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Biomedical subjects

H K Johansen

Publications and source records attributed to H K Johansen.

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

Effects of Chinese medicinal herbs on a rat model of chronic Pseudomonas aeruginosa lung infection.

The aim of the study was to evaluate the effects of two kinds of Chinese medicinal herbs, Isatis tinctoria L (ITL) and Daphne giraldii Nitsche (DGN), on a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF). Compared to the control group, both drugs were able to reduce the incidence of lung abscess (p < 0.05) and to decrease the severity of the macroscopic pathology in lungs (p < 0.05). In the great majority of the rats, the herbs altered the inflammatory response in the lungs from an acute type inflammation, dominated by polymorphonuclear leukocytes (PMN), to a chronic type inflammation, dominated by mononuclear leukocytes (MN). DGN also improved the clearance of P. aeruginosa from the lungs (p < 0.03) compared with the control group. There were no significant differences between the control group and the two herbal groups with regard to serum IgG and IgA anti-P. aeruginosa sonicate antibodies. However, the IgM concentration in the ITL group was significantly lower than in the control group (p < 0.03). These results suggest that the two medicinal herbs might be helpful to CF patients with chronic P. aeruginosa lung infection, DGN being the most favorable.

Agar↗
PubMed1995

Cross-reactive antigens shared by Pseudomonas aeruginosa, Helicobacter pylori, Campylobacter jejuni, and Haemophilus influenzae may cause false-positive titers of antibody to H. pylori.

Cystic fibrosis (CF) patients suffer from many of the gastrointestinal conditions which occur in non-CF individuals, e.g., dyspepsia and peptic ulceration. These symptoms may be caused by Helicobacter pylori but could also be due to either pancreatic insufficiency or the intensive antibiotic treatment used in CF patients. Since CF patients chronically infected with Pseudomonas aeruginosa produce antibodies against a wide range of antigens, including antigens common to many other bacteria, e.g., GroEL and lipopolysaccharide, we studied, by the Western blot (immunoblot) technique, the specificity of immunoglobulin G antibodies to H. pylori in Danish CF patients chronically infected with P. aeruginosa, CF patients without P. aeruginosa infection but with Haemophilus influenzae infection, patients with dyspeptic ulcers associated with H. pylori, and patients recovering from acute Campylobacter jejuni or Campylobacter coli infection. Sera from CF patients with chronic P. aeruginosa or H. influenzae infection and patients recovering from acute C. jejuni infection cross-reacted with H. pylori antigens. A strong cross-reacting protein antigen at approximately 14 kDa and minor cross-reactive antigens at approximately 27, 30, and 60 kDa (the heat shock protein GroEL is equivalent to the common antigen of P. aeruginosa) could be demonstrated. The results of this study show that high immunoglobulin G antibody titers against H. pylori in CF patients cannot be regarded as indicating present or past H. pylori infection unless their specificity is proven by absorption studies.

Antibodies, Bacterial↗
PubMed1995

Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia in rats.

In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF) we studied whether the inflammatory response could be altered by vaccination. Rats were immunized with either a depolymerized alginate toxin A conjugate (D-ALG toxin A), purified alginate, an O-polysaccharide toxin A conjugate, or sterile saline. After challenge none of the rats immunized with D-ALG toxin A died, in contrast to the other two vaccine groups combined (p = 0.03). A significant reduction in the severity of the macroscopic lung inflammation was seen in rats immunized with D-ALG toxin A, compared with the other three groups (p = 0.009). The histopathologic response in the control rats was dominated by numerous polymorphonuclear leukocytes (PMN) surrounding the alginate beads. In contrast, the histopathologic response in rats immunized with D-ALG toxin A changed within the first week after challenge from predominantly PMNs (TH2-like) to a chronic-type inflammation dominated by mononuclear leukocytes (TH1-like). In accordance, the antibody titers induced by the D-ALG toxin A vaccine were not different from those of the control rats after challenge. This study identifies a possible new way of modifying the inflammation and thereby preventing the PMN-mediated lung tissue damage during chronic P. aeruginosa lung infection in CF.

Alginates↗
PubMed1995

Experimental chronic Pseudomonas aeruginosa lung infection in rats. Non-specific stimulation with LPS reduces lethality as efficiently as specific immunization.

In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis, we investigated the possibility of preventing chronic lung inflammation or decreasing the progression of the infection. We compared the lethality, pathology, bacterial clearance, and immunogenicity after stimulation of the non-specific defence mechanisms by Escherichia coli lipopolysaccharide (LPS) or P. aeruginosa sonicate, or the acquired specific immune response by vaccination with the same bacterial antigens. One day prior to challenge with P. aeruginosa embedded in alginate beads, rats were stimulated with either E. coli LPS or P. aeruginosa sonicate. Four and two weeks prior to challenge other rats were vaccinated with either E. coli LPS or P. aeruginosa sonicate. Controls did not receive any stimulation or vaccination. The lethality after challenge was lower in rats stimulated with E. coli LPS (p = 0.02) or vaccinated with P. aeruginosa sonicate (p = 0.03) as compared to controls. The histopathology of the surviving rats showed an acute inflammation dominated by polymorphonuclear leukocytes (PMNs), but the offending bacteria were not completely eliminated in any group. The increased survival was probably due to earlier recruitment of PMNs most likely mediated by either cytokines and other chemotactic factors (stimulated group) or the immune response in concert with the complement cascade (vaccinated group). The results of the present and previous vaccination studies show that it is possible to improve survival but not to prevent the chronic P. aeruginosa lung infection and inflammation caused by alginate-embedded bacteria.

Animals↗
PubMed1994

[Biofilm, foreign bodies and chronic infections].

Most bacteria occur in the environment as sessile cells adhering to a surface, whereas a minority exists as free floating (planktonic) cells. Biofilms consist of microcolonies embedded in a polysaccharide matrix produced by the bacteria. This polysaccharide slime protects the bacteria against hostile environmental factors. Planktonic daughter cells are liberated from the surface of biofilms and may colonize new surfaces and subsequently produce new biofilms. Biofilms are often consortia of several different bacterial species. The normal microflora on the skin or on the mucous membranes in the human body occurs as a biofilm, which is removed by the shedding of old cells and by the excretion of mucus. Subsequently new cells and new mucus are colonized by biofilm forming bacteria without giving rise to any symptoms. When body surfaces with a normally occurring microflora (A) are connected by means of an implanted foreign body with body surfaces or tissue compartments without a microflora (B) e.g. bronchi, gall bladder, peritoneum, veins, then a translocation of the normal microflora from (A) to (B) may easily occur leading to acute infection, formation of new biofilms on the implanted foreign body and induction of inflammation in the environment of this biofilm. Chronic bacterial infections are frequently caused by biofilm producing bacteria and the pathogenesis of the tissue damage is dominated by a persistent immune complex mediated inflammation. Bacteria growing in biofilms cannot be eradicated by antibiotics and biofilms resist the immunological and non-specific defence mechanisms of the body.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1994

Immunization with Pseudomonas aeruginosa vaccines and adjuvant can modulate the type of inflammatory response subsequent to infection.

Pseudomonas aeruginosa is the predominant pathogen in patients with cystic fibrosis (CF). To study the possibility of preventing lung inflammation and decreasing the progression of the infection by vaccination, we have developed a rat model of chronic P. aeruginosa lung infection. Rats were immunized with P. aeruginosa whole-cell sonicates, O-polysaccharide toxin A conjugate, an alginate-toxin A conjugate, or native alginate. Control animals received sterile saline or incomplete Freund's adjuvant (IFA). The macroscopic (mean score, 2.4 versus 2.7 to 3.2) (P < 0.05) and microscopic (mean score, 2.0 versus 2.1 to 2.8) pathologic abnormalities were less severe in the control rats injected with sterile saline than in the immunized rats and the IFA group. The more severe lung abnormalities observed in immunized rats could be due to the result of immune complex-mediated lung tissue damage. The histopathologic results in the saline control rats were characterized by acute inflammation dominated by numerous polymorphonuclear leukocytes surrounding the alginate beads (microcolonies), as in CF patients. In contrast, the inflammatory response in the IFA group and in the immunized rats had changed from an acute-type inflammation to a chronic-type inflammation dominated by mononuclear leukocytes and scattered granulomas. Cross-reacting antibodies were induced by the two alginate vaccines, and most immunized animals developed a significant (P < 0.001) antibody titer elevation (in enzyme-linked immunosorbent assay) of the immunoglobulin M (IgM), IgG, and IgA classes against the homologous antigens. The bacterial clearance was significantly (P < 0.05) more efficient in most immunized rats than in the control rats given sterile saline. The present study shows that none of the vaccines could completely prevent chronic lung inflammation 4 weeks after challenge. However, the changed pathologic condition in immunized rats to a chronic-type inflammation might be of great benefit in future management of CF patients since the developing lung tissue damage has been shown to be caused by polymorphonuclear leukocyte-released elastase.

Animals↗
PubMed1994

Clearance of Pseudomonas aeruginosa from normal rat lungs after immunization with somatic antigens or toxin A.

In a recent study we observed that in most Danish CF patients a period of approximately one year of intermittent colonization precedes the onset of chronic P. aeruginosa lung infection. An experimental model of acute P. aeruginosa pneumonia in normal rats was utilized to investigate the possibility of improving bacterial clearance by vaccination. Rats were immunized with either P. aeruginosa whole bacterial sonicate, O-polysaccharide toxin A conjugate, alginate toxin A conjugate or purified alginate. Saliva and serum samples were obtained to investigate the potential of different vaccines to induce local IgA and systemic IgM, IgG and IgA antibodies. In all immunized rats a significant (p < 0.05) rise in antibody titers against the vaccine components could be demonstrated in both saliva and serum. The macroscopic pathological changes observed at 6, 24 and 48 h after bacterial challenge included a pronounced inflammatory reaction in all groups of rats, whether vaccinated or not (p > 0.05). Approximately 99.5% of the initial inoculum was cleared within the first 6 h after challenge in all groups of rats (p > 0.77). Four weeks after challenge no bacteria could be cultured and no sign of previous inflammation could be demonstrated in any of the groups. The results of this study show that the inflammatory reaction and the natural capacity to clear bacteria in the lungs of normal rats are very efficient against P. aeruginosa and could not be improved by immunization.

ADP Ribose Transferases↗
PubMed1993

Chronic Pseudomonas aeruginosa lung infection in normal and athymic rats.

We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic changes, and antibody responses. The rats challenged with P. aeruginosa alginate beads experienced a generally more severe lung pathology and the antibody responses were more homogeneous with less dispersion as compared to the rats having free live P. aeruginosa bacteria. In general, manifestations were more severe in the athymic rats compared to the normal rats. It is, however, notable that the athymic rats developed similar microscopic lung manifestations as the normal rats when given a large number of P. aeruginosa in the beads, with dense accumulation of neutrophil granulocytes and microcolonies comparable to the lesions seen in cystic fibrosis (CF) patients. Early transitory IgM titers were demonstrated in both normal and athymic rats. Whilst athymic rats produced much lower IgG titers than the normal rats, presumably due to the absence of CD4+ cells, higher primary IgA titers were achieved. These two models in normal and athymic rats of the chronic lung infection resembling that seen in CF lungs make it possible to study the influence of the various components of the specific and nonspecific defense systems on the course of the chronic P. aeruginosa lung infection and to evaluate the effect of various immunization schedules and immunomodulatory drugs.

Acute Disease↗
PubMed1992

Seasonal onset of initial colonisation and chronic infection with Pseudomonas aeruginosa in patients with cystic fibrosis in Denmark.

BACKGROUND AND METHODS: To assess the relation between seasonal variation and the onset of initial and chronic Pseudomonas aeruginosa infection, 300 Danish patients with cystic fibrosis were investigated. A retrospective analysis based on case reports was performed to identify the date and year of initial and chronic P aeruginosa infection from 1965 to 1990. RESULTS: Sixty six per cent of the patients contracted their initial P aeruginosa colonisation and 68% contracted chronic infection during the winter months (October to March). Despite major changes in treatment, including improved and intensified antibiotic treatment, during the investigation period in our cystic fibrosis centre, the seasonal difference in P aeruginosa infection persisted. CONCLUSIONS: As respiratory virus infections have the same seasonal distribution in Denmark such infections may pave the way for P aeruginosa and thus explain the parallel seasonal occurrence of this pathogen in patients with cystic fibrosis.

Chronic Disease↗
PubMed1992

Local IgA and IgG response to intratracheal immunization with Pseudomonas aeruginosa antigens.

We have experimentally immunized rats intratracheally with sonicated Pseudomonas aeruginosa to develop a high antibody response systemically and locally. The systemic antibodies were measured by a standard enzyme-linked immunosorbent assay (ELISA) on serum samples, whereas the local antibodies were measured on eluates from paper discs containing saliva. High levels of IgA antibodies were elicited in saliva whereas only traces of IgG antibodies were detected; the opposite results were found in serum. The saliva disc method permits serial measurements from the same animal and therefore offers the possibility to follow post-immunization antibody responses.

Animals↗
PubMed1991

[Manchincel poisoning complicated by streptococcal pharyngitis and impetigo].

A Danish tourist to Antigua in the West Indies, ate a fruit of Hippomane mancinella and developed acute poisoning with blistering of the oral mucosa and diarrhoea and a streptococcal superinfection. Ignorant tourists and their travel advisers are warned against this potentially deadly apple-tree-like plant and its tempting fruits.

Adult↗
PubMed1991

Severity of cystic fibrosis in patients homozygous and heterozygous for delta F508 mutation.

To assess the relation between genotype and severity of disease in cystic fibrosis (CF) the frequencies and extent of several features of its phenotypic expression were investigated in the 235 patients who attend the Danish CF Centre. 14 patients who attend irregularly and 3 who do not carry the delta F508 mutation at all were excluded. The case-reports of the remaining 218 patients (aged 4 months to 41 years) were carefully evaluated, and they were all analysed for the delta F508 mutation. 172 (79%) were homozygous for delta F508 and 46 (20%) were heterozygous. The mutation therefore occurs on 89% of the chromosomes analysed. There were no significant differences between the homozygous and heterozygous groups in the proportions with meconium ileus at birth, liver involvement, or chronic Pseudomonas aeruginosa infection. However, significantly more of the homozygous patients had onset of symptoms before the age of 6 months (p less than 0.025); they were significantly younger at diagnosis (p = 0.013) and centre referral (p = 0.006); they required greater pancreatic enzyme substitution (p = 0.0002) and had poorer lung function; and the calculated yearly incidence of chronic Ps aeruginosa infection and yearly mortality rates were greater than in heterozygous patients (p = 0.0001).

Adolescent↗
PubMed1991

[Generalized toxic symptoms caused by Clostridium difficile infection in a patient with Wilms' tumor].

This case report describes a 15 months-old patient with Wilms' tumor, who was treated with radical operation and chemotherapy. During hospitalization the patient suffered from recurrent lung infections, which were treated with appropriate antibiotics. Subsequently, the patient developed severe abdominal affection with daily melena, liver and kidney involvement, and generalized edema and hypertension. Cl. difficile and its cytotoxin was demonstrated in feces, and the patient was successfully treated with vancomycin. Although rare, Cl. difficile may cause severe generalised illness in children under two years of age, and it is important to examine any infant with abdominal symptoms for the occurrence of Cl. difficile, even though no diarrhoea is present.

Clostridioides difficile↗
PubMed1991

Experimental immunization with Pseudomonas aeruginosa alginate induces IgA and IgG antibody responses.

We tried experimentally to induce a specific antibody response against Pseudomonas aeruginosa locally in the airways and systemically in rats by three different routes of immunization; intragastric feeding, intratracheal inoculation or subcutaneous vaccination. Three groups of rats were immunized with live mucoid P. aeruginosa PAO 579 by intragastric feeding or with killed PAO 579 intratracheally or subcutaneously. Three other groups were immunized with purified P. aeruginosa alginate either by intragastric feeding, intratracheally or subcutaneously. At weekly intervals for four weeks animals were sacrificed and serum and bronchial fluid were obtained. The specific IgA and IgG antibody response in lavage fluid and serum was measured. Only traces of antibodies could be detected in the bronchial lavage fluids. Anti-alginate IgA and IgG antibodies developed in all rats immunized with alginate but no antibodies against other P. aeruginosa antigens were detected. The highest IgA and IgG titer against alginate was induced by the subcutaneous immunization. IgA and IgG antibodies against other P. aeruginosa antigens developed in rats immunized with liver and sonicated bacteria. The highest IgA and IgG titers were obtained after intratracheal and subcutaneous immunization with sonicated bacteria. The present work has shown that IgA and IgG antibodies develop with high specificity after immunization. The different titers obtained do not necessarily reflect different degrees of protection.

Alginates↗
PubMed1990

Changes in T1 relaxation processes in the bone marrow following treatment in children with acute lymphoblastic leukemia. A magnetic resonance imaging study.

Magnetic resonance imaging (MRI) and T1 relaxation time measurements of the vertebral bone marrow were performed in 11 children with acute lymphoblastic leukemia (ALL) at diagnosis. Nine of the children were re-examined after chemotherapeutic treatment. The results were compared with histological data from bone marrow biopsies obtained in close association to the MR examinations. Ten age matched children were examined as a control group. A 1.5 Tesla whole body scanner was used for the measurements. The pretreatment T1 relaxation times of the bone marrow were significantly prolonged, compared to the age matched controls. After chemotherapy the T1 relaxation times of the children with ALL decreased significantly towards or into the normal range. A significant correlation was found between the T1 relaxation time and the content of malignant blast cells in the bone marrow.

Adolescent↗
PubMed1990

Frequency of the delta F508 mutation on cystic fibrosis chromosomes in Denmark.

We have investigated the frequency of the delta F508 mutation on cystic fibrosis (CF) chromosomes in Denmark. Of 304 chromosome tested, 86.8% have the delta F508 mutation. The majority of the chromosomes with this mutation are found on chromosomes with the XV2c/KM19 haplotype B (97.3%), whereas 15/16 chromosomes with haplotype C have another mutation, confirming that only very few mutations will account for the majority of CF genes in the Danish population.

Cystic Fibrosis↗