Down-regulation of survivin alleviates experimental arthritis.

Survivin is a proto-oncogene that regulates cell division and apoptosis. It is a molecular marker of cancer. Recently, survivin has emerged as a feature of RA, associated with severe joint damage and poor treatment response. The present study examined if inhibition of survivin affects experimental arthritis, which was induced in mBSA-immunized mice by an injection of mBSA in the knee joint or developed spontaneously in collagen type II-immunized mice. The inhibition of survivin transcription by a lentivirus shRNA construct alleviated joint inflammation and reduced bone damage. The inhibition of survivin reduced the levels of metalloproteinases, ß-catenin, and vimentin, limiting the invasive capacity of synovia, while no inhibition of osteoclastogenesis could be found. The inhibition of survivin led to a p53-independent reduction of T cell proliferation and favored the transcription and activity of Blimp-1, which limited IL-2 production and facilitated formation of regulatory Foxp3(+)CD4(+) and effector CD8(+) T cells. The study shows that the inhibition of survivin is sufficient to reduce joint inflammation and bone damage in preclinical models of arthritis. Antiarthritic effects of survivin inhibition are related to p53-independent control of lymphocyte proliferation.

A method for measuring the potential dermal exposure to methyl methacrylate during two different dental technical work tasks.

Dental technicians are exposed on a daily basis to undiluted methyl methacrylate (MMA) when performing various routine tasks. Although the clinical effects of this chemical have been known for decades, no previous studies have been performed to estimate the potential dermal exposure to it. In this study we describe a patch-sampling technique to intercept the MMA that would otherwise have contaminated the skin on different parts of the hand and lower arm. Two different work tasks, making an orthodontic splint and denture preparation, were both performed under simulated workplace conditions twice by two recent graduated dental technicians. Air measurements were collected simultaneously. The results indicate that the exposure patterns associated with producing an orthodontic splint and denture preparation differed. We found work task-dependent differences in the amounts of MMA collected at the different parts of each hand, and differences between the right and left hands. There was also an interaction between hand and work task, especially for the right hand. The air measurements were positively correlated with the dermal exposure. This study highlights the importance of using a measurement strategy that takes the variability within the hand/arm body parts into account when measuring potential exposure during these kinds of work tasks. In order to establish future dermal exposure limits, more workplace and experimental studies are required.

Extracellular cytochrome c, a mitochondrial apoptosis-related protein, induces arthritis.

OBJECTIVES: The aim of the study was to assess the role of extracellular cytochrome c as an inducer of joint inflammation and to examine its levels in sera and synovial fluids of rheumatoid arthritis (RA) patients. METHODS: Mice were injected intra-articularly with different doses of cytochrome c and joints were evaluated histopathologically and immunohistochemically 3 and 10 days later. In addition, mouse spleen cells were stimulated with different concentrations of cytochrome c, followed by assessment of NF-kappaB activation and cytokine production. Sera and synovial fluid from RA patients and sera from healthy individuals were assessed with respect to cytochrome c levels by an enzyme-linked immunoassay technique. RESULTS: Histopathological signs of arthritis were evident in 75% of animals following intra-articular injection of cytochrome c. Synovitis was characterized by influx of Mac-1+ cells. In vivo depletion of neutrophils and monocytes led to abrogation of arthritis. Stimulation of mouse spleen cells in vitro with cytochrome c resulted in activation of NF-kappaB and release of proinflammatory cytokines and chemokines. Cytochrome c levels in RA patients' sera were significantly lower than in healthy controls. Further, cytochrome c levels in synovial fluid were significantly lower than in corresponding blood samples. CONCLUSIONS: Our findings demonstrate that extracellular cytochrome c displays direct proinflammatory properties mediated by activation of NF-kappaB and causing neutrophil and monocyte triggered inflammation. We hypothesize that decreased levels of cytochrome c in RA patients reflect consumption of this molecule in the synovial tissue, decreasing apoptosis and shifting the balance towards inflammation.

Genistein as an anti-inflammatory agent.

OBJECTIVE AND DESIGN: The aim of this study was to investigate the impact of the isoflavone genistein on in vivo cell-mediated responses. In addition, we wanted to study the influence of genistein on collagen induced arthritis (CIA) in mice. METHODS: Delayed type hypersensitivity reaction (DTH) to oxazolone and the inflammatory response to olive oil were measured in mice treated with genistein. In addition, the impact of genistein treatment on disease progression and outcome of collagen induced arthritis (CIA) was examined. RESULTS: The DTH reaction to oxazolone and the granulocyte-mediated response were significantly suppressed in genistein-treated as compared to control mice. Also, genistein treatment led to decreased levels of oxazolone-specific antibodies. Histologically, mice exposed to genistein and immunized with collagen II displayed somewhat lower degree of inflammation and joint destruction. In addition, serum levels of autoantibodies to collagen II were significantly lower following genistein-treatment in immunized mice. CONCLUSION: We conclude that genistein exerts evident anti-inflammatory properties affecting granulocytes, monocytes, and lymphocytes.

Mutuality as background music in women's lived experience of mental health and depression.

Mental health problems, especially depression, have turned into an extensive public health problem, affecting women in particular. The aim of this study was to obtain a deeper understanding of mental health phenomena through elderly women's lived experiences of mental health and depression. The phenomenological approach was chosen for collecting experience-based and person-centred descriptions from 21 women, focusing on mental health and depression. The interviews were analysed using Giorgi's phenomenological descriptive method. Mutuality in their relationships with themselves and others emerged as a major element in the women's experience of mental health and depression. When the women's existence and value were confirmed in relation to themselves and others, mental health appeared as an ascending spiral. When the women's value and self-esteem in relation to themselves and others were violated, the result was a descending spiral. Metaphorically speaking, 'mutuality' provided the 'background music' to the women's lives. Being a skilled professional psychiatric nurse means making the best use of mutuality as a creative power in the nurse-patient relationship. This means that the nurse must be aware that her/his attitude, appearance and behaviour are interpreted as a confirmation of the patient's worthiness or worthlessness.

Total abrogation of collagen II-induced arthritis and the B cell response to type II collagen using suboptimal doses of a topoisomerase II antagonist.

BACKGROUND: Collagen-induced arthritis (CIA) is the most commonly used model of rheumatoid arthritis (RA). In both CIA and RA there is an increase in the cellular content of the synovium, this being dominated by macrophages. OBJECTIVE: To assess the impact of etoposide, a topoisomerase II antagonist known to induce monocyte apoptosis, on the development of CIA. METHODS: Mice were primed and booster immunised against collagen II (CII). One group of mice was treated with etoposide two days before CII immunisation and then on four consecutive days weekly until the end of the experiment. The second group of mice was injected with etoposide on four consecutive days a week starting 40 days after CII priming. The third group of mice were controls receiving phosphate buffered saline (PBS). The mice were examined for development of arthritis, numbers of circulating leucocytes, serum CII antibody, and cytokine concentrations. RESULTS: None of the mice given etoposide before CII immunisation developed arthritis. Serum concentrations of anti-CII antibodies were undetectable in these mice, whereas they displayed significantly increased concentrations of interferon gamma and interleukin 6. In addition, the CII specific B cell responses in the draining lymph nodes were highly suppressed. Also, mice treated with etoposide at the onset of clinical arthritis showed reduced frequency of their disease by 50%. CONCLUSION: There was a striking disease alleviating impact of topoisomerase II antagonist on the course of CII-induced arthritis.

Model systems: modeling human staphylococcal arthritis and sepsis in the mouse.

The staphylococci have been recognized as serious pathogens for over a century and are the etiological agent of a variety of diseases ranging from mild cutaneous infections to often fatal forms of septic arthritis, endocarditis, toxic shock syndrome and sepsis. Despite intensive efforts to halt their spread, they remain the most common cause of community- and nosocomially acquired bacteremia. Murine models of Staphylocococus aureus-mediated arthritis and sepsis exist and are being used to gain a better understanding of the host-bacterium relationship as well to develop better methods of prevention and treatment.

Understanding choice of milk and bread for breakfast among Swedish children aged 11-15 years: an application of the Theory of Planned Behaviour.

The present study examined the influences of attitudes, social norms, perceived control and underlying beliefs on 11 to 15-year-olds' breakfast choices of milk with different fat content and high-fibre bread. All pupils in the 5th, 7th and 9th grades in Mölndal community (N=1730), Sweden, were asked to complete a questionnaire based on the Theory of Planned Behaviour. Two weeks later, they were asked to fill in a 7-day record of food consumed for breakfast. Consumption of milk and high-fibre bread was predicted from intentions, and for milk also by perceived behavioural control. Intentions were influenced by attitudes, perceptions of significant others' preferences, and perceived control. In addition, perception of the parents' consumption (descriptive norm) of the specific food played an important role. Attitudes, norms and perceived control predicted intentions to a similar extent in each age group. Attitudes to the consumption of milk and high fibre bread were influenced by beliefs about their sensory and health aspects. Females and the oldest children had greater knowledge about the healthier alternatives and the oldest children had a tendency to choose healthier options.

Sources of bias in a dietary survey of children.

OBJECTIVE: To compare non-responders and responders to a dietary survey with respect to demographic variables and intention to choose selected breakfast foods, and to examine if there was any systematic change in number of food items reported during a 7 d recording period. DESIGN: Cross-sectional survey. SETTING: Mölndal, Sweden. SUBJECTS: All pupils in 5th, 7th and 9th grades in the municipality were asked to complete a questionnaire during school hours. All those present (n = 1584, 92% of total) answered questions about lifestyle factors and about intentions, attitudes and beliefs concerning high-fibre bread and milk with varying fat content. All subjects in the initial sample were asked to fill in a 7 d record of food consumed. Acceptable food records were completed by 69% of the initial participants. RESULTS: Subjects not completing the food record differed significantly from participants with respect to demographic, lifestyle and dietary factors. Dropout was more common among those who reported not usually eating breakfast and among those intending to drink whole milk for breakfast. A decline in reported food items during the recording period was also observed. CONCLUSIONS: Two sources of bias were observed here, one indicating significant differences between non-participants and participants, the other suggesting the presence of a time-dependent trend in number of recorded foods. It is likely such biases are present in other dietary surveys involving schoolchildren, and should be taken into consideration in the design, analysis and interpretation of such studies.

Assessing food choice in school children: reliability and construct validity of a method stacking food photographs.

A method utilizing pictures was used to assess food choice with 44 school boys in three different age groups (10, 13 and 16 years old). The aim of the study was to test reliability and construct validity (i.e. inter-instrument agreement) of food choice assessed when the boys were asked to compose breakfasts. The focus was on choices of milk, margarine, bread and breakfast cereals, as in these food groups it is possible to choose between low-fat/high-fat and low-fibre/high-fibre products. Subjects were asked to repeat their composing of breakfasts after eight weeks, and to complete a four-day food record on breakfasts after the second interview occasion. For comparisons between food choices a new non-parametric statistical method was used. Both reliability and construct validity were good for choices of milk and margarine. The unreliability could be explained as random in nature or in terms of healthier choices in the second interview.

Human immunoglobulin isotype and IgG subclass response to different antigens of Moraxella catarrhalis.

Enzyme immunoassays were tested for the determination of antibodies of different isotypes and IgG subclasses to Moraxella catarrhalis in human sera. An assay based on an outer membrane protein preparation (OMP) as antigen was compared to assays using whole bacterial cells and a purified lipopolysaccharide preparation. There was a good correlation between the results obtained with the OMP preparation and the whole-cell antigen. In paired sera, optimal sensitivity was obtained by using the OMP preparation as coating antigen and testing for a rise in IgG3 antibodies. However, patients with high levels of antibodies in acute serum had no or only an insignificant antibody response during infection.

A case of Plesiomonas shigelloides cellulitis and bacteraemia from northern Europe.

Bacteremia caused by Plesiomonas shigelloides is a rare event, often associated with consumption of seafood and fresh or estuarine water in temperate or tropical climates. Most patients have showed underlying health disorders. Here we present a case of P. shigelloides septicaemia and cellulitis of the left hand associated with fish handling in Northern Sweden (65 degrees latitude north). The patient, who suffered from multiple myeloma, recovered uneventfully after initial treatment with intravenous cefuroxime followed by a course of oral ciprofloxacin. P. shigelloides seems to be ubiquitous in freshwater world-wide and may cause invasive infections also in cold climate areas.

Lack of serotype-specific antibody response to lipopolysaccharide antigens of Moraxella catarrhalis during lower respiratory tract infection.

An enzyme immunoassay (EIA) was used to determine the antibody response to different serotypes of lipopolysaccharide (LPS) antigens of Moraxella catarrhalis in adult patients with lower respiratory tract infections (LRTI). Moraxella catarrhalis was isolated from sputum or nasopharyngeal samples from 20 patients with LRTI. Sixteen of the isolates were serotype A, four were type B and none were type C. The antibody response to the different LPS serotypes was determined in paired sera from patients suffering from LRTI. In addition to the 20 patients with Moraxella catarrhalis isolated (Group 1), a group of seven patients with LRTI of unknown etiology (Group 2) and a group of ten patients with LRTI of known other bacterial etiology (Group 3) were selected for this study. An increase in antibody levels of > 1.5-fold (convalescent-/acute-phase serum) was recorded in approximately half of the patients, not only in the first group (Moraxella catarrhalis isolated) but also in the other two groups. However, in the first and second groups there was a correlation between an increase in antibody levels in the LPS EIA and in an EIA using whole bacterial cells as antigen. In the group of patients in whom Moraxella catarrhalis was isolated, the antibody response to LPS antigens was not serotype specific. The antibody response to type-A and type-B LPS was more predominant than the response to type-C LPS in most patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Delmopinol interactions with cell walls of gram-negative and gram-positive oral bacteria.

The main purpose of the present study was to investigate the influence of delmopinol hydrochloride on the cell surface morphology of gram-negative and gram-positive bacterial cells by using transmission electron microscopy. A second purpose was to evaluate the extraction of cell wall material caused by delmopinol and the binding of radiolabelled delmopinol to the various strains. Fresh isolates and type strains of gram-negative rods associated with periodontal disease, Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus actinomycetemcomitans, and strains of the gram-positive streptococci Streptococcus sanguis, Streptococcus mutans and Streptococcus salivarius, were exposed to 3.2 mM (0.1%) or 6.4 mM (0.2%) delmopinol hydrochloride from 1 to 90 min. For electron microscopy the cells were fixed and negatively contrast-stained. Treatment with 6.4 mM delmopinol for 1 min resulted in marked ultrastructural changes of cell wall components and the outer cell membrane of the 3 gram-negative species compared with control cells, whereas the gram-positive streptococci treated with delmopinol showed little or no morphologic alteration as compared with untreated cells. The result from the electron microscopy was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of proteins released from bacterial cells treated as for electron microscopy. More material was extracted from the gram-negative rods than from the gram-positive cocci. Significantly more delmopinol bound to the gram-negative rods than to the streptococci. It appears that the amphiphilic properties of delmopinol make gram-negative rods more vulnerable to delmopinol than gram-positive streptococci.

Significance of isolation of Moraxella catarrhalis in routine cultures from the respiratory tract in adults: antibody response studied in a whole cell EIA.

The significance of the isolation of Moraxella catarrhalis from sputum or nasopharynx was studied in patients treated at an infectious disease clinic. A whole-cell enzyme immunoassay was used to detect a specific antibody response to M. catarrhalis during infection. In all, 27 patients with respiratory tract infections and 4 with other infections were studied. Titre rises were recorded in 11/23 patients with lower respiratory tract infections, whereas patients with common cold or infections elsewhere all had negative serology. In patients with acute bronchitis, 7/10 patients responded with a significant titre rise. Patients with a low titre in their acute serum sample were those who responded with a titre increase during infection. The findings indicate that isolation of M. catarrhalis from sputa and nasopharyngeal samples in adults is of value for the etiological diagnosis of acute bronchitis and other lower respiratory tract infections, and is therefore important for the choice of drug for treatment, as many isolates are resistant to beta-lactam antibiotics.

Serological cross-reactions between Moraxella (Branhamella) catarrhalis and other oropharyngeal bacteria.

Oropharyngeal bacteria belonging to different species were tested for serological cross-reactions with Moraxella catarrhalis using sera from immunized rabbits. Sera were tested using immunofluorescence, an enzyme immunoassay (EIA) and immunoblotting. On immunofluorescence, significant cross-reactions were demonstrated with beta-hemolytic streptococci group A and group G, as well as with streptococci of the viridans group. Some cross-reactions were also noted with Neisseria meningitidis. In the EIA, strong cross-reactions were demonstrated with beta-hemolytic streptococci. No cross-reactions were obtained with Streptococcus pneumoniae, Haemophilus influenzae or common oral Neisseria. The results are of importance for the interpretation of serological tests to detect infections with Moraxella catarrhalis, and for the development of methods for detection of antigens in samples from the respiratory tract.

Variability of surface-exposed antigens of different strains of Moraxella catarrhalis.

For serological diagnosis of infection with Moraxella (Branhamella) catarrhalis it is important to determine if there is variability of antigenic properties among different strains. Cross-reactions of nine strains were investigated by an immunofluorescence test using sera from immunized rabbits. All titres but one were 1:256 or higher, the highest being 1:4096. Thus a high degree of antigenic similarity was demonstrated among different strains of Moraxella catarrhalis. However, the homologous titres of six sera were 2 to 16 times higher than the titres for other strains indicating strain variations in antigenic properties of some surface components. There was no correlation between lipopolysaccharide type and titre in the immunofluorescence test.

Minimal criteria for identification of Moraxella (Branhamella) catarrhalis.

A study was performed which aimed at testing the reliability of our routine diagnostic tests for identification of Moraxella (Branhamella) catarrhalis in clinical samples from the respiratory tract. A preliminary diagnosis of 122 isolates as Moraxella catarrhalis was obtained by using colony morphology and results of Gram stain and oxidase test as the sole diagnostic criteria. By using additional tests we could show that the preliminary diagnosis was incorrect for 21 isolates, which were classified as different Neisseria species. 20 of these were isolated from sputum samples. We propose that at least a test for DNA hydrolysis should be included in the routine procedure for identification of Moraxella catarrhalis in sputum.

Tolerance during inhalation of organic solvents.

Inhalation of several different halogenated solvents stimulated motor activity in mice. During prolonged exposure acute tolerance developed. The development of tolerance depended both on the schedule of exposure, and on the solvent. Exposure to trichloroethylene induced both stimulation and tolerance while the same degree of stimulation induced by 1,1,1-trichloroethane caused no tolerance. Thus the mechanisms which induce stimulation do not always initiate tolerance. Slow steady increases in the concentration of trichloroethylene could be maintained for several hours without any stimulation of motor activity. At the end of such exposures concentrations were reached which, if applied directly, would have induced considerable stimulation. Thus tolerance may develop without motor stimulation. Inhalation of ethanol also stimulated motor activity initially. During constant exposure the stimulation was followed by a considerable reduction in motor activity. This resulted in a hypoactive period, which in turn was followed by a second increase in motor activity, indicating the existence of not only two but several counteracting mechanisms. Development of metabolites with sedative effects counteracting the stimulating effect of the pure solvents seems to be one explanation for the results.