Sture Löfgren

Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study

Results from a previous longitudinal study, the Swedish OCTO-Immune study, indicated that the combination of higher CD8 peripheral blood lymphocytes (PBLs), decreased CD4 PBLs, and poor proliferative response to mitogenic stimulation in very old humans were associated with an increased 2 year mortality. In follow up studies this combination of immune parameters was significantly associated with a CD4/CD8 ratio less than one and positive IgG serologic titers to cytomegalovirus (CMV). The present study, the Swedish NONA-Immune study, was an extension of that study, using a new sample of the very old. The results of this study confirmed the results of the previous study and extended the surface marker profile of the PBLs, indicating that the CD4/CD8 ratio change is associated with increased CD8 cells, decreased CD4 cells, and lymphocyte activation. The predominant phenotypes of the CD3+CD8+ cells were CD27-, CD28-, CD56+, and CD57+, CD45RA+, and double marked CD45RA+RO+. As in the OCTO study, the NONA-Immune data indicated that the changes are associated significantly with seropositive responses to CMV.

Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old: the Swedish longitudinal OCTO immune study

Results from the previous times (Times 1-3) of the Swedish longitudinal OCTO immune study indicated that a combination of high CD8 and low CD4 percentages and poor T-cell proliferation in PBL was associated with a higher 2-year mortality in a sample of very old Swedish individuals. The combination of immune parameters was closely related to an inverted CD4/CD8 ratio. In the present study at Time 4 (T4) results are reported from the final follow-up of this longitudinal study, 8 years after it was initiated in 1989. An additional goal at this time point was to examine the immune system alterations in the very old in relation to evidence of lymphocyte activation and cytomegalovirus antibody status. In the present study immune system changes were identified that suggest a loss of T-cell homeostasis, as reflected by a decrease in the number of CD4 cells and a very significant increase in the number of CD8 cells in individuals with an inverted CD4/CD8 ratio. When considered over the duration of the OCTO study the inversion occurred in a high percentage (32%) of the individuals included in the original sample and was associated with non-survival. At T4 the changes were apparent in a number of the T-cell subsets, but particularly in the CD8+CD28-and CD57+ subsets. T-cell activation was significantly associated with the inversion of the CD4/CD8 ratio. In this very old sample the subset alterations were associated with evidence of cytomegalovirus (CMV) infection.

Identification of unique gene expression patterns within different lesional sites of keloids

Keloid disease is a significant clinical problem, especially in black populations, with an estimated incidence of 4–16%. Keloids are fibroproliferative dermal tumors developing as a result of deregulated wound healing. The dynamic nature of keloids is illustrated by clinical regression in the center, while the margin remains active growing into the surrounding healthy skin. Therefore, the gene expression profiles of fibroblasts from different sites of the keloids were characterized using Affymetrix microarrays covering the whole human genome. This study revealed 105 genes that were differentially regulated (79 genes were up‐regulated and 26 down‐regulated) in a unique gene expression profile in different sites of keloids where progression or regression of the process was in progress. The apoptosis inhibitor AVEN was found to be up‐regulated at the active margin of keloids, while apoptosis‐inducing genes such as ADAM12 and genes inducing extracellular matrix (ECM) degradation such as matrix metalloproteinase‐19 were up‐regulated in the regressing keloid center. We identified genes previously not described in the development of keloids. Activating proapoptotic genes or inhibiting ECM‐inducing genes as INHBA or monocyte chemoattractant protein‐1 might be possible target genes for new treatment strategies for keloid disease.

Methicillin-resistant Staphylococcus aureus (MRSA) in municipal wastewater: an uncharted threat?

Aims:  (i) To cultivate methicillin‐resistant Staphylococcus aureus (MRSA) from a full‐scale wastewater treatment plant (WWTP), (ii) To characterize the indigenous MRSA‐flora, (iii) To investigate how the treatment process affects clonal distribution and (iv) To examine the genetic relation between MRSA from wastewater and clinical MRSA.

Erythromycin treatment is beneficial for longstanding Moraxella catarrhalis associated cough in children.

The benefits of antibiotic treatment and a nasopharyngeal culture in children with longstanding cough were analysed in a prospective randomized open study. Clinically suspected pertussis was excluded. Of 40 children given erythromycin for 7 days, 35 (88%) recovered in one week, compared with 17/47 (36%) untreated (p < 0.0001). Erythromycin eliminated Moraxella catarrhalis from the nasopharynx in 21/31 children (68%), compared with spontaneous disappearance in 7/35 (20%) untreated controls (p < 0.001). Purulent bronchitis or otitis media occurred in 2 children (5%) in the treatment group and in 21 (45%) in the control group (p < 0.01). To evaluate the clinical role of isolated pathogens, the 47 untreated subjects were studied. Seven of 35 children harbouring M. catarrhalis recovered, compared with 8/12 in whom this bacterium was absent (p < 0.01). No correlation was found between the isolation of Haemophilus influenzae or Streptococcus pneumoniae and the clinical outcome. Children with persistent cough > 10 days may benefit from erythromycin treatment. M. catarrhalis in the nasopharynx indicates prolonged symptoms and increased risk of bacterial complications.

Infection of Human Endothelial Cells with Staphylococcus aureus Induces Transcription of Genes Encoding an Innate Immunity Response

Staphylococcus aureus is a gram‐positive bacterium frequently isolated from patients with bloodstream infections. Endothelial cells (EC) play an important role in host defence against bacteria, and recent reports have shown that infection of EC with S. aureus induces expression of cytokines and cell surface receptors involved in activating the innate immune response. The ability of S. aureus to invade nonphagocytic cells, including EC, has been documented. However, the knowledge of the role of EC in pathogenesis of S. aureus infection is still limited. In this study, we investigate the gene‐expression program in human EC initiated by internalized S. aureus, using microarray analysis. We found 156 genes that were differentially regulated at least threefold, using arrays representing 14,239 genes. Many of the upregulated genes code for proteins involved in innate immunity, such as cytokines, chemokines and cell adhesion proteins. Other upregulated genes encode proteins involved in antigen presentation, cell signalling and metabolism. Furthermore, intracellular bacteria survived for days without inducing EC death.

Asymptomatic bacteriuria in the elderly: High prevalence and high turnover of strains

Asymptomatic bacteriuria (ASB) was followed in repeated prevalence surveys in a cohort of non-institutionalized residents (n=330), aged≥80 y. Urine samples were collected at baseline, and at 6, and at 18 months. Phenotyping (PhenePlate) was performed on isolates of Escherichia coli to evaluate strain relatedness. ASB occurred in 19.0, 19.4, and 19.9% in women, and in 9.4, 9.6 and 7.9% in men, at baseline and at the 6- and 18-months follow-up, respectively, and ASB was found at least once in 37% of women and in 20% of men. Of those with ASB at baseline, 60% also had ASB in the 2 subsequent surveys. Among those with persisting E. coli bacteriuria, 76% and 40%, respectively, carried the same strain at the 6- and 18-months follow-ups. In women, we found that the risk of developing a symptomatic urinary tract infection within 24 months was higher among those with ASB at baseline than in those without bacteriuria (p=0.019). ASB is common and often persistent, but we found a high turnover of strains, indicating a high rate of recolonization.

An outbreak of Legionnaires' Disease in a Swedish Hospital

We report a nosocomial outbreak of Legionella pneumophila serogroup (sg) 1 infection at the general hospital, Värnamo, Sweden. From December 1990 to February 1991, 28 patients and 3 staff fell ill with pneumonia and 3 died. L. pneumophila sg 1 together with several other Legionellae were isolated from the hot water supply to 17 of 20 hospital wards, probably being spread by aerosolization via shower nozzles. Raising the hospitals hot water temperature from 45 degrees C to 65 degrees C, together with heat disinfection of the shower equipment, arrested the outbreak within a week. Keeping the hot water temperature > or = 60 degrees C without chlorination eliminated L. pneumophila from > 75% of the wards. During a period of 2 years after the outbreak we have diagnosed only 1 case of nosocomial legionellosis at the hospital despite an active surveillance program.

Cytokines in urine in elderly subjects with acute cystitis and asymptomatic bacteriuria

Objective. Searching for useful diagnostic tools to discriminate between asymptomatic bacteriuria (ASB) and acute cystitis, this study compared urinary levels of cytokines/chemokines and leukocyte esterase in three groups of elderly subjects; those with acute cystitis, those with ASB, and those without bacteriuria. Design. Comparative laboratory. Setting. Primary care. Subjects. A total of 16 patients with acute cystitis, 24 subjects with ASB, and 20 controls without bacteriuria, all of whom were aged 80 or over. Main outcome measures. Urinary levels of IL-1β, TNF-α, IL-12, IL-18, CXCL1 (GRO-α), CXCL8 (IL-8), CCL2 (MCP-1), IL-6, IL-10, and leukocyte esterase. Results. Urinary levels of CXCL1, CXCL8, and IL-6 were significantly higher in acute cystitis patients than in the ASB group. The sensitivities and specificities for CXCL8, IL-6, and leukocyte esterase to discriminate between acute cystitis and ASB were 63% (95% CI 36–84) and 96% (95% CI 77–100) (cut-off > 285 pg/mg creatinine), 81% (95% CI 54–95) and 96% (95% CI 77–100) (cut-off > 30 pg/mg creatinine), and 88% (95% CI 60–98) and 79% (95% CI 57–92) (cut-off > 2, on a scale of 0–4), respectively. Conclusions. The results indicate that measurement of urinary cytokines, and also leukocyte esterase, when using a cut-off value > 2, could be useful in clinical practice to discriminate between symptomatic and asymptomatic urinary tract infections in the elderly. A combination of IL-6 and leukocyte esterase could be even more useful. This needs to be evaluated in prospective studies on the diagnosis and treatment of urinary tract infections in an elderly population.

DNA promoter methylation status and protein expression of interleukin-8 in human colorectal adenocarcinomas

BackgroundInterleukin-8 (IL-8) also referred to as CXCL8, a member of the CXC chemokine family that attracts neutrophils and other leukocytes, has been associated with cancer. Angiogenesis is a prime regulator of tumour expansion and data support that IL-8 is a potent angiogenic factor. Epigenomic instability has been postulated to play a role for the development of multiple neoplasias including colorectal cancer (CRC). DNA methylation of cytosine residues in CpG dinucleotides leads to transcriptional silencing of associated genes.MethodIn this study, we comparatively analysed the protein expression of IL-8 in plasma, tumour and paired normal tissue and methylation status of the IL-8 gene to evaluate its impact on CRC.ResultsCollectively, by using Luminex technology, we noted a significantly higher IL-8 level in cancer tissue compared to paired normal tissue and that CRC patients exhibit significantly higher plasma levels than healthy controls. Analysed by methylation-specific polymerase chain reaction, we detected IL-8 hypomethylation in 64% of the cancerous tissue cases but no hypomethylation was found in paired normal tissue. We noted that the CRC patients with IL-8 hypomethylation revealed a significant higher level of IL-8 protein in cancerous tissue, which tended to be associated with distant metastasis. We also observed that patients with distant metastasis showed a significantly higher plasma level of IL-8 in relation to patients without distant metastasis.ConclusionOur results suggest that the predominance of high plasma levels of IL-8 in patients with distant metastasis in combination with the hypomethylation of the IL-8 promoter region might be a useful marker of the disease advancement.