182 results on '"Heikki Repo"'
Search Results
102. Aberrant TNF secretion by whole blood in healthy subjects with a history of reactive arthritis: time course in adherent and non‐adherent cultures
- Author
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Heikki Repo, Arto Orpana, Krista Anttonen, and Marjatta Leirisalo-Repo
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Lipopolysaccharides ,Male ,Lipopolysaccharide ,Lipopolysaccharide Receptors ,Arthritis ,Monocytes ,chemistry.chemical_compound ,0302 clinical medicine ,Immunology and Allergy ,Medicine ,skin and connective tissue diseases ,Calcimycin ,Cells, Cultured ,HLA-B27 Antigen ,Whole blood ,0303 health sciences ,Middle Aged ,3. Good health ,Extended Report ,medicine.anatomical_structure ,Tumor necrosis factor alpha ,Female ,musculoskeletal diseases ,Adult ,medicine.medical_specialty ,Genotype ,Yersinia Infections ,CD14 ,Immunology ,Arthritis, Reactive ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Rheumatology ,Internal medicine ,Prohibitins ,Cell Adhesion ,Humans ,030304 developmental biology ,Aged ,business.industry ,Tumor Necrosis Factor-alpha ,Monocyte ,medicine.disease ,Endocrinology ,chemistry ,TLR4 ,Phorbol ,business ,030215 immunology - Abstract
The pathogenesis of reactive arthritis (ReA) apparently involves aberrations in innate immune functions such as monocyte tumour necrosis factor (TNF) generation.To investigate TNF production in healthy subjects with previous yersinia triggered reactive arthritis.The study comprised HLA-B27 positive subjects with previous reactive arthritis (B27+ReA+), and B27+ReA- and B27-ReA- subjects (n = 15 each). Whole blood TNF production was induced by lipopolysaccharide (LPS), which binds to CD14/TLR4 on the monocyte surface, or by a combination of phorbol 12-myristate 13-acetate (PMA) and Ca(2+) ionophore A23187, which activates monocytes independently of cell surface receptors. To further evaluate the possible role of adhesion mediated signalling on TNF production, blood samples were incubated in adherent or non-adherent conditions. TNF levels in culture supernatants were measured using an automated immunoassay analyser. The CD14(-159)C/T genotype was determined by a cycle minisequencing method.B27+ReA+ supernatants had higher TNF levels than B27+ReA- supernatants in PMA/A23187 wells in two hour (p = 0.004) and four hour cultures (p = 0.001). Rapid initial TNF release took place in adherent but not in non-adherent conditions. This adhesion associated difference was greater in the B27+ReA+ group than in the B27+ReA- or B27-ReA- group in response to PMA/A23187 (p values0.001), and greater in the B27+ReA+ group than in the B27-ReA- group in response to LPS (p = 0.021). CD14(-159)T was associated allele dose dependently with an increase in the LPS induced TNF secretion allele (p = 0.030).who have recovered from yersinia arthritis show enhanced TNF production, which may be regulated at the level of monocyte adhesion.
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- 2005
103. Low circulating soluble interleukin 2 receptor level predicts rapid response in patients with refractory rheumatoid arthritis treated with infliximab
- Author
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Heikki Repo, Hannu Kautiainen, Marjatta Leirisalo-Repo, Antti Kuuliala, and R. Nissinen
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musculoskeletal diseases ,Adult ,Male ,medicine.medical_specialty ,Immunology ,Lymphocyte Activation ,Gastroenterology ,Severity of Illness Index ,General Biochemistry, Genetics and Molecular Biology ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Refractory ,Internal medicine ,Severity of illness ,medicine ,Immunology and Allergy ,Humans ,skin and connective tissue diseases ,030304 developmental biology ,Aged ,030203 arthritis & rheumatology ,Autoimmune disease ,0303 health sciences ,business.industry ,Antibodies, Monoclonal ,Receptors, Interleukin-2 ,Middle Aged ,medicine.disease ,Connective tissue disease ,Infliximab ,Confidence interval ,3. Good health ,Surgery ,Extended Report ,Treatment Outcome ,Rheumatoid arthritis ,Antirheumatic Agents ,Drug Therapy, Combination ,Female ,business ,Biomarkers ,medicine.drug - Abstract
Treatment with infliximab induces a rapid therapeutic response in most patients with active rheumatoid arthritis. Factors predicting good response are not well known.To study the predictive value of baseline level of soluble interleukin 2 receptor (sIL2R), a marker of lymphocyte activation, on the treatment response.24 patients with active rheumatoid arthritis received intravenous infusions of infliximab at study entry, at two weeks, at six weeks, and at eight week intervals thereafter. Outcome was evaluated at six weeks and 22 weeks. Clinical assessment and standard laboratory tests were made and the DAS28 disease activity score was calculated. Serum sIL2R level at entry was measured by automated immunoassay analyser (Immulite). The mean change in DAS28 score from entry to six weeks and 22 weeks was calculated and related to sIL2R level using baseline adjusted robust regression analysis.Baseline level of serum sIL2R (mean (SD), 621 (325) U/ml) did not correlate with baseline DAS28 score (r = 0.24 (95% confidence interval, -0.18 to 0.58)). At six weeks DAS28 scores improved, with a mean change of -2.53 (-3.08 to -1.98) (p0.001). This change was predicted by low baseline sIL2R level (regression coefficient per 100 U/ml: 0.205 (0.003 to 0.407) (p = 0.047)). At 22 weeks the DAS28 scores improved, with a mean change of -2.26 (-2.75 to -1.77) (p0.001). The change was not predicted by baseline sIL2R level.Low baseline sIL2R level may predict a rapid clinical response in patients with refractory rheumatoid arthritis treated with infliximab.
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- 2005
104. Granulocyte colony-stimulating factor therapy and systemic inflammation in critically ill patients
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H. Kautiainen, Heikki Repo, Annika Takala, O. Takkunen, Esa Rintala, and Ville Pettilä
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Adult ,Male ,medicine.medical_specialty ,Critical Illness ,Immunology ,Filgrastim ,Granulocyte ,Systemic inflammation ,Placebo ,Gastroenterology ,Endothelial activation ,Internal medicine ,Granulocyte Colony-Stimulating Factor ,medicine ,Humans ,Aged ,Pharmacology ,Inflammation ,business.industry ,Interleukin ,Middle Aged ,Rheumatology ,Granulocyte colony-stimulating factor ,Blood Cell Count ,medicine.anatomical_structure ,Female ,medicine.symptom ,business ,Biomarkers ,medicine.drug - Abstract
Objective and design: The effect of the granulocyte colony-stimulating factor filgrastim on systemic inflammation was investigated in a prospective, randomized, placebo- controlled, double-blind study in critically ill patients. Subjects: 59 Critically ill patients were recruited within 48 h of intubation due to ventilatory insufficiency. Treatment: Subcutaneous dosage of placebo or 300 μg filgrastim once daily. Methods: Serum samples were collected at study entry, and 1 and 3 days after the start (Day1 and Day3, respectively). Levels of soluble E-selectin (sE-selectin) and interleukin(IL)-10 were determined by ELISA, and those of IL-6, and soluble IL-2 receptor (sIL-2R) by Immulite® chemiluminescence immunoassay. Results: The median sE-selectin level decreased by day 3 significantly in the control group but not in the filgrastim group. The difference in the change between the study groups was significant (p = 0.049). IL-10 levels decreased significantly in the filgrastim group, tended to decrease in controls (p = 0.052), and the difference in the change tended to be significant (p = 0.058). IL-6 levels decreased in both groups comparably. sIL-2R levels were elevated and stable. Conclusions: Filgrastim prolongs endothelial activation and possibly inhibits development of immune suppression mediated by IL-10.
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- 2005
105. The effect of albumin dialysis on cytokine levels in acute liver failure and need for liver transplantation
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Helena Isoniemi, Heikki Repo, Anna-Maria Koivusalo, Krister Höckerstedt, and Ilkka Ilonen
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Adult ,Time Factors ,Adolescent ,medicine.medical_treatment ,Multiple Organ Failure ,030232 urology & nephrology ,030204 cardiovascular system & hematology ,Pharmacology ,Liver transplantation ,Proinflammatory cytokine ,03 medical and health sciences ,0302 clinical medicine ,Albumins ,medicine ,Humans ,Interleukin 6 ,Dialysis ,Aged ,Aged, 80 and over ,Transplantation ,biology ,business.industry ,Albumin ,Interleukin ,Liver Failure, Acute ,Middle Aged ,Survival Analysis ,3. Good health ,Liver Transplantation ,Cytokine ,Immunology ,biology.protein ,Cytokines ,Surgery ,business - Abstract
In acute liver failure (ALF), detoxification capacity of liver cells is reduced and a variety of cytokines, immune modulators, and toxic substances are accumulating. Multiple organ failure in ALF has been associated with increased blood cytokine levels. We have used a blood purification system, molecular adsorbent recirculating system (MARS), which is based on removal of both protein bound and water-soluble substances and toxins in liver failure. In this study, we measured the effect of MARS therapy on plasma cytokine levels in 49 patients with ALF. Interleukin 6 (IL-6), IL-8, IL-10 and tumor necrosis factor (TNF)alfa were determined immediately before and after the first MARS therapy and after the last session using enzyme-linked immunosorbent assays. The overall survival of these ALF patients was 82% at 6 months; the native liver recovered in 26 cases, and 14 were successfully transplanted. All three interleukins were increased before the MARS treatment but only anti-inflammatory IL-10 was reduced significantly during therapy, which in this setting could be interpreted as a positive effect. We were not able to show constant decreases in proinflammatory cytokines, but only transient effects on IL-8 and IL-6. Surprisingly TNFalfa level was normal and did not change during therapy. In theory, MARS albumin dialysis may remove toxic substances from the blood circulation and thereby improve the possibilities of the liver to recover; however, of the measured cytokines only IL-10 decreased significantly.
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- 2005
106. Pancreatic secretory trypsin inhibitor (SPINK1) gene mutations in patients with acute pancreatitis
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Annukka Paju, Ulf-Håkan Stenman, Heli Nevanlinna, Pauli Puolakkainen, Heikki Repo, Esko Kemppainen, Eija Tukiainen, and Marja-Leena Kylänpää
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Adult ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Trypsin inhibitor ,Gastroenterology ,Severity of Illness Index ,Endocrinology ,Internal medicine ,Internal Medicine ,medicine ,SPINK1 Gene ,Humans ,Point Mutation ,Genetic Predisposition to Disease ,Gene ,Pancreatic Secretory Trypsin Inhibitor ,Aged ,Aged, 80 and over ,Hepatology ,business.industry ,Point mutation ,Middle Aged ,medicine.disease ,Pancreatitis ,Trypsin Inhibitor, Kazal Pancreatic ,Acute Disease ,Population study ,Acute pancreatitis ,Female ,business ,Carrier Proteins - Abstract
Mutations in the secretory trypsin inhibitor (SPINK1) gene have been found to be associated with hereditary and chronic pancreatitis. There are no previous reports on SPINK1 mutations in patients with acute pancreatitis (AP).The study population consists of 371 patients with AP, of which 207 patients had mild and 164 had a severe form of the disease. The etiologies of AP were identified. Four hundred fifty-nine blood donors served as controls. SPINK1 N34S and P55S mutations were detected by minisequencing and confirmed by direct sequencing.The N34S mutation was found in 29 (7.8%) of the patients and in 12 (2.6%) of the controls (P0.0001, Fisher exact test). There was no difference in the frequency of the P55SS mutation between the groups. A majority of the patients (n = 229; 61.7%) had alcohol-induced AP. The frequency of the N34S mutation was higher in the subgroups of severe AP (15/164; 9.1%) and alcohol-induced AP (21/229; 9.2%), but the differences were not statistically significant. No differences in age at admission and number of attacks of AP were observed between the groups.SPINK1 N34S mutation enhances the susceptibility of AP.
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- 2005
107. CARD15 frameshift mutation in patients with CROHN disease is associated with immune dysregulation
- Author
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Tiina Heliö, Maija Lappalainen, Ulla Turunen, Martti Färkkilä, Heikki Repo, Kimmo Kontula, Leena Halme, and Paulina Paavola-Sakki
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Adult ,Lipopolysaccharides ,Male ,CD14 ,Cell Culture Techniques ,Nod2 Signaling Adaptor Protein ,Biology ,medicine.disease_cause ,Peripheral blood mononuclear cell ,Inflammatory bowel disease ,Frameshift mutation ,03 medical and health sciences ,Interferon-gamma ,0302 clinical medicine ,Immune system ,Crohn Disease ,NOD2 ,medicine ,Humans ,Frameshift Mutation ,030304 developmental biology ,0303 health sciences ,Tumor Necrosis Factor-alpha ,Monocyte ,Gastroenterology ,Intracellular Signaling Peptides and Proteins ,Granulocyte-Macrophage Colony-Stimulating Factor ,Immune dysregulation ,Middle Aged ,medicine.disease ,digestive system diseases ,3. Good health ,Interleukin-10 ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Case-Control Studies ,Immunology ,Leukocytes, Mononuclear ,Female - Abstract
Mutations in the caspase-activating recruitment domain 15 (CARD15) gene are associated with Crohn disease (CD). CARD15 is an intracellular receptor for bacterial lipopolysaccharides (LPS). LPS-induced activation of transfectants containing the frameshift mutation (1007fs) of CARD15 is impaired. The aim of this study was to investigate whether the presence of CARD15 1007fs affects activation of CD patients' own cells. Patients (4 homozygotes, 6 heterozygotes, and 6 wild-type) were matched according to clinical picture and medication.Immune inflammatory status was evaluated by measuring monocyte HLA-DR and CD11b densities and the proportion of CD14dimCD16+ monocytes, and was found to be comparable in the three groups. Blood mononuclear cells were cultured overnight in serum-free medium alone, or the medium supplemented with LPS (0.1-10.0 ng/mL), a combination of IFN-gamma (100 IU/mL) and granulocyte-macrophage colony stimulating factor (GM-CSF) (5 ng/mL), or both. TNF and IL-10 levels in the culture supernatant were determined.LPS 0.1 or 1.0 ng/mL alone did not increase TNF levels. IFN-gamma/GM-CSF induced TNF release, and co-culture with LPS 1.0 or 10.0 ng/mL was strongly synergistic. CARD15 1007fs mutation was linked in a gene-dose-dependent manner to low TNF release induced by IFN-gamma/GM-CSF (P value for linear trend = 0.001). The degree of synergism in co-culture was normal or high, suggesting that 1007fs did not depress responses to LPS. IL-10 levels were not related to CARD15 1007fs.In CD patients, CARD15 1007fs is associated in a gene-dose-dependent manner to low mononuclear cell TNF release by IFN-gamma/GM-CSF but does not impair TNF release by LPS. This type of immune dysregulation may influence susceptibility to and/or phenotype of CD.
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- 2005
108. Laboratory markers of systemic inflammation as predictors of bloodstream infection in acutely ill patients admitted to hospital in medical emergency
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Heikki Repo, H. Kautiainen, Annika Takala, and H Aalto
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Adult ,Male ,Microbiology (medical) ,medicine.medical_specialty ,Adolescent ,Critical Illness ,Bacteremia ,Inflammation ,Systemic inflammation ,Risk Assessment ,Sensitivity and Specificity ,Sampling Studies ,Procalcitonin ,Cohort Studies ,Medical microbiology ,Predictive Value of Tests ,Internal medicine ,Blood-Borne Pathogens ,Confidence Intervals ,medicine ,Humans ,Survival rate ,Finland ,Aged ,Aged, 80 and over ,Interleukin-6 ,business.industry ,Interleukin-8 ,Receptors, Interleukin-2 ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Shock, Septic ,Survival Rate ,C-Reactive Protein ,Infectious Diseases ,ROC Curve ,Predictive value of tests ,Acute Disease ,Immunology ,Female ,medicine.symptom ,Emergency Service, Hospital ,business ,Biomarkers ,Cohort study - Abstract
The aim of the present study was to determine whether the presence of an infectious focus or of fever alone can predict bloodstream infection and whether levels of C-reactive protein, procalcitonin, interleukin (IL)-6, IL-8, and soluble IL-2 receptor (sIL-2R) improve the diagnosis of community-acquired bloodstream infection. Markers of systemic inflammation were studied in 92 patients with community-acquired infection. On admission to hospital, 54 patients had an infectious focus, 25 had fever without an infectious focus, and 13 had neither. The presence of focus or fever predicted bloodstream infection (n=13 patients) with a sensitivity of 100% (95% confidence interval, 75-100), a specificity of 16% (95%CI, 9-26), a negative predictive value of 100% (95%CI, 75-100), and a positive predictive value of 16% (95%CI, 9-26). Positive predictive values of C-reactive protein, procalcitonin, IL-6, IL-8, and sIL-2R, all measured on admission, were also low (33-44%). Eight febrile patients in whom an infectious focus was found during a 3-day follow-up period had higher on-admission IL-6 (P=0.005) and sIL-2R (P=0.046) levels than did 17 febrile patients without an infectious focus. In conclusion, markers of systemic inflammation do not improve the diagnosis of community-acquired bloodstream infection; however, they may aid in identifying patients with fever due to occult infection.
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- 2004
109. Cellular and humoral markers of systemic inflammation in acute reactive arthritis and early rheumatoid arthritis
- Author
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Antti Kuuliala, Sanna Siitonen, A Takala, Heikki Repo, and Marjatta Leirisalo-Repo
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Male ,Bacteremia ,Systemic inflammation ,Severity of Illness Index ,Procalcitonin ,Arthritis, Rheumatoid ,Cohort Studies ,0302 clinical medicine ,Immunopathology ,Immunology and Allergy ,skin and connective tissue diseases ,Aged, 80 and over ,0303 health sciences ,General Medicine ,Middle Aged ,Prognosis ,3. Good health ,C-Reactive Protein ,Rheumatoid arthritis ,Acute Disease ,Female ,medicine.symptom ,Inflammation Mediators ,E-Selectin ,musculoskeletal diseases ,Adult ,medicine.medical_specialty ,Adolescent ,Immunology ,Inflammation ,Arthritis, Reactive ,Sensitivity and Specificity ,Statistics, Nonparametric ,Sepsis ,03 medical and health sciences ,Rheumatology ,Internal medicine ,Prohibitins ,medicine ,Humans ,Reactive arthritis ,030304 developmental biology ,Aged ,Probability ,030203 arthritis & rheumatology ,business.industry ,CD11 Antigens ,bacterial infections and mycoses ,medicine.disease ,business ,Biomarkers - Abstract
Objective: To compare systemic inflammation in reactive arthritis (ReA), rheumatoid arthritis (RA), and sepsis using novel markers of systemic inflammation, and to study whether they are helpful in distinguishing between ReA and RA.Methods: In 28 patients with acute ReA, 16 patients with early untreated RA, and 25 patients with blood culture‐positive sepsis, phagocyte CD11b expression was measured by flow cytometry, serum procalcitonin (PCT) levels by immunoluminometric assay, and soluble E‐selectin (sE‐selectin) levels by enzyme‐linked immunosorbent assay (ELISA).Results: Neutrophil and monocyte CD11b expression and serum levels of PCT and sE‐selectin were higher in patients with sepsis than patients with ReA or RA, or in healthy subjects (all p
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- 2004
110. Activation of protein C during reperfusion in clinical liver transplantation
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Heikki Repo, José A. Fernández, Sten-Erik Jansson, Minna Ilmakunnas, Jari Petäjä, Krister Höckerstedt, Eero Pesonen, John H. Griffin, and Heikki Mäkisalo
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Adult ,Male ,medicine.medical_specialty ,Neutrophils ,medicine.medical_treatment ,Inflammation ,Liver transplantation ,Monocytes ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,Hepatic Artery ,Postoperative Complications ,Protein C deficiency ,Internal medicine ,medicine ,Humans ,L-Selectin ,030304 developmental biology ,Aged ,0303 health sciences ,Transplantation ,Phagocytes ,CD11b Antigen ,business.industry ,Monocyte ,Thrombosis ,Middle Aged ,medicine.disease ,Blood proteins ,Liver Transplantation ,Endocrinology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Reperfusion Injury ,Immunology ,Female ,medicine.symptom ,business ,Protein C ,medicine.drug - Abstract
Background Activated protein C (APC) exhibits anticoagulant and antiinflammatory properties. We studied the kinetics and magnitude of protein C activation in clinical liver transplantation and the interaction of this activation with neutrophil and monocyte activation. Methods. In 10 patients undergoing liver transplantation, we measured plasma protein C and APC levels, neutrophil and monocyte CDllb and L-selectin expression, and leukocyte differential counts pre-, intra-, and postoperatively. Samples of blood entering and leaving the liver were obtained simultaneously to assess changes across the liver. Results. Protein C level was low preoperatively (65%, range 39%-141%) and remained low throughout surgery. Compared with the preoperative level (107%, range 78%-161%), APC level increased during liver reperfusion (471%, range 183%-917%, P=0.05). A transhepatic decrease in protein C level (-16%, range -45%-5%, P=0.007), but not in APC level, occurred during initial liver reperfusion. At the same time, neutrophil and monocyte activation took place in the liver. Conclusions. Despite protein C deficiency, patients with liver insufficiency are able to maintain normal APC levels. During reperfusion, protein C consumption occurs in the liver without concomitant hepatic release of APC, indicating a shortage of APC in the reperfused liver. The process consuming protein C and APC may be related to the simultaneous ongoing neutrophil and monocyte activation within the liver graft, indicating a regulatory role for APC in inflammation.
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- 2003
111. Markers of inflammation in sepsis
- Author
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A. Takala, Irmeli Nupponen, Marja-Leena Kylänpää-Bäck, and Heikki Repo
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Adult ,Time Factors ,Secondary infection ,Inflammation ,Shock, Hemorrhagic ,Systemic inflammation ,Proinflammatory cytokine ,Sepsis ,Immune system ,medicine ,Humans ,business.industry ,Organ dysfunction ,Infant, Newborn ,General Medicine ,medicine.disease ,Systemic Inflammatory Response Syndrome ,Pancreatitis ,Immunology ,Acute Disease ,Acute pancreatitis ,Cytokines ,medicine.symptom ,business ,Biomarkers - Abstract
Pathophysiology of sepsis is characterised by a whole body inflammatory reaction and concurrent activation of the host's anti-inflammatory mechanisms. The balance between pro- and anti-inflammatory reactions is critical for the outcome of the patient. Strongly activated phagocytes and high levels of proinflammatory cytokines occur in patients who are at risk of developing circulatory shock and multiple organ dysfunction. Extensive anti-inflammatory reaction, which is characterised by the presence of high levels of circulating anti-inflammatory cytokines and impaired innate and adaptive immune functions, renders critically ill patients prone to secondary infections. Evaluation of the immune-inflammatory status on admission to the hospital may be helpful in the early identification of patients who are bound to develop organ dysfunction. Such patients could possibly benefit from a mode of therapy aimed at modifying the course of inflammatory response. The use of inflammatory markers may also improve diagnosis of severe infection. The present review summarises the studies on markers of inflammation and immune suppression used, first, as predictors of organ dysfunction in patients with systemic inflammation, and, second, as indicators of infection in adults and neonates.
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- 2003
112. CD14 and TNfa promoter polymorphisms in patients with acute arthritis. Special reference to development of chronic spondyloarthropathy
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Heikki, Repo, Krista, Anttonen, Sami K, Kilpinen, Aarno, Palotie, Petri, Salven, Arto, Orpana, and Marjatta, Leirisalo-Repo
- Subjects
Adult ,Male ,Polymorphism, Genetic ,Tumor Necrosis Factor-alpha ,Lipopolysaccharide Receptors ,Middle Aged ,Arthritis, Reactive ,Polymerase Chain Reaction ,Sex Factors ,Acute Disease ,Chronic Disease ,Prohibitins ,Humans ,Spondylarthropathies ,Female ,Genetic Predisposition to Disease ,Age of Onset ,Promoter Regions, Genetic ,Aged ,DNA Primers - Abstract
To examine CD14 and TNFalpha gene polymorphisms in early arthritis in relation to clinical outcome.We studied 141 Caucasians who had had early arthritis 10 to 38 years earlier. We analysed CD14 (-159) and TNFalpha (-238, -308, -376) polymorphisms using a novel cycle minisequencing method. DNA pools from 370 Caucasian blood donors served as controls.CD14 (-159)C--T allele frequencies were comparable among patients and controls (39% vs 40%). Fifty men and 42 women had recovered while 24 men and six women had chronic spondyloarthropathy (SpA). Mutant T allele frequency was higher in the chronic SpA group than in the recovered group in women (75% vs 32%, relative risk 1.3, 95% confidence limit 1.1 to 1.6, P = 0.011), but not in men (38% vs 44%). All female patients with chronic SpA had CD14 (-159)T allele and none had a possibly protective TNFalpha (-308)G--A allele.Possession of CD14 (-159)T allele does not increase risk of ReA but may increase susceptibility of female patients to development of chronic SpA.
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- 2002
113. Early dexamethasone decreases expression of activation markers on neutrophils and monocytes in preterm infants
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Irmeli Nupponen, Heikki Repo, A Kari, Maija Pohjavuori, and Sören Andersson
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Male ,medicine.medical_specialty ,medicine.drug_class ,Neutrophils ,CD14 ,Anti-Inflammatory Agents ,Lipopolysaccharide Receptors ,Dexamethasone ,03 medical and health sciences ,0302 clinical medicine ,Phagocytosis ,030225 pediatrics ,Internal medicine ,medicine ,Humans ,L-Selectin ,Chemokine CCL4 ,030304 developmental biology ,Chemokine CCL3 ,0303 health sciences ,Respiratory Distress Syndrome, Newborn ,CD11b Antigen ,biology ,Respiratory distress ,business.industry ,Monocyte ,Respiratory disease ,Infant, Newborn ,General Medicine ,Macrophage Inflammatory Proteins ,medicine.disease ,Flow Cytometry ,3. Good health ,Endocrinology ,medicine.anatomical_structure ,Bronchopulmonary dysplasia ,Pediatrics, Perinatology and Child Health ,Immunology ,biology.protein ,Leukocytes, Mononuclear ,Corticosteroid ,L-selectin ,Female ,business ,medicine.drug - Abstract
AIM To investigate the effects of early dexamethasone administration on activation of circulating neutrophils and monocytes in preterm infants with respiratory distress syndrome requiring treatment with surfactant. METHODS Neonates (n = 30) with respiratory distress were randomized to receive dexamethasone (DEX group, 29.1 +/- 1.2 wk, 1223 +/- 156 g, n = 15) from the first postnatal day, or to serve as controls (control group, 29.2 +/- 1.4 wk, 1250 +/- 148 g, n = 15). Dexamethasone was given as a 4 d course (0.5 mg kg(-1) on postnatal days 1 and 2, and 0.25 mg kg(-1) on days 3 and 4). Polymorphonuclear leucocyte (PMN) and monocyte surface expression of CD11b, L-selectin and CD14 was quantified with flow cytometry, and plasma macrophage-inflammatory protein-1alpha (MIP-1alpha) with an enzyme-linked immunosorbent assay. Blood samples were collected on days 1, 2-3 and 5-7. RESULTS In the DEX group 1/15, and in the control group 7/15 developed bronchopulmonary dysplasia (p < 0.04). PMN CD11b (median 100, range 70-190 vs 154, 96-213, p=0.01), monocyte CD14 (235, 102-433 vs 355, 219-533, p=0.01) and plasma MIP-1alpha (20 ng l(-1), 20-32 vs 37 ng l(-1), 20-70, p = 0.005) were lower in the DEX group at days 2-3. All adhesion molecule expression and plasma MIP-1alpha levels were comparable at days 5-7, with the exception of monocyte L-selectin expression levels, which remained lower in the DEX group. CONCLUSION In preterm infants with respiratory distress syndrome, early dexamethasone causes downregulation of PMN and monocyte activation. This may attenuate pulmonary inflammation and improve pulmonary outcome.
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- 2002
114. Cellular markers of systemic inflammation and immune suppression in patients with organ failure due to severe acute pancreatitis
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Reijo Haapiainen, Pauli Puolakkainen, Sten-Erik Jansson, Esko Kemppainen, Annika Takala, H. Kautiainen, Marja-Leena Kylänpää-Bäck, and Heikki Repo
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Adult ,Male ,medicine.medical_treatment ,Multiple Organ Failure ,Macrophage-1 Antigen ,Inflammation ,Systemic inflammation ,Monocytes ,Immune system ,Immunopathology ,medicine ,Humans ,Prospective Studies ,Aged ,Aged, 80 and over ,business.industry ,Organ dysfunction ,Gastroenterology ,Immunosuppression ,HLA-DR Antigens ,Middle Aged ,medicine.disease ,Prognosis ,Pancreatitis ,Immunology ,Acute Disease ,Acute pancreatitis ,Female ,medicine.symptom ,business ,Biomarkers - Abstract
Few data are available on cellular markers of systemic inflammation and immune suppression in early acute pancreatitis. The aim of this study was to describe the cellular immune inflammatory status of patients with acute pancreatitis in relation to development of organ failure.Prospective study including 89 patients who presented within 72 h of onset of pain. Fifty-eight of them had mild disease (Grade I group), 19 had severe disease with no organ dysfunction (Grade II group) and 12 had severe disease with organ dysfunction (Grade III group). Serial blood samples were collected on admission and following 2 days. Phagocyte surface markers were analysed using flow cytometry.The proportion of HLA-DR-positive monocytes, a marker of immune suppression, and CD11b expression level on neutrophils and monocytes, a marker of systemic inflammation, were related to Grades I-III (P for trend0.001). In Grade III patients, the proportion of HLA-DR-positive monocytes was low on presentation, or decreased rapidly during follow-up, whereas CD11b expression levels were persistently high. L-selectin and monocyte CD14 expression levels were not related to disease severity.Immune suppression develops early, rapidly and unexpectedly in patients with acute pancreatitis. Monitoring immune inflammatory status may provide the means by which to identify patients who benefit from biological response modifier therapy.
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- 2001
115. Endotoxins induce and interferon alpha suppresses vascular endothelial growth factor (VEGF) production in human peripheral blood mononuclear cells
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Heikki Joensuu, Arto Orpana, Krista Anttonen, Heikki Repo, and Petri Salven
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Salmonella typhimurium ,Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,Angiogenesis ,Ischemia ,Vascular permeability ,Endothelial Growth Factors ,Biology ,Systemic inflammation ,Biochemistry ,Peripheral blood mononuclear cell ,Models, Biological ,Culture Media, Serum-Free ,Aortic aneurysm ,chemistry.chemical_compound ,Internal medicine ,Genetics ,medicine ,Humans ,Molecular Biology ,Lymphokines ,Dose-Response Relationship, Drug ,Vascular Endothelial Growth Factors ,Interferon-alpha ,medicine.disease ,Phenotype ,Vascular endothelial growth factor ,Endotoxins ,Endocrinology ,chemistry ,Cancer research ,Leukocytes, Mononuclear ,medicine.symptom ,Biotechnology - Abstract
SPECIFIC AIMBoth circulating and resident inflammatory cells release diverse factors known to modify vascular permeability, enhance angiogenic phenotypes, and contribute to many vascular events, including atherosclerotic plaque development and rupture, aortic aneurysm formation, ischemia/reperfusion damage and repair, and tumor angiogenesis. The aim of the present study was to explore the role of human peripheral blood mononuclear cells (PBMNCs) as producers of vascular endothelial growth factor (VEGF), and to identify factors that regulate the VEGF biosynthesis and release by PBMNCs.PRINCIPAL FINDINGS1. Unstimulated PBMNCs from healthy donors are able to release VEGF protein continuously into culture mediaFreshly isolated PBMNCs from healthy volunteers cultured for 24 h in serum-free medium in the absence of any stimulus released VEGF continuously into the surrounding medium in a time-dependent manner as determined by ELISA.2. Physiological endotoxin concentrations cause a dose-dependent increase in VEGF...
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- 2001
116. Procalcitonin strip test in the early detection of severe acute pancreatitis
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Pauli Puolakkainen, M L Kylänpää-Bäck, Annika Takala, Reijo Haapiainen, Esko Kemppainen, and Heikki Repo
- Subjects
Adult ,Calcitonin ,Male ,medicine.medical_specialty ,Pancreatic disease ,Calcitonin Gene-Related Peptide ,Apache II score ,030230 surgery ,Systemic inflammation ,Gastroenterology ,Sensitivity and Specificity ,Procalcitonin ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,Humans ,Prospective Studies ,Protein Precursors ,Prospective cohort study ,Aged ,Reagent Strips ,Aged, 80 and over ,Analysis of Variance ,biology ,business.industry ,C-reactive protein ,Length of Stay ,Middle Aged ,medicine.disease ,3. Good health ,Surgery ,Pancreatitis ,Acute Disease ,biology.protein ,Acute pancreatitis ,030211 gastroenterology & hepatology ,Female ,medicine.symptom ,business ,Biomarkers - Abstract
BackgroundEarly identification of patients who subsequently develop severe acute pancreatitis would enable the selection of patients who may benefit from early intensive management. Because severe acute pancreatitis is characterized by the development of systemic inflammation the authors studied whether procalcitonin, a marker of systemic inflammation, differentiated between patients with mild and severe acute pancreatitis.MethodsOn admission and 24 h thereafter, serum procalcitonin level was measured by a rapid, semiquantitative PCT®-Q test and serum C-reactive protein (CRP) by an immunoturbidimetric method in a consecutive series of 162 patients with acute pancreatitis. There were 38 severe and 124 mild cases. The accuracy of procalcitonin and CRP in predicting severe acute pancreatitis was compared with that of Ranson and Acute Physiology and Chronic Health Evaluation (APACHE) II scores.ResultsThe PCT®-Q test was more accurate in predicting severe acute pancreatitis (sensitivity 92 per cent and specificity 84 per cent at 24 h) than CRP, APACHE II score and Ranson score. Its negative predictive value was high (97 per cent at 24 h), and it detected each patient who developed subsequent organ failure (n = 22).ConclusionThe PCT®-Q test was a useful screening method for detecting severe acute pancreatitis. It is simple and quick to perform and, unlike currently available multiple factor scoring systems, can easily be adopted into routine clinical practice.
- Published
- 2001
117. Subejct Index Vol. 96, 2009
- Author
-
Janet Stone, Sture Andersson, Yasushi Ohki, Marianne Thoresen, Pattie Bondurant, Masayuki Watanabe, Eero Kajantie, Maureen Rider, Yukihiro Yoshizawa, Irmeli Nupponen, Christine A. Gleason, Mark H. Oliver, Ronald J. McPherson, Thuy N. Vien, Sarah L. Hays, Tamina White, Mauricio Odio, Sandra E. Juul, Carl A Kuschel, Diane Goltz, Aulikki Lano, Sanna Siitonen, Ulrike Herberg, Katinka P. Bach, Teresa Flower, Johannes Breuer, Frank H. Bloomfield, Linda Sluder, Kenichi Tokuyama, Beth Mason, Louise Smith, Ulrich Gembruch, Mathias Karlsson, Outi Vaarala, Saulius Satas, Marty O. Visscher, Shelly Sargent, Akihiro Morikawa, Teresa Taylor, Riikka Turunen, Yukiko Takahashi, Charles Chavkin, Hiroo Mayuzumi, Michael Obladen, Amy Huebner, Heikki Repo, Helen Porter, and Henning Weiss
- Subjects
Pediatrics, Perinatology and Child Health ,Developmental Biology - Published
- 2009
118. Markers of systemic inflammation predicting organ failure in community-acquired septic shock
- Author
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ANNIKA TAKALA, Irma Jousela, Jan-Erik Jansson, Klaus Olkkola, Olli Takkunen, Arto Orpana, Sirkka-Liisa Karonen, and Heikki Repo
- Subjects
Adult ,Aged, 80 and over ,Male ,Adolescent ,Interleukin-6 ,Multiple Organ Failure ,Interleukin-8 ,Macrophage-1 Antigen ,Receptors, Interleukin-2 ,General Medicine ,Middle Aged ,Shock, Septic ,Blood Cell Count ,Community-Acquired Infections ,C-Reactive Protein ,Humans ,Female ,E-Selectin ,Biomarkers ,APACHE ,Aged - Abstract
To obtain predictors of organ failure (OF), we studied markers of systemic inflammation [circulating levels of interleukin-6 (IL-6), IL-8, soluble IL-2 receptor (sIL-2R), soluble E-selectin and C-reactive protein, and neutrophil and monocyte CD11b expression] and routine blood cell counts in 20 patients with systemic inflammatory response syndrome and positive blood culture. Eight patients with shock due to community-acquired infection developed OF, whereas 11 normotensive patients and one patient with shock did not (NOF group). The first blood sample was collected within 48 h after taking the blood culture (T1). OF patients, as compared with NOF patients, had at T1 a lower monocyte count, a lower platelet count, higher levels of CD11b expression on both neutrophils and monocytes, and higher concentrations of IL-6, IL-8 and sIL-2R. C-reactive protein and soluble E-selectin concentrations did not differ between groups. No parameter alone identified all patients that subsequently developed OF. However, a sepsis-related inflammation severity score (SISS), developed on the basis of the presence or absence of shock and on the levels of markers at T1, identified each patient that developed OF. The maximum SISS value was 7. The range of SISS values in OF patients was 2-5, and that in NOF patients was 0-1. In conclusion, high levels of CD11b expression, depressed platelet and monocyte counts, and high concentrations of IL-6, IL-8 and sIL-2R predict OF in patients with community-acquired septic shock, and the combination of these markers may provide the means to identify sepsis patients who will develop OF.
- Published
- 1999
119. Mechanisms and consequences of phagocyte adhesion to endothelium
- Author
-
Heikki Repo and John M. Harlan
- Subjects
Integrins ,Endothelium ,Integrin ,Leukocyte-Adhesion Deficiency Syndrome ,Immunoglobulins ,Inflammation ,03 medical and health sciences ,0302 clinical medicine ,Platelet Adhesiveness ,Cell Adhesion ,Medicine ,Humans ,Cell adhesion ,030304 developmental biology ,0303 health sciences ,Phagocytes ,biology ,business.industry ,Cell adhesion molecule ,Soluble cell adhesion molecules ,General Medicine ,Adhesion ,Systemic Inflammatory Response Syndrome ,3. Good health ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Selectins ,medicine.symptom ,business ,Cell Adhesion Molecules ,Selectin ,Biomarkers - Abstract
Leukocyte adhesion to endothelium is essential for the development of an appropriate immune-inflammatory response. The vital importance of leukocyte-endothelial adhesive interactions in host defense and homeostasis is illustrated by the clinical manifestations of patients with congenital defects of leukocyte adhesion functions. However, under some circumstances leukocyte adhesion to endothelium may instead lead to vascular and tissue damage. In recent years, there has been remarkable progress in the understanding of the molecular basis of leukocyte adhesion to endothelium, and this knowledge has led to a new approach to immunomodulation in human disease, ie 'antiadhesion' therapy. This review focuses on cell adhesion molecules mediating adhesion of circulating phagocytes to vascular endothelium, on congenital defects of phagocyte adhesion in man, and on the current status of antiadhesion therapy directed towards phagocyte and endothelial adhesion molecules. We will also consider markers of phagocyte activation, which may provide a means to identify those patients who would benefit most from antiadhesion therapy.
- Published
- 1999
120. HAEMOSTATIC GENE POLYMORPHISM IN SEVERE ACUTE PANCREATITIS
- Author
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Heikki Repo, Reijo Haapiainen, Esko Kemppainen, Eija Tukiainen, Marja-Leena Kylänpää, Pauli Puolakkainen, Arto Orpana, Taina Methuen, and Mikko Salaspuro
- Subjects
medicine.medical_specialty ,Endocrinology ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Internal medicine ,Internal Medicine ,medicine ,Acute pancreatitis ,Gene polymorphism ,business ,medicine.disease ,Gastroenterology - Published
- 2008
121. Preface
- Author
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Marjatta Leirisalo-Repo and Heikki Repo
- Subjects
Rheumatology - Published
- 2006
122. SAT0479 Bloodstream Infections (BSI) in Finnish Children with Juvenile Idiopathic Arthritis in 2004-2011
- Author
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Säilä H, J. H. Salonen, Hannu Kautiainen, P. H. Salonen, Markku J Kauppi, M. Vuorela, O. Lyytikainen, Marjatta Leirisalo-Repo, and Heikki Repo
- Subjects
Pediatrics ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Immunology ,Arthritis ,Disease ,medicine.disease_cause ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Pneumonia ,Standardized mortality ratio ,Rheumatology ,Staphylococcus aureus ,Streptococcus pneumoniae ,medicine ,Immunology and Allergy ,Infectious disease (athletes) ,business - Abstract
Background The treatment of JIA has become more effective by means of biological disease modifying antirheumatic drugs (DMARDs). Biological DMARDs, however, increase the risk of infections. Objectives The aim of the study is to find out the incidence and the individual risk factors for bloodstream infections in JIA. Methods The Social Insurance Institution (SII) register of reimbursement of medicines and National Infectious Disease Register (National Institute of Health and Welfare) were used to identify JIA patients aged 2-18 years hospitalized for BSI during the years 2004-2011. Antirheumatic treatment of JIA was searched by using SII nationwide register. We also analysed the incidence of BSI in JIA patients with new diagnosis during the study period, and compared it with BSI in Finnish population of same age and study period. Results By means of combination of the register data we found a total of 10 patients (11 episodes) with BSI during the study period. The median age of children was 14 years. One patient had two distinct episodes of BSI. Pneumonia was the most common focus of infection. The following bacteria were detected: Staphylococcus aureus (4 cases), Streptococcus pneumoniae (3 cases), Staphylococcus epidermidis, Escherichia coli, Fusobacterium necroforum and Pseudomonas aeruginosa in one patient, respectively. Six patients were on biological DMARD and four on glucocorticoid treatment. We identified 1604 patients with JIA diagnosed in 2004-2011 with 6630 patient years of follow-up. Five JIA patients (7.5 infections/10 000 patient years, 95% CI 2.4 – 17.6) and 2184 control population subjects (2.8 infections/ 10 000 patient years, 95% CI 2.7 – 2.9) had BSI. Conclusions Bloodstream infections seem to be rare in patients with JIA. Interestingly, half of the patients with BSI were on biological DMARDs. Compared with control population, the standardized incidence ratio for BSI in JIA patients was 3.0 (95% CI 1.25 – 7.20). References Hashkes PJ, Uziel Y, Laxer RM. The safety profile of biologic therapies for juvenile idiopathic arthritis. Nat Rev Rheumatol 2010;6:561-571. Beukelman T, Xie F, Chen L et al. Rates of hospitalized bacterial infection associated with juvenile idiopathic arthritis and its treatment. Arthritis Rheum 2012;64:2773-2780. Disclosure of Interest None Declared
- Published
- 2013
123. Anti-inflammatory macrophage induced MMP9 and ADAM8 expression increases invasion rate of pancreatic cancer cells
- Author
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Heikki Repo, Harri Mustonen, Pauli Puolakkainen, Z.H. Shen, Sanna Vainionpää, Hanna Seppänen, and Esko Kemppainen
- Subjects
Hepatology ,medicine.drug_class ,business.industry ,Endocrinology, Diabetes and Metabolism ,Gastroenterology ,MMP9 ,medicine.disease ,Anti-inflammatory ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Pancreatic cancer ,Cancer research ,medicine ,Macrophage ,030211 gastroenterology & hepatology ,business ,ADAM8 - Published
- 2013
124. Cytokines as predictors of organ failure in severe acute pancreatitis
- Author
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Mikael Maksimow, Anne Nieminen, Pauli Puolakkainen, Panu Mentula, Lea Kyhälä, Heikki Repo, Esko Kemppainen, Marko Salmi, and Leena Kylänpää
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Gastroenterology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,medicine ,Acute pancreatitis ,030211 gastroenterology & hepatology ,Intensive care medicine ,business - Published
- 2013
125. Time course of beta 2-integrin CD11b/CD18 (Mac-1, alpha M beta 2) upregulation on neutrophils and monocytes after coronary artery bypass grafting. CD11b upregulation after CABG surgery
- Author
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Klaus T. Olkkola, Heikki Repo, Kimmo Kyösola, O. Takkunen, Sten-Erik R. Jansson, A. Takala, Irma Jousela, and Marjatta Leirisalo-Repo
- Subjects
Male ,medicine.medical_specialty ,Neutrophils ,medicine.medical_treatment ,Macrophage-1 Antigen ,CD18 ,030204 cardiovascular system & hematology ,Monocytes ,Neutrophil Activation ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,law ,Internal medicine ,medicine ,Cardiopulmonary bypass ,Humans ,Coronary Artery Bypass ,Vein ,030304 developmental biology ,0303 health sciences ,biology ,business.industry ,Monocyte ,3. Good health ,Up-Regulation ,medicine.anatomical_structure ,Integrin alpha M ,CD18 Antigens ,biology.protein ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Central venous catheter ,Artery - Abstract
Although upregulation of CD11b/CD18 receptor, i.e. activation of neutrophils and monocytes, during cardiopulmonary bypass is well documented, the duration of the active state after uncomplicated operation is less understood. We therefore investigated CD11b expression of phagocytes in blood samples collected 2-4, 24, 48 and 72 h after coronary artery bypass grafting. CD11b expression on neutrophils was significantly elevated at 2-4 and 24 hours after operation as compared with baseline. On monocytes, expression peaked at 24 h and returned to baseline by 72 h. Because CD11b is a sensitive marker, effects of different sampling techniques on its expression were also studied. CD11b expression was similar in samples collected with a syringe from arterial or central venous catheter or with open technique from cubital vein. On neutrophils from healthy subjects, sampling with syringe caused small (10%) but statistically significant increase of expression. We conclude that activated neutrophils disappear from circulation within hours after CABG surgery while activated monocytes may continue circulating for 2-3 days, and that CD11b sampling can be done with a syringe.
- Published
- 1996
126. THE EFFECT OF ALBUMIN DIALYSIS ON CYTOKINE LEVELS IN ACUTE LIVER FAILURE AND NEED FOR LIVER TRANSPLANTATION
- Author
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H. Isoniemi, Heikki Repo, Antti Koivusalo, and K r Höckerstedt
- Subjects
Transplantation ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Albumin ,Bioartificial liver device ,Liver failure ,Liver transplantation ,Gastroenterology ,law.invention ,Cytokine ,law ,Internal medicine ,medicine ,Liver function tests ,business ,Dialysis - Published
- 2004
127. Serum Levels of Mast Cell Tryptase, Vascular Endothelial Growth Factor, and Basic Fibroblast Growth Factor in Patients With Acute Pancreatitis: Reply
- Author
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Panu Mentula, Marja-Leena Kyl??np????, and Heikki Repo
- Subjects
Endocrinology ,Hepatology ,Endocrinology, Diabetes and Metabolism ,Internal Medicine - Published
- 2004
128. Anticoagulant selection influences flow cytometric determination of CD11b upregulation in vivo and ex vivo
- Author
-
Heikki Repo, Sten-Erik Jansson, and Marjatta Leirisalo-Repo
- Subjects
Adult ,Male ,Cell Survival ,Neutrophils ,Immunology ,Macrophage-1 Antigen ,Buffy coat ,Monocytes ,Neutrophil Activation ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,medicine ,Immunology and Allergy ,Humans ,Cell damage ,030304 developmental biology ,Whole blood ,0303 health sciences ,biology ,Chemistry ,Monocyte ,Temperature ,Anticoagulants ,medicine.disease ,Flow Cytometry ,Up-Regulation ,N-Formylmethionine Leucyl-Phenylalanine ,medicine.anatomical_structure ,Biochemistry ,13. Climate action ,030220 oncology & carcinogenesis ,biology.protein ,Female ,Antibody ,Cell activation ,Ex vivo - Abstract
We recently devised three-colour flow cytometric assay for evaluating expression of CD11b on neutrophils and monocytes in circulation. Artefactual upregulation of CD11b ex vivo was minimized by cooling blood samples on ice. In this communication we further characterize the method in terms of different anticoagulants. EDTA was less optimal than ACD or heparin because (i) saturating concentrations of CD11b antibody (clone D12) were not achieved with resting cells; (ii) CD11b fluorescence intensity of synovial fluid cells, i.e., in vivo activated cells expressing CD11b at high levels, was significantly lower in EDTA plasma, and (iii) EDTA mediated more cell damage at 37 degrees C, as determined by PI staining. The fluorescence data suggested that D12 antibody binding was dependent on divalent cations. Saturating concentrations in the presence of EDTA in medium were easily obtained with synovial fluid cells and peripheral blood phagocytes activated with chemotactic peptide FMLP, suggesting that cell activation decreased cation concentrations required for D12 antibody binding. Using another CD11b antibody (2MPL19c), whose binding proved to be cation independent, it was shown that CD11b upregulation was not affected by EDTA. ACD was superior to heparin and phenylalanylprolylarginyl chloromethyl ketone (PPACK), a thrombin inhibitor, because cell counts were significantly lower in heparinized samples in cold, and in PPACK-anticoagulated samples treated with LPS at 37 degrees C. Kinetics of L-selectin shedding was similar in heparin and ACD, suggesting that cell loss did not derive from differences in cell activation. In comparison of buffy coat cell assay and whole blood assay, neutrophil CD11b expression was similar but background fluorescence was significantly higher in whole blood preparations. This implies that nonspecific antibody binding may occur more in whole blood assay, whereas in the buffy coat cell assay, sample manipulation procedures may slightly increase CD11b antibody binding, but not control antibody binding. Finally, it was confirmed that warming from 0 degrees C, but not from room temperature, to 37 degrees C increased CD11b expression significantly on neutrophils, and it was further shown that monocytes undergo similar changes. Cooling did not upregulate CD11b, and completely prevented LPS-induced upregulation. In conclusion, the results support use of ACD in evaluating CD11b expression; if EDTA is used, it is important to make sure that binding of CD11b antibody selected does not require presence of divalent cations in medium.
- Published
- 1995
129. Inhaled recombinant interferon gamma in patients with lung cancer: pharmacokinetics and effects on chemiluminescence responses of alveolar macrophages and peripheral blood neutrophils and monocytes
- Author
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Heikki Repo, Paula Maasilta, Karin Mattson, Matti Ristola, Kari Cantell, Maija Halme, and Eero Taskinen
- Subjects
Adult ,Male ,Cancer Research ,Lung Neoplasms ,Time Factors ,Neutrophils ,Monocytes ,03 medical and health sciences ,chemistry.chemical_compound ,Interferon-gamma ,0302 clinical medicine ,Pharmacokinetics ,Carcinoma, Non-Small-Cell Lung ,Macrophages, Alveolar ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Interferon gamma ,Carcinoma, Small Cell ,030304 developmental biology ,Aged ,Respiratory Burst ,Aerosols ,0303 health sciences ,Radiation ,medicine.diagnostic_test ,Inhalation ,business.industry ,Zymosan ,Macrophage Activation ,Middle Aged ,Recombinant Proteins ,3. Good health ,Respiratory burst ,medicine.anatomical_structure ,Bronchoalveolar lavage ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Immunology ,Luminescent Measurements ,Female ,Pulmonary alveolus ,business ,Reactive Oxygen Species ,Bronchoalveolar Lavage Fluid ,Respiratory tract ,medicine.drug - Abstract
Purpose: A phase I trial was conducted to investigate clinical toxicity, pharmacokinetics, and chemiluminescence (CL) response of alveolar machrophage (AM) and peripheral blood neutrophils and monocytes after inhalation of recombinant interferon (r IFN)-gamma. Methods and Materials: Eight patients with lung cancer inhaled r IFN-gamma as single doses of 0.1, 0.2, 0.6, 1.8, or 5.4 mg. Bronchoalveolar lavage was performed three times, 21 h before as well as 3 and 27 h after inhalation. Results: Interferon-gamma was detectable in bronchoalveolar lavage fluid (BALF) samples taken 3 h after inhalation in doses of ≥ 0.6 mg. Before inhation, AM in four out of seven patients studied showed vigorous lucigenin-enhanced CL responses to N -formyl-methionyl-leucyk-phenylalanine and opsonized zymosan particles. Futhermore, the responses were markedly increase 3 h after inhalation. In three out of seven patients, AM in the pretreatment BALF samples showed low or no CL responses, and the responses did not increase after inhalation of IFN-gamma, suggesting that the patients were anergic. Postinhalation CL responses did not correlate with the dose of IFN-gamma inhaled. Circulating IFN-gamma was detected in one patient receiving the highest dose. No changes referable to IFN-gamma inhalation were found in the CL responses to blood neutrophils and monocytes. During the 24 h follow-up, two patients developed transient fever-reactions. Conclusions: The findings suggest that inhalation may provide a way to increase alveolar concentrations of IFN-gamma and to augment respiratory burst capacity of AM without any major side effects. This approach may have clinical implications for the treatment of tumors and infections of the respiratory tract.
- Published
- 1995
130. Production of TNF by monocytes of patients with early rheumatoid arthritis is increased
- Author
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Saija Koskimies, Marjatta Leirisalo-Repo, Leena Paimela, M. Jäätteä, and Heikki Repo
- Subjects
Adult ,Lipopolysaccharides ,Male ,medicine.medical_specialty ,Time Factors ,Lipopolysaccharide ,medicine.medical_treatment ,Immunology ,Inflammation ,Severity of Illness Index ,Monocytes ,Arthritis, Rheumatoid ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Rheumatology ,Immunopathology ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,Cells, Cultured ,030304 developmental biology ,030203 arthritis & rheumatology ,Autoimmune disease ,0303 health sciences ,business.industry ,Tumor Necrosis Factor-alpha ,Monocyte ,General Medicine ,Middle Aged ,medicine.disease ,3. Good health ,Culture Media ,Endocrinology ,medicine.anatomical_structure ,Cytokine ,chemistry ,Rheumatoid arthritis ,Antirheumatic Agents ,Tumor necrosis factor alpha ,Female ,medicine.symptom ,business - Abstract
We studied the production of tumour necrosis factor alpha (TNF) by monocytes of patients with early rheumatoid arthritis (RA) before starting disease modifying anti-rheumatic drug treatment and a median 6 months (range 5-11 months) later, and correlated the pre-treatment results with 3-year prognosis. Monocytes of patients (n = 14) and controls (n = 14), isolated by the density gradient centrifugations, were cultured for 24 h with Escherichia coli lipopolysaccharide (LPS) 0-10 micrograms/ml. Before treatment, levels of TNF were higher in LPS-stimulated RA monocyte cultures than in the control cultures; differences were statistically significant in LPS 10 and 0.01 micrograms/ml. At 6 months, respective differences were not significant. Levels of TNF before treatment did not correlate to clinical or laboratory parameters of inflammation, or development of erosions. The results indicate that monocytes of patients with early RA are primed, and that the state of priming decreases during treatment.
- Published
- 1995
131. Acute pancreatitis with organ dysfunction associates with abnormal blood lymphocyte signaling: controlled laboratory study
- Author
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Marja-Leena Kylänpää, Lea Kyhälä, Esko Kemppainen, Sanna Siitonen, Pauli Puolakkainen, Harri Mustonen, Krista Kuuliala, Jani Oiva, and Heikki Repo
- Subjects
Male ,Lymphocyte ,CD3 ,Multiple Organ Failure ,Inflammation ,Systemic inflammation ,Critical Care and Intensive Care Medicine ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,030304 developmental biology ,0303 health sciences ,biology ,business.industry ,Research ,Organ dysfunction ,Lymphocyte differentiation ,medicine.disease ,Lymphocyte Subsets ,3. Good health ,medicine.anatomical_structure ,Pancreatitis ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Acute pancreatitis ,Tumor necrosis factor alpha ,Female ,medicine.symptom ,business ,Signal Transduction - Abstract
Introduction Severe acute pancreatitis is associated with systemic inflammation, compensatory immune suppression, secondary infections, vital organ dysfunction, and death. Our study purpose was to delineate signaling profiles of circulating lymphocytes in acute pancreatitis complicated by organ dysfunction. Methods Sixteen patients with acute pancreatitis, dysfunction of vital organ(s), and immune suppression (proportion of HLA-DR Human Leukocyte Antigen - DR - positive monocytes < 80%) participated. Healthy volunteers served as reference subjects. Using phospho-specific whole blood flow cytometry we studied lymphocyte phosphorylation of nuclear factor-κB (NFκB), mitogen-activated protein kinases p38 and extracellular signal-regulated kinases (ERK)1/2, and signal transducers and activators of transcription (STATs) 1, 3, and 6. Statistical comparisons were performed with the Wilcoxon-Mann-Whitney test. Results In blood samples supplemented with tumor necrosis factor, E. coli or S. aureus, phosphorylation levels of NFκB were lower and levels of p38 were higher in patients with acute pancreatitis than healthy subjects. Low NFκB activation involved CD3+CD4+ and CD3+CD8+ lymphocytes. ERK1/2 phosphorylation induced by co-stimulation with phorbol 12-myristate 13-acetate and calcium ionophore A23187 was depressed in patients. STAT3 was constitutively activated in patients' CD3+CD4+ and CD3+CD8+ lymphocytes. Also, IL-6-induced STAT1 phosphorylation was impaired while IL-4-induced STAT6 phosphorylation was enhanced. Conclusions Lymphocytes of patients with acute pancreatitis, organ dysfunction and immune suppression show impaired NFκB activation, which increases infection risk and enhanced p38 activation, which sustains inflammation. Secondly, they indicate constitutive STAT3 activation, which may favor Th17 lineage of CD4+ lymphocyte differentiation. Thirdly, they reveal impaired STAT1 activation and enhanced STAT6 activation, denoting a shift from Th1 towards Th2 differentiation.
- Published
- 2010
132. Determination of oxygen radical production in spondyloarthropathies by whole blood chemiluminescence
- Author
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Marjatta Leirisalo-Repo, Matti Ristola, and Heikki Repo
- Subjects
Adult ,Male ,medicine.medical_specialty ,Yersinia Infections ,Free Radicals ,Radical ,Immunology ,Arthritis ,Yersinia ,General Biochemistry, Genetics and Molecular Biology ,Luminol ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Rheumatology ,law ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,Spondylitis, Ankylosing ,HLA-B27 Antigen ,030304 developmental biology ,Whole blood ,Chemiluminescence ,Aged ,030203 arthritis & rheumatology ,0303 health sciences ,Ankylosing spondylitis ,Arthritis, Infectious ,biology ,business.industry ,Middle Aged ,biology.organism_classification ,medicine.disease ,3. Good health ,N-Formylmethionine Leucyl-Phenylalanine ,Oxygen ,Endocrinology ,chemistry ,Luminescent Measurements ,Acridines ,Female ,business ,Research Article - Abstract
Oxygen derived free radicals are considered to play an important part in the development of inflammation. A whole blood chemiluminescence assay was used to study N-formyl-methionyl-leucyl-phenylalanine induced oxygen radical production in subjects with ankylosing spondylitis or previous yersinia arthritis. In luminol enhanced chemiluminescence, the subjects with previous yersinia arthritis showed significantly increased initial activation (at one minute), whereas the subjects with ankylosing spondylitis showed decreased responses at both the initial activation and at peak activation (at two to three minutes). This finding gives credence to the view that, in terms of oxygen radical production, the pathogenesis of yersinia arthritis is different from that of ankylosing spondylitis.
- Published
- 1991
133. Increased whole blood chemiluminescence in patients with Shwachman syndrome: therapy trial with thiamine and alpha-tocopherol
- Author
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Emma M. Savilahti, Marjatta Leirisalo-Repo, Matti Ristola, and Heikki Repo
- Subjects
medicine.medical_specialty ,Neutropenia ,Cystic Fibrosis ,Neutrophils ,Neutrophile ,Radical ,alpha-Tocopherol ,Tocopherols ,Antioxidants ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,030225 pediatrics ,Internal medicine ,medicine ,Extracellular ,Humans ,Vitamin E ,Tocopherol ,Thiamine ,030304 developmental biology ,Whole blood ,Chemiluminescence ,0303 health sciences ,business.industry ,Infant, Newborn ,Chemotaxis ,Syndrome ,3. Good health ,Chemotaxis, Leukocyte ,Endocrinology ,Pediatrics, Perinatology and Child Health ,Immunology ,Luminescent Measurements ,Drug Therapy, Combination ,Exocrine Pancreatic Insufficiency ,business - Abstract
Neutrophils purified from peripheral blood of patients with the Shwachman syndrome show enhanced chemiluminescence (CL) and depressed chemotaxis. Here we present data showing that the increased CL response can be demonstrated by using a whole blood CL assay. This assay is well-suited for studies in infants, because the blood sample volumes needed are small. Increase in CL was most distinct in the initial (1 min) activation induced by N-formyl-methionyl-leucyl-phenylalanine. The 1-min response is considered to derive from extracellular production of oxygen radicals. Such an extracellular oxygen radical production may render the patients susceptible to undue oxidant stress. We therefore treated the patients with two antioxidants, thiamine and alpha-tocopherol, for 3 months. This supplementation, however, failed to exert any significant effect on either whole blood CL or migration of the patients' neutrophils under agarose.
- Published
- 1991
134. Phagocyte function in familial hypercholesterolaemia: peripheral blood monocytes exposed to lipopolysaccharide show increased tumour necrosis factor production
- Author
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T. A. Miettinen, Marja Jäättelä, Heikki Repo, Marjatta Leirisalo-Repo, and H Gylling
- Subjects
Adult ,Lipopolysaccharides ,Male ,medicine.medical_specialty ,Phagocyte ,Lipopolysaccharide ,Neutrophils ,medicine.medical_treatment ,Immunology ,Chemokinesis ,Biology ,In Vitro Techniques ,Monocytes ,Hyperlipoproteinemia Type II ,chemistry.chemical_compound ,Cell Movement ,Internal medicine ,medicine ,Humans ,Phagocytes ,Tumor Necrosis Factor-alpha ,Monocyte ,Zymosan ,General Medicine ,Middle Aged ,medicine.anatomical_structure ,Endocrinology ,Cytokine ,chemistry ,Tumor necrosis factor alpha ,Female ,Lipoprotein - Abstract
We studied functions of polymorphonuclear leucocytes (PMN) and monocytes from peripheral blood of subjects with familial hypercholesterolaemia (FH). FH monocytes exposed to Escherichia coli lipopolysaccharide (LPS) in 10% human AB serum generated tumour necrosis factor (TNF) significantly more than did control monocytes. After lowering of serum low-density lipoprotein (LDL) levels by drug treatment, FH monocytes exposed to LPS in the absence of exogenous lipoproteins generated significantly more TNF than did control monocytes. These findings suggest that increased TNF production is not affected by hypolipidaemic treatment and may not derive from differences between uptake of exogenous LDL by FH monocytes and control cells. Chemotaxis, chemokinesis, and random migration of both FH PMN and FH monocytes were normal, as determined by agarose assay and membrane filter assay. FH PMN showed increased luminol-enhanced chemiluminescence in response to 2.5 x 10(-8) M, but not to 2.5 x 10(-6) M, N-formyl-methionyl-leucyl-phenylalanine, and not to serum-treated zymosan or to phorbol myristate acetate. Luminol- and lucigenin-enhanced chemiluminescence responses of FH monocytes were normal. In summary, the major aberration found in the present study was that FH monocytes stimulated with LPS show enhanced production of TNF. The possibility that exaggerated TNF production contributes to an early development of atherosclerotic lesions in FH subjects warrants further studies.
- Published
- 1990
135. A Novel Modification of a Flow Cytometric Assay of Phosphorylated STAT1 in Whole Blood Monocytes for Immunomonitoring of Patients on IFNα Regimen
- Author
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J Vakkila, Ulla Turunen, Pauli Puolakkainen, Leena Halme, H. Nuutinen, Sanna Siitonen, Harri Mustonen, Martti Färkkilä, Heikki Repo, and Urpo Nieminen
- Subjects
Adult ,Male ,CD14 ,Immunology ,Alpha interferon ,Biology ,Monocytes ,Flow cytometry ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Monitoring, Immunologic ,Interferon ,In vivo ,medicine ,Animals ,Humans ,Phosphorylation ,030304 developmental biology ,Whole blood ,0303 health sciences ,medicine.diagnostic_test ,Interferon-alpha ,General Medicine ,Middle Aged ,Flow Cytometry ,Hepatitis C ,In vitro ,3. Good health ,STAT1 Transcription Factor ,030220 oncology & carcinogenesis ,Female ,medicine.drug - Abstract
We explored whether episodes stimulating leucocytes in vivo could be tracked from whole blood samples by monitoring activation of STAT1 by flow cytometry. The method was tested in hepatitis C patients (n = 9) that were on interferon (IFN)alpha regimen. CD14+ monocytes responded strongly to IFNalpha/gamma being sensitive indicators for recent immune activation. At 45 min after s.c. IFNalpha 91% of monocytes were phosphorylated STAT1+. The frequency of responding cells decreased to a base level within 6 h. Monocytes, however, had a long-term deficient phosphorylated STAT1 response to IFNalphain vitro that in patients on standard IFNalpha regimen lasted for 48 h. In patients on pegylated IFNalpha the phosphorylated STAT1 response was completely absent. We conclude that whole blood analysis of STAT1 activation by flow cytometry is applicable to monitor immune cells in patient material.
- Published
- 2007
136. KYNURENINE CATABOLITES OF TRYPTOPHAN CARRIED IN MESENTERIC LYMPH CONTRIBUTE TO PANCREATITIS-ASSOCIATED ORGAN FAILURE IN RATS AND HUMANS
- Author
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Heikki Repo, Damian J. Mole, Edwin A. Deitch, G. Collett, C. O'neill, O. J. Garden, Leena Kylänpää, T Diamond, and Neil V. McFerran
- Subjects
Pathology ,medicine.medical_specialty ,Hepatology ,Endocrinology, Diabetes and Metabolism ,Tryptophan ,Biology ,medicine.disease ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Immunology ,Internal Medicine ,medicine ,Pancreatitis ,Lymph ,Kynurenine - Published
- 2007
137. Cytokine Profiles in Acute Liver Failure Treated With Albumin Dialysis
- Author
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Ilkka Ilonen, Helena Isoniemi, Heikki Repo, Anna-Maria Koivusalo, and Krister Höckerstedt
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Biomedical Engineering ,Medicine (miscellaneous) ,Bioengineering ,Liver transplantation ,Systemic inflammation ,Gastroenterology ,Biomaterials ,Pathogenesis ,Necrosis ,03 medical and health sciences ,0302 clinical medicine ,Albumins ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Interleukin 6 ,Prospective cohort study ,Dialysis ,Aged ,Aged, 80 and over ,biology ,business.industry ,General Medicine ,Liver Failure, Acute ,Middle Aged ,3. Good health ,Interleukin 10 ,Treatment Outcome ,Cytokine ,Liver ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Cytokines ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,Follow-Up Studies - Abstract
Cytokines are released within the liver in response to hepatic injury, and acute liver failure (ALF) triggers systemic inflammation. Pro-inflammatory (tumor necrosis factor-alpha [TNF-alpha] and interleukin-8 [IL-8]) and anti-inflammatory (interleukin-10 [IL-10] and interleukin-6 [IL-6]) cytokines and the lymphocyte activation marker (interleukin-2-soluble receptor alpha chain [IL-2sRalpha]) were monitored in 49 ALF patients considered for liver transplantation and treated with albumin dialysis (molecular adsorbent recirculating system [MARS]). Twenty-six patients were categorized by clinical outcome as "good" (native liver recovered) and 23 as "poor" (patient bridged to liver transplantation or deceased). MARS did not clearly affect cytokine profiles during treatment; only IL-10 levels decreased in the whole patient population and mostly in patients with the worst prognosis. In the good outcome group, IL-8 and IL-6 levels decreased during treatment; on the contrary, in poor outcome patients IL-6 levels even increased. Initial IL-2sRalpha levels were higher in poor outcome patients relative to the good outcome subset. Cytokine profiles seem to differ in ALF according to patient outcome. A deeper understanding of cytokine patterns during pathogenesis could reveal prognostic markers and aid the development of immunomodulating ALF therapies.
- Published
- 2007
138. [Untitled]
- Author
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Jari Petäjä, Heikki Repo, Panu Mentula, Outi Lindström, Leena Kylänpää, John H. Griffin, Esko Kemppainen, Pauli Puolakkainen, José A. Fernández, and Reijo Haapiainen
- Subjects
medicine.medical_specialty ,medicine.drug_class ,Critical Care and Intensive Care Medicine ,Gastroenterology ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Platelet ,Intensive care medicine ,medicine.diagnostic_test ,business.industry ,Monocyte ,Anticoagulant ,medicine.disease ,3. Good health ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Pancreatitis ,Acute pancreatitis ,030211 gastroenterology & hepatology ,business ,Protein C ,Homeostasis ,medicine.drug - Abstract
Disturbed protein C (PC) pathway homeostasis might contribute to the development of multiple organ failure (MOF) in acute pancreatitis (AP). We therefore evaluated circulating levels of PC and activated protein C (APC), evaluated monocyte deactivation in AP patients, and determined the relationship of these parameters to MOF. Thirty-one patients in the intensive care unit were categorized as cases (n = 13, severe AP with MOF) or controls (n = 18, severe AP without MOF). Blood samples were drawn every second day to determine the platelet count, the levels of APC, PC, and D-dimer, and the monocyte HLA-DR expression using flow cytometry. The APC/PC ratio was used to evaluate turnover of PC to APC. During the initial two weeks of hospitalization, low PC levels (
- Published
- 2006
139. TNF-??, HSP70-2 AND CD14 POLYMORPHISMS IN ACUTE PANCREATITIS
- Author
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Heikki Repo, Pauli Puolakkainen, M L Kyl np, Reijo Haapiainen, Eija Tukiainen, Kimmo I. Halonen, Esko Kemppainen, Taina Methuen, and Mikko Salaspuro
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,CD14 ,medicine.disease ,Gastroenterology ,Hsp70 ,Endocrinology ,Internal medicine ,Internal Medicine ,medicine ,Acute pancreatitis ,Tumor necrosis factor alpha ,business - Published
- 2005
140. UP-REGULATED BUT INSUFFICIENT GENERATION OF ACTIVATED PROTEIN C IS ASSOCIATED WITH DEVELOPMENT OF MULTI-ORGAN FAILURE IN SEVERE ACUTE PANCREATITIS
- Author
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Reijo Haapiainen, J A Fernandez, Jari Petäjä, Heikki Repo, Pauli Puolakkainen, Leena Kylänpää, J H Griffin, Panu Mentula, Outi Lindström, and Esko Kemppainen
- Subjects
Hepatology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Multi organ ,medicine.disease ,Endocrinology ,Downregulation and upregulation ,Internal Medicine ,medicine ,Cancer research ,Acute pancreatitis ,business ,Protein C ,medicine.drug - Published
- 2005
141. 256 Activation of Circulating CD4+ T-Cells in Preterm Infants with RDS
- Author
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Irmeli Nupponen, Outi Vaarala, R Turunen, Heikki Repo, Sören Andersson, and M Savolainen
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Respiratory distress ,business.industry ,respiratory system ,Systemic inflammation ,eye diseases ,respiratory tract diseases ,Pathogenesis ,Pediatrics, Perinatology and Child Health ,Immunology ,Medicine ,sense organs ,Early activation ,medicine.symptom ,business ,Lymphocyte subsets - Abstract
Background: In preterm infants with respiratory distress syndrome (RDS), early activation of circulating phagocytes is present as a sign of systemic inflammation. Phagocytes interact closely with lymphocytes. The role of lymphocytes in the pathogenesis in RDS is unclear. The aim of this study was to evaluate lymphocyte subsets and their activation during the first postnatal week in preterm infants with and without RDS.
- Published
- 2004
142. 257 Low Proportions of Peripheral Blood TCRãä-Cells in Newborn Infants
- Author
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Sören Andersson, Riikka Turunen, Outi Vaarala, Heikki Repo, Irmeli Nupponen, and M Savolainen
- Subjects
Innate immune system ,business.industry ,T-cell receptor ,Inflammation ,Peripheral blood ,3. Good health ,Very preterm ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,030225 pediatrics ,Pediatrics, Perinatology and Child Health ,Immunology ,Medicine ,medicine.symptom ,business ,Receptor ,Perinatal period ,030217 neurology & neurosurgery - Abstract
Background: Majority of peripheral blood T-cells express the aâT-cell receptor (TCRaâ), which recognizes specific MHC-bound antigens. In the adult, 5–10% of blood T-cells express the TCRaa-receptor. TCRaa-cells recognize antigens in a non-MHC-restricted manner and are part of innate immunity. They are thought to act in defence against microbial pathogens and may play a role in controlling inflammation and preventing chronic inflammatory reactions. Newborn infants, especially those born very preterm, are susceptible to infections. In preterm infants inflammation may play a role in the development of chronic complications. However, little is known about the T-cell subsets in the perinatal period in newborn infants. The aim of this study was to evaluate the TCR aâ and aa -subsets in the peripheral blood in newborn preterm and term infants in comparision with adults.
- Published
- 2004
143. INTRAHEPATIC PROTEIN C ACTIVATION DURING REPERFUSION IN HUMAN LIVER TRANSPLANTATION REDUCES PHAGOCYTE ACTIVATION
- Author
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Jari Petäjä, E J. Pesonen, Krister Höckerstedt, Heikki Mäkisalo, John H. Griffin, Heikki Repo, José A. Fernández, and Minna Ilmakunnas
- Subjects
Transplantation ,medicine.anatomical_structure ,Phagocyte ,Human liver ,business.industry ,Immunology ,Medicine ,business ,Protein C ,medicine.drug - Published
- 2004
144. Neutrophil CD11b Expression and Circulating Interleukin-8 as Diagnostic Markers for Early-Onset Neonatal Sepsis
- Author
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Irmeli Nupponen, Hannu Kautiainen, Anna-Liisa Järvenpää, Heikki Repo, and Sture Andersson
- Subjects
Time Factors ,Neutrophils ,Sensitivity and Specificity ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,030225 pediatrics ,medicine ,Humans ,Prospective Studies ,Interleukin 8 ,Risk factor ,Prospective cohort study ,030304 developmental biology ,0303 health sciences ,Neonatal sepsis ,biology ,CD11 Antigens ,business.industry ,Interleukin-8 ,C-reactive protein ,Infant, Newborn ,Gestational age ,medicine.disease ,3. Good health ,Predictive value of tests ,Pediatrics, Perinatology and Child Health ,Immunology ,biology.protein ,business ,Biomarkers - Abstract
Objective.To assess neutrophil CD11b and circulating interleukin 8 (IL-8) as markers of early-onset infection in neonates.Methods.The study comprised 39 neonates, with a gestational age of 29 to 41 weeks, suspected of infection within 48 hours of life. Neutrophil surface expression of CD11b was quantified with flow cytometry and plasma IL-8 with an enzyme-linked immunosorbent assay. Both data were available from 35 of 39 neonates. Serum C-reactive protein was determined at initial evaluation and, later, on the basis of the clinical picture. Neonates were allocated retrospectively into 2 groups. In the sepsis group (N = 22), 4 had culture-proven sepsis, and 14 had an antenatal risk factor for infection. In the possible-infection group (N = 13), each neonate had a noninfective disorder, but co-occurring infection remained a possibility. Twelve healthy term infants served as controls.Results.CD11b expression and IL-8 levels both increased in order of sepsis > possible infection > healthy. Sensitivity and specificity by the CD11b test for sepsis were equal, at 1.00, and those by the IL-8 test 0.91 and 1.00, respectively; 6 (17.1%) of the 35 neonates had CD11b and IL-8 below cutoff levels.Conclusions.Measuring neutrophil CD11b expression and circulating IL-8 provides a means to identify early-onset neonatal sepsis. The findings may be helpful in planning strategies to safely reduce the use of antimicrobials in neonates.
- Published
- 2001
145. The strip test of procalcitonin in early detection of severe acute pancreatitis
- Author
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Reijo Haapiainen, Esko Kemppainen, Marja-Leena Kylänpää-Bäck, Annika Takala, Heikki Repo, and Pauli Puolakkainen
- Subjects
medicine.medical_specialty ,Strip test ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,Medicine ,Acute pancreatitis ,Early detection ,business ,medicine.disease ,Procalcitonin - Published
- 2001
146. Peripheral blood monocytes from patients with reactive arthritis show normal production of tumour necrosis factor-alpha
- Author
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Pekka Saikku, Marjatta Leirisalo-Repo, Marja Jäättelä, Anneli Lauhio, and Heikki Repo
- Subjects
Adult ,Male ,Letter ,Adolescent ,Immunology ,Tumour necrosis factor alpha ,Infections ,Monocytes ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Immunology and Allergy ,Medicine ,Reactive arthritis ,030304 developmental biology ,030203 arthritis & rheumatology ,0303 health sciences ,Tumor Necrosis Factor-alpha ,business.industry ,Arthritis ,Middle Aged ,medicine.disease ,Peripheral blood ,Female ,business ,Follow-Up Studies - Published
- 1991
147. High Cd11B-Expression In Preterm Infants With RDS
- Author
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Sören Andersson, Heikki Repo, Erkki Pesonen, Maija Pohjavuori, Aila Makela, and Irmeli Nupponen
- Subjects
medicine.medical_specialty ,Obstetrics ,business.industry ,Pediatrics, Perinatology and Child Health ,medicine ,business ,Cd11b expression - Published
- 1999
148. Increased CD11b-Expression in Preterm Infants
- Author
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Irmeli Nupponen, Sture Andersson, Aila Makela, Eero Pesonen, Riikka Parviainen, Heikki Repo, and Maija Pohjavuori
- Subjects
Andrology ,03 medical and health sciences ,0302 clinical medicine ,business.industry ,030225 pediatrics ,Pediatrics, Perinatology and Child Health ,Medicine ,business ,030217 neurology & neurosurgery ,Cd11b expression - Published
- 1999
149. Cord Blood Neutrophils have Higher Adherence than Adult Neutrophils to Cultured Endothelial Cells (HUVEC) 790
- Author
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Irmeli Nupponen, Maija Pohjavuori, Sture Andersson, Eero Pesonen, and Heikki Repo
- Subjects
Andrology ,03 medical and health sciences ,0302 clinical medicine ,business.industry ,030225 pediatrics ,Cord blood ,embryonic structures ,Pediatrics, Perinatology and Child Health ,cardiovascular system ,Medicine ,business ,030217 neurology & neurosurgery ,3. Good health - Abstract
Cord Blood Neutrophils have Higher Adherence than Adult Neutrophils to Cultured Endothelial Cells (HUVEC) 790
- Published
- 1998
150. Systemic inflammatory response syndrome (SIRS) without systemic inflammation
- Author
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S-E Jansson, O Takkunen, Annika Takala, Marjatta Leirisalo-Repo, Heikki Repo, I Jousela, and Klaus T. Olkkola
- Subjects
Systemic inflammatory response syndrome ,Veterinary medicine ,business.industry ,Immunology ,Meeting Abstract ,medicine ,medicine.symptom ,Critical Care and Intensive Care Medicine ,medicine.disease ,business ,Systemic inflammation - Published
- 1998
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