Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix.

http://www.jbc.org/content/254/19/9933.full.pdf

Laminin--a glycoprotein from basement membranes.

Bacteria belonging to the genus Klebsiella frequently cause human nosocomial infections. In particular, the medically most important Klebsiella species, Klebsiella pneumoniae, accounts for a significant proportion of hospital-acquired urinary tract infections, pneumonia, septicemias, and soft tissue infections. The principal pathogenic reservoirs for transmission of Klebsiella are the gastrointestinal tract and the hands of hospital personnel. Because of their ability to spread rapidly in the hospital environment, these bacteria tend to cause nosocomial outbreaks. Hospital outbreaks of multidrug-resistant Klebsiella spp., especially those in neonatal wards, are often caused by new types of strains, the so-called extended-spectrum-β-lactamase (ESBL) producers. The incidence of ESBL-producing strains among clinical Klebsiella isolates has been steadily increasing over the past years. The resulting limitations on the therapeutic options demand new measures for the management of Klebsiella hospital infections. While the different typing methods are useful epidemiological tools for infection control, recent findings about Klebsiella virulence factors have provided new insights into the pathogenic strategies of these bacteria. Klebsiella pathogenicity factors such as capsules or lipopolysaccharides are presently considered to be promising candidates for vaccination efforts that may serve as immunological infection control measures.

/pdf/klebsiella-spp-as-nosocomial-pathogens-epidemiology-taxonomy-1qbzenizx4.pdf

Klebsiella spp. as Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors

ContextEvaluation of trends in organ dysfunction in critically ill patients
may help predict outcome.ObjectiveTo determine the usefulness of repeated measurement the Sequential Organ
Failure Assessment (SOFA) score for prediction of mortality in intensive care
unit (ICU) patients.DesignProspective, observational cohort study conducted from April 1 to July
31, 1999.SettingA 31-bed medicosurgical ICU at a university hospital in Belgium.PatientsThree hundred fifty-two consecutive patients (mean age, 59 years) admitted
to the ICU for more than 24 hours for whom the SOFA score was calculated on
admission and every 48 hours until discharge.Main Outcome MeasuresInitial SOFA score (0-24), Δ-SOFA scores (differences between
subsequent scores), and the highest and mean SOFA scores obtained during the
ICU stay and their correlations with mortality.ResultsThe initial, highest, and mean SOFA scores correlated well with mortality.
Initial and highest scores of more than 11 or mean scores of more than 5 corresponded
to mortality of more than 80%. The predictive value of the mean score was
independent of the length of ICU stay. In univariate analysis, mean and highest
SOFA scores had the strongest correlation with mortality, followed by Δ-SOFA
and initial SOFA scores. The area under the receiver operating characteristic
curve was largest for highest scores (0.90; SE, 0.02; P<.001 vs initial score). When analyzing trends in the SOFA score
during the first 96 hours, regardless of the initial score, the mortality
rate was at least 50% when the score increased, 27% to 35% when it remained
unchanged, and less than 27% when it decreased. Differences in mortality were
better predicted in the first 48 hours than in the subsequent 48 hours. There
was no significant difference in the length of stay among these groups. Except
for initial scores of more than 11 (mortality rate >90%), a decreasing score
during the first 48 hours was associated with a mortality rate of less than
6%, while an unchanged or increasing score was associated with a mortality
rate of 37% when the initial score was 2 to 7 and 60% when the initial score
was 8 to 11.ConclusionsSequential assessment of organ dysfunction during the first few days
of ICU admission is a good indicator of prognosis. Both the mean and highest
SOFA scores are particularly useful predictors of outcome. Independent of
the initial score, an increase in SOFA score during the first 48 hours in
the ICU predicts a mortality rate of at least 50%.

https://jamanetwork.com/journals/jama/articlepdf/194262/JCE00056.pdf

Serial evaluation of the SOFA score to predict outcome in critically ill patients.

Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

Invasive bacterial pathogens intervene at various stages and by various mechanisms with the mammalian plasminogen/plasmin system. A vast number of pathogens express plasmin(ogen) receptors that immobilize plasmin(ogen) on the bacterial surface, an event that enhances activation of plasminogen by mammalian plasminogen activators. Bacteria also influence secretion of plasminogen activators and their inhibitors from mammalian cells. The prokaryotic plasminogen activators streptokinase and staphylokinase form a complex with plasmin(ogen) and thus enhance plasminogen activation. The Pla surface protease of Yersinia pestis resembles mammalian activators in function and converts plasminogen to plasmin by limited proteolysis. In essence, plasminogen receptors and activators turn bacteria into proteolytic organisms using a host-derived system. In Gram-negative bacteria, the filamentous surface appendages fimbriae and flagella form a major group of plasminogen receptors. In Gram-positive bacteria, surface-bound enzyme molecules as well as M-protein-related structures have been identified as plasminogen receptors, the former receptor type also occurs on mammalian cells. Plasmin is a broad-spectrum serine protease that degrades fibrin and noncollagenous proteins of extracellular matrices and activates latent procollagenases. Consequently, plasmin generated on or activated by Haemophilus influenzae, Salmonella typhimurium, Streptococcus pneumoniae, Y. pestis, and Borrelia burgdorferi has been shown to degrade mammalian extracellular matrices. In a few instances plasminogen activation has been shown to enhance bacterial metastasis in vitro through reconstituted basement membrane or epithelial cell monolayers. In vivo evidence for a role of plasminogen activation in pathogenesis is limited to Y. pestis, Borrelia, and group A streptococci. Bacterial proteases may also directly activate latent procollagenases or inactivate protease inhibitors of human plasma, and thus contribute to tissue damage and bacterial spread across tissue barriers.

Bacterial plasminogen activators and receptors

Fibroblast surface antigen: a new serum protein.

Objective. To evaluate the performance of procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein, leukocyte count, D-dimer, and antithrombin III at onset of septic episode and 24 h later in prediction of hospital mortality in critically ill patients with suspected sepsis.

Predictive value of procalcitonin and interleukin 6 in critically ill patients with suspected sepsis

The attachment of Staphylococcus aureus (Cowan I) and two strains of group A and G streptococci on glass cover slips coated with fibronectin, fibronectin fragments, or fibrinogen was studied. The attachment was quantitated by counting the attached bacteria on glass surfaces coated with a similar molarity of the proteins. Fibronectin was a more effective attachment factor than fibrinogen for staphylococci, while group G streptococci attached better on fibrinogen- than on fibronectin-coated cover slips. In this system, group A streptococci bound almost exclusively to substrate-bound fibrinogen. Attachment experiments involving the use of staphylococci pretreated with soluble fibronectin or fibrinogen revealed that bacterium-bound fibronectin and fibrinogen were able to enhance the adherence on cover slips coated with fibronectin. The 30-kilodalton NH2-terminal and the 120- to 140-kilodalton COOH-terminal fragments of fibronectin, both of which contain bacterial binding sites, mediated the staphylococcal attachment, suggesting that both parts of the molecule are involved in the attachment mediated by fibronectin.

https://iai.asm.org/content/iai/50/1/77.full.pdf

Attachment of staphylococci and streptococci on fibronectin, fibronectin fragments, and fibrinogen bound to a solid phase.

Serum CA 19-9 antigen concentrations were measured in 246 patients with benign and histologically confirmed malignant gastrointestinal diseases. The CA 19-9 concentration was above the upper limit of the normal range (0-37 U/ml) in 76% of patients with pancreatic carcinoma, 73% of patients with cholangiocarcinoma, 42% of patients with gastric carcinoma, and 22% of patients with hepatoma. High CA 19-9 concentrations were found mainly in patients with a metastasised cancer, whereas 71% of patients with a localised carcinoma had normal CA 19-9 concentrations. All of the patients with benign gastric diseases had normal CA 19-9 values. Moderately increased concentrations were found in 15-36% of the patients with benign pancreatic, liver, and biliary tract diseases. alpha-fetoprotein was a better marker for hepatomas than CA 19-9. CA 19-9 was better than carcinoembryonic antigen in differentiating malignant from benign diseases. The results indicate that the CA 19-9 assay is not completely specific for cancer but serves as a valuable adjunct, especially in the diagnosis of pancreatic carcinoma.

https://jcp.bmj.com/content/jclinpath/37/2/218.full.pdf

Pentti Kuusela

Papers

Bacterial plasminogen activators and receptors

Fibroblast surface antigen: a new serum protein.

Predictive value of procalcitonin and interleukin 6 in critically ill patients with suspected sepsis

Attachment of staphylococci and streptococci on fibronectin, fibronectin fragments, and fibrinogen bound to a solid phase.

Comparison of a new tumour marker, CA 19-9, with alpha-fetoprotein and carcinoembryonic antigen in patients with upper gastrointestinal diseases