adrenergic/adenylate cyclase signalling and DNA methylation. By transient gene expression assays we were able to show that the c-fos regulatory sequences spanning nucleotides -361 to +13 could mediate gene expression by the beta 2-adrenergic agonist isoproterenol and the phosphodiesterase inhibitor theophylline. For isoproterenol however, a stimulating effect was observed in serum-starved cells, while an inhibitory effect was measured in cells supplemented with serum. The gene regulation by the cAMP elevating agents could be due, at least partially, to the major CRE since this isolated motif mediated gene expression by these drugs. Distinct protein-DNA complexes were obtained with nuclear extracts prepared from cells exposed to isoproterenol or/and theophylline under different serum conditions. We further show that DNA methylation of this CRE may also be involved in gene regulation as methylation of the CRE motif strongly reduced the binding of nuclear proteins.

Adrenergic beta-Agonists↗

PubMed1993

Long-term follow-up of pulmonary function in patients cured from testicular cancer with combination chemotherapy including bleomycin.

A follow-up study of pulmonary function in two groups of patients with testicular cancer was performed 6-12 years after treatment. Both groups, 47 patients in each, had undergone retroperitoneal lymph node dissection (RPLND). Patients with pathological stage (ps) II had also received bleomycin (median 270 mg) and cisplatin (median 540 mg) in three or four courses which included vinblastine or etoposide. Patients in ps I and II were similar with respect to age, general health, observation period, inspired oxygen fraction (FiO2) and maximal arterial oxygen pressure (pO2) at RPLND, but four (8.2%) with psII disease developed densities on chest X-ray during chemotherapy. At the long-term follow-up the groups were similar with respect to physical exercise, smoking pattern, present drug treatment and history of cardiopulmonary disease. In both groups forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and single breath transfer factor for carbon monoxide (TLCO) were within normal limits, and no difference was found between the groups. The combined data for both groups showed that smoking was highly associated with impairment in TLCO (P = 0.005), and smoking frequency was negatively correlated to TLCO (P = 0.002). We conclude that 3-4 courses with bleomycin, cisplatin and etoposide/vinblastine in testicular cancer patients do not lead to long-term impairment of pulmonary function.

Adolescent↗

PubMed1993

Serum immunoglobulin G subclasses and serum immunoglobulin A in acute bronchiolitis in infants.

Serum IgG subclasses and Serum IgA were studied in 43 infants with acute bronchiolitis and 20 healthy infants. IgG subclasses were determined by a capture ELISA and IgA was quantified by turbidimetry. IgG1 concentrations were significantly lower in infants with bronchiolitis than in normal infants. The other IgG subclasses and IgA did not differ between the groups. The subgroups of infants with bronchiolitis who had previously suffered from otitis media or bronchitis, had significantly lower IgG2 than the other infants with bronchiolitis. The same was found for infants with bronchiolitis who had suffered from three or more lower respiratory tract infections. In infants who had suffered from upper or lower respiratory infections before the acute bronchiolitis, IgA was significantly higher than in infants without previous respiratory infections. Ten infants with bronchiolitis (23%) had IgG1 deficiency, that is values below the lower reference limit calculated in a population of healthy Norwegian infants. No healthy infants had any IgG1 deficiency. No infant with bronchiolitis had IgG2 or IgG3 deficiency. The low IgG1 values found in infants with acute bronchiolitis, may be one cause for infants to be more susceptible to RS virus infections.

Acute Disease↗

PubMed1993

Static lung volumes in healthy subjects assessed by helium dilution during occlusion of one mainstem bronchus.

BACKGROUND: Single lung function is usually assessed by radioisotopes or, more rarely, by bronchospirometry in which a double lumen catheter is used to separate ventilation of the two lungs. The latter is more precise but less comfortable. An alternative bronchoscopic method is described for determining the volume of a single lung. METHODS: One mainstem bronchus was temporarily occluded with an inflatable balloon during fibreoptic bronchoscopy in 12 healthy volunteers aged 18-29 years. The functional residual capacities (FRC) of the right, left, and both lungs were measured in duplicate by closed circuit helium dilution. Supplementary vital capacity (VC) manoeuvres permitted calculation of single lung capacities (TLC) and residual volumes (RV). RESULTS: The standard deviation of a single determination of capacities of the right, left, and both lungs were: TLC, 80, 96, and 308 ml; VC, 56, 139, 171 ml; FRC, 131, 74, and 287 ml; RV, 112, 185, and 303 ml, respectively. The sum of the right and left unilateral TLC was not different from bilateral TLC (6.12 v 5.95 l) and the sum of the unilateral FRC was not different from the bilateral FRC (2.60 v 2.78 l). The sum of the unilateral VC was lower than bilateral VC (4.52 v 4.80 l), that of the unilateral RV was higher than bilateral RV (1.60 v 1.16 l). For all subdivisions of lung volume, the right lung was larger than the left. The most common complaint was substernal discomfort during complete exhalation. Oxygen saturation rarely fell below 90%. CONCLUSIONS: Temporary occlusion of a mainstem bronchus in normal subjects is safe, relatively simple, and allows fairly precise and accurate measurements of unilateral static lung volumes. Occlusion at TLC, however, probably prevents proper emptying of the non-occluded lung.

Adolescent↗

PubMed1993

Daily home spirometry facilitates early detection of rejection in single lung transplant recipients with emphysema.

Eight single lung transplant recipients with emphysema, aged 40-58 yrs, have been followed up for 90 patient months. Starting 2-4 weeks postoperatively, they recorded their forced vital capacity (FVC), and forced expiratory volume in one second (FEV1), at a fixed time every morning using a Micro Spirometer. They were instructed to contact the hospital if the FVC or FEV1 displayed a persistent (two days or more) decrease of 10%, compared with the average values during the last seven days. Transbronchial biopsies (TBB) were performed regularly in the follow-up, and whenever the patients had respiratory symptoms, or the FVC or FEV1 displayed a persistent decline of more than 10%. We performed 59 TBBs, and 23 biopsy specimens showed rejection. The FVC and FEV1 values on the TBB day were compared with the mean values of the 7 previous days. FVC and FEV1, associated with negative TBBs (16 events), showed no significant changes. However, FVC and FEV1 decreased significantly (p < 0.001, paired t-test) during rejections (mean percentage change 14 and 21% respectively, range +8% to -53%). In 16 of the 23 rejections, the FEV1 decreased by > 10%. We recommend the use of daily home spirometry when monitoring single lung recipients with emphysema, and suggest that a persistent 10% decrease in FEV1 or FVC for at least two days is an indication for hospital admission and possible TBB.

Adult↗

PubMed1992

Expression, purification and biochemical comparison of natural and recombinant human non-pancreatic phospholipase A2.

The gene coding for human non-pancreatic phospholipase A2 (npPLA2) was cloned in a eukaryotic expression vector and transfected into chinese hamster ovary (CHO) cells. A number of cell lines stably expressing npPLA2 were obtained. Northern analysis of these cell lines showed an abundant transcript of expected size 1200 nt. The recombinant enzyme was efficiently secreted in quantities up to 400 micrograms npPLA2 per liter culture medium in the most productive cell lines. npPLA2 was purified to homogeneity from conditioned medium as previously described (1). The recombinant npPLA2 migrated by SDS--PAGE as a single band with an apparent mass of 14,000. The recombinant enzyme displayed the pH-optimum, calcium dependence and substrate preference that were characteristic of the human platelet and synovial fluid enzymes.

Animals↗

PubMed1992

[Mortality in operable lung cancer].

We have retrospectively examined the medical records and prospectively studied the survival of the 50 men and 26 women who underwent surgery for primary non-small cell lung cancer at our hospital during the period 1982 to 1986. Adenocarcinoma was the predominant histologic type of tumour (55%). Pneumonectomy was performed in only 17% of the cases. Surgery was considered to be radical in 54 patients. This was not dependent on sex, histology or type of resection. 60% of the patients were alive after three years. Almost all of them had undergone radical resection. The surviving patients (at follow-up 1 July, 1990) had been younger at the time of surgery and had a lower erythrocyte sedimentation rate than those who had died. As a group, however, they had not lived longer than those who died.

Adult↗

PubMed1992

Development of a gene transfer system for curing of plasmids in the marine fish pathogen Vibrio salmonicida.

All reported natural isolates of the marine fish pathogen Vibrio salmonicida contain plasmids, and in another marine fish pathogen, Vibrio anguillarum, it has been shown that a plasmid is important for expression of virulence by the organism. To study the function of the plasmids in V. salmonicida, we developed a gene transfer system based on the plasmid RSF1010 replicon. The gene transfer system was used to construct a plasmid-free strain, and this strain was found to behave similarly to the wild type in a fish pathogenicity test based on intraperitoneal injection of the bacteria. We were unable to detect any other phenotypic differences between the two strains. It could therefore be concluded that at least in the V. salmonicida strain tested, extrachromosomal DNA is not required for expression of virulence.

Animals↗

PubMed1992

Single lung transplantation. Surgical experiences with the first seven patients.

Seven single lung transplants are reported. The patients were severely disabled and oxygen dependent below sixty years of age with a poor prognosis. Diagnosis were alfa 1-antitrypsin deficiency (3), sarcoidosis (3) and idiopathic emphysema (1). Multiorgan-harvesting including six hearts, was performed in local or distant hospitals (3). Partial cardiopulmonary bypass simplified transplantation. The surgical procedure was modified with a direct transpericardial approach. Soft tissue wrapping by a vascularized pedicle secured the bronchial anastomosis. The four drug immunosuppressive regimen included cyclosporin A, azathioprine, steroids and antithymocyte globulin. Primary graft function was excellent. Six patients survived the postoperative period and are alive 5-19 months post transplant. Transbronchial biopsies and lung function studies have been helpful in detecting pulmonary rejections. Patient rehabilitation is satisfactory in most patients with improvement in physiologic parameters.

Adult↗