Biomedical subjects

A M Teppo

Publications and source records attributed to A M Teppo.

At least 19 recordsLinked to original sources

PubMed1999

Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes.

Autosomal dominant periodic fever syndromes are characterized by unexplained episodes of fever and severe localized inflammation. In seven affected families, we found six different missense mutations of the 55 kDa tumor necrosis factor receptor (TNFR1), five of which disrupt conserved extracellular disulfide bonds. Soluble plasma TNFR1 levels in patients were approximately half normal. Leukocytes bearing a C52F mutation showed increased membrane TNFR1 and reduced receptor cleavage following stimulation. We propose that the autoinflammatory phenotype results from impaired downregulation of membrane TNFR1 and diminished shedding of potentially antagonistic soluble receptor. TNFR1-associated periodic syndromes (TRAPS) establish an important class of mutations in TNF receptors. Detailed analysis of one such mutation suggests impaired cytokine receptor clearance as a novel mechanism of disease.

Amino Acid Sequence↗

PubMed1999

Immune responses to osteoarticular allografts of the knee--cytokine studies.

Immunological behaviour in correlation with bone allograft survival was studied in peripheral blood and synovial fluid from seven patients who had undergone large bone resection and allograft transplantation of the knee. Plasma and synovial fluid samples for cytokine measurements [interleukin (IL-1beta, IL-6) and tumour necrosis factor alpha (TNF-alpha)] were drawn from peripheral blood for diagnostic arthrocentesis. Two patients were monitored using consecutive sampling up to 12 months postoperatively. Graft survival was considered excellent, but local or diffuse resorption and also fatigue fractures were seen. These findings show that soluble products of T-cell, macrophage and osteoblast origin, produced as a response to the bone-graft antigens, might be responsible for the bone resorption seen in our material. The elevated IL-1beta and TNF-alpha levels detected support this statement.

Adult↗

PubMed1999

High pleural fluid hyaluronan concentrations in rheumatoid arthritis.

Previous studies have shown that high pleural fluid (Pf) hyaluronan (HYA) concentrations may be due not only to malignant mesothelioma but also to inflammatory diseases. The objective of this study was to evaluate Pf-HYA in various nonmalignant inflammatory pleural disorders. A radiometric assay was used to determine HYA in Pf and serum (S) of 126 patients, 12 of whom had rheumatoid arthritis (RA), 22 tuberculosis, 22 pneumonia, 41 lung cancer, 10 malignant mesothelioma and 19 congestive heart failure. Pf-HYA values were correlated with values for Pf-tumour necrosis factor (TNF)-alpha and Pf-interleukin (IL)-1beta, as determined by radioimmunoassay. The highest median Pf-HYA (125.6 mg x L(-1), range 0.04-386.5 mg x L(-1)) occurred in patients with malignant mesothelioma. Among patients with nonmalignant inflammatory diseases, significantly higher median Pf-HYA were observed in those with rheumatoid arthritis (64.2 mg x L(-1), range 25.8-106.9 mg x L(-1)) than in those with tuberculosis (25.5 mg x L(-1), range 14.9-57.1 mg x L(-1), p<0.0005) or pneumonia (20.9 mg x L(-1), range 9.5-129.4 mg x L(-1), p<0.005). There was no correlation between Pf-HYA and S-HYA. Pf-HYA correlated positively with Pf-TNF-alpha (r=0.62) and Pf-IL-1beta (r=0.52). High pleural fluid hyaluronan occurs not only in malignant mesothelioma, but also in certain nonmalignant inflammatory diseases, especially rheumatoid arthritis. One explanation for the increase in pleural fluid hyaluronan may be local production of proinflammatory cytokines, such as tumour necrosis factor-alpha and interleukin-1beta.

Adult↗

PubMed1999

Acute phase response in dairy cows with experimentally induced Escherichia coli mastitis.

Six Finnish Ayrshire cows were challenged intramammarily with 1500 CFU of Escherichia coli (E. coli) into single udder quarters, and the challenge was repeated into contralateral quarters 3 weeks later. All cows received flunixine meglumine once, and 3 of them were also treated with enrofloxacin. At the 2nd challenge, treatments were changed vice versa. The development of mastitis was followed by monitoring of systemic and local clinical signs, and with serial milk and serum samples. Intramammary challenge with E. coli produced clinical mastitis in all cows, the severity of the disease varying greatly between the animals. No significant changes between the 2 treatment regimens or sequent challenges were found for any of the clinical parameters. The response of each cow followed the same pattern after both challenges; three of the cows became mildly and the other 3 either moderately or severely affected. Two severely affected cows had to be euthanized because of severe mastitis. Serum haptoglobin and amyloid-A concentrations peaked 2-3 days after bacterial challenge. Serum haptoglobin did not correlate with the severity of the disease. Serum amyloid-A rose gradually in the severely affected cows, and significant differences were found between severely versus moderately or mildly affected cows at day 4. Serum tumor necrosis factor alpha concentrations increased only in the severely affected cows. Serum cortisol response was prolonged in the severely diseased animals, and was significantly lower after the second challenge. Serum nitrite/nitrate concentration increased in the severely affected cows. This indicated excess nitric oxide production during acute E. coli mastitis. Strongly decreased milk production, and high bacterial growth in the infected quarters were best predictors for the outcome from acute E. coli mastitis.

Acute-Phase Reaction↗

PubMed1998

Does increased urinary interleukin-1 receptor antagonist/interleukin-1beta ratio indicate good prognosis in renal transplant recipients?

BACKGROUND: Interleukin-1 (IL-1) is produced by activated monocytes/macrophages; highly increased amounts of IL-1 have been found in renal tissue in acute rejection of renal grafts. The endogenous inhibitor of IL-1, interleukin-1 receptor antagonist (IL-1ra), is produced in many cells in response to the same stimulus as IL-1. There is some evidence that the balance between IL-1 and IL-1ra is important in the regulation of inflammatory responses. In many inflammatory diseases in both humans and animals, a high concentration of endogenous IL-1ra or administration of exogenous IL-1ra has been shown to relate to shorter recovery time or to reduced mortality. METHODS: We measured the urinary excretion of IL-1ra and IL-1beta during the first 3-6 posttransplant weeks in 23 patients with acute rejection (69 24-hr urine samples) and in 17 patients with stable graft function (51 24-hr urine samples) and expressed the results as cytokine/creatinine ratios. RESULTS: Within the follow-up time, patients with rejection had higher urinary IL-1beta/creatinine (ng/mmol) ratios (median 5.0 vs. 2.7; P<0.005), lower IL-1ra/creatinine (ng/mmol) ratios (median 18.1 vs. 34.2; P<0.1), and consequently lower IL-1ra/IL-1beta ratios (median 3.6 vs. 20.3, P<0.005), compared with patients without rejection. In rejecting patients, IL-1ra/creatinine was constantly low and decreased even further during acute rejection, whereas IL-1beta/creatinine ratios increased from a median prerejection value of 3.5 (range not measurable to 9.0) to a median value of 8.1 (P<0.0005) (range 1.6 to 18.3) during rejection. CONCLUSION: These results suggest that patients who produce high amounts of IL-1ra in relation to IL-1beta are less prone to acute allograft rejection than patients with low IL-1ra/IL-1beta ratios.

Adult↗

PubMed1998

Serum C-reactive protein is rarely lost into urine in patients with secondary amyloidosis and proteinuria.

We studied whether the low serum C-reactive protein (S-CRP) level in patients with inflammatory arthritis and proteinuria was due to the loss of CRP into urine. In 19 patients with secondary amyloidosis (14 with rheumatoid arthritis and five with juvenile chronic arthritis), S-CRP was measured with both immunoturbidimetric and radioimmunoassays. The concentration of urinary CRP was measured with a double-antibody radioimmunoassay. One patient with the most extensive proteinuria (12 g/24 h) excreted CRP at 14 mg/24 h, while in 18 of 19 patients only negligible, if any, amounts of CRP were found in 24-h urine samples. Proteinuria of < 8 g/24 h did not reduce the S-CRP level. Proteinuria exceeding this level may result in increased excretion of CRP into urine and consequently may result in a reduced S-CRP level.

Adolescent↗

PubMed1998

Risk factors for mortality in Type II (non-insulin-dependent) diabetes: evidence of a role for neuropathy and a protective effect of HLA-DR4.

To test the hypothesis that interaction between genetic, immunological, clinical and metabolic risk factors influences the outcome of Type II (non-insulin-dependent) diabetes mellitus, we examined which of the above factors present at baseline were associated with mortality in 134 Type II diabetic patients followed for 9 years. Thirty-eight patients (29%) died during the follow-up period; the majority of whom (68%) died from cardiovascular disease. At baseline, the deceased patients had higher HbA1c values (p = 0.002), higher LDL-triglycerides (p = 0.007), lower HDL-cholesterol (p = 0.007), higher non-esterified fatty acid (NEFA) concentrations (p = 0.014), and higher albumin excretion rate (p < 0.0001) than the patients who survived. In addition, the frequency of HLA-DR4 (21 vs 39%, p = 0.048) and of parietal cell antibodies (5 vs 14%, p = 0.016) were decreased in the deceased as compared to the living patients. Patients who died during follow-up also had more retinopathy (42 vs 16%, p = 0.002), neuropathy (57 vs 23%, p < 0.001), microalbuminuria (45 vs 6%, p < 0.0001), coronary heart disease (50 vs 13%, p < 0.0001), and peripheral vascular disease (27 vs 9%, p = 0.005) at baseline than patients who survived. In a multiple logistic regression analysis macroangiopathy (p = 0.004), neuropathy (p = 0.007), HbA1c (p = 0.018) and albumin excretion rate (p = 0.016) were independent risk factors for death. In patients free of cardiovascular disease at baseline, conventional risk factors such as LDL-cholesterol (p = 0.005) and age (p = 0.003) were associated with subsequent development of cardiovascular disease. In conclusion, in addition to coexisting macroangiopathy, increased albumin excretion rate, poor glycaemic control and neuropathy are risk factors for cardiovascular mortality in patients with Type II diabetes. The presence of HLA-DR4 and signs of autoimmunity may be associated with decreased risk of cardiovascular disease.

Adult↗

PubMed1998

Evaluation of an ELISA test for determination of the serum transferrin receptor. Demonstration of discordance between results obtained with two methods.

We undertook this study to evaluate a recently introduced ELISA kit for determining serum transferrin receptor (TfR) concentration (TfR, Ramco Laboratories, Inc.), to produce reference values for healthy adults, and to compare the results with another commercially available reagent system. The mean (SD) recovery of added TfR was 88% (6%). In dilution studies, the ratio between the measured and expected values was 0.98 (0.11). The intra-assay and interassay coefficients of variation were from 5% to 7% and from 6% to 9% in a physiological and a supraphysiological concentration range, respectively, and from 13% to 16% in a subnormal concentration range. In healthy adults between 20 and 60 years of age, we observed no age- or sex-related differences in TfR values. Thus, the same reference interval, 3.0-8.2 mg l(-1), may be used for this population. The correlation between the results obtained with the Ramco TfR test and the Amgen Diagnostics Clinigen test was satisfactory (r=0.79). The Ramco TfR test produced higher values (Tf=0.40 (-0.45-1.25)+1.46 (1.16-1.75)* Clinigen). The number of samples that fell within the same concentration interval with both methods (low, normal or high in relation to the respective reference interval) was only 45% (27/60). The Ramco TfR test had fewer values falsely suggesting iron deficiency than the Clinigen test. Serum TfR methods need to be uniformly standardized.

Adult↗

PubMed1998

Adhesion molecules and urinary tumor necrosis factor-alpha in idiopathic membranous glomerulonephritis.

Adhesion molecules are required in several physiological processes, but their altered function/expression is associated with the pathogenesis of inflammatory diseases. In the present study on idiopathic membranous glomerulonephritis (MGN) the expression of adhesion molecules (ICAM-1, VCAM-1, PECAM-1, E-selectin, LFA-1, Mac-1) was analyzed in different cellular compartments of the kidney using an indirect immunoperoxidase technique and monoclonal antibodies. Relationships between the expression of these molecules and the clinical and morphological activity of the disease and the urinary excretion of tumor necrosis factor alpha (TNF-alpha) were studied in 20 patients. The results were compared with the findings in ten normal kidneys and urinary TNF-alpha in 17 healthy subjects. The expression of adhesion molecules in glomeruli and tubules was unchanged apart from a diminished expression of VCAM-1 (P = 0.014) in glomerular parietal epithelial cells and PECAM-1 in glomerular endothelial cells (P < 0.01). Interstitial peritubular capillaries expressed significantly (P = 0.009) more E-selectin compared with the controls. The interstitial compartment had a highly increased number of cells expressing ICAM-1 in MGN (32.4 +/- 4.6 cells/high power field) compared with the controls (9.4 +/- 1.2; P < 0.001). Also, cells expressing VCAM-1 (10.2 +/- 1.6 vs. 2.8 +/- 1.9; P = 0.005). PECAM-1 (25.9 +/- 5.3 vs. 7.4 +/- 2.1; P = 0.006), and LFA-1 (20.4 +/- 3.6 vs. 8.3 +/- 1.5; P = 0.041) were increased in the interstitium. Proteinuria correlated particularly with the expression of E-selectin in peritubular capillaries (r = 0.63, P = 0.004). The number of LFA-1 expressing inflammatory cells in the interstitium correlated with peritubular capillary E-selectin (r = 0.8, P < 0.001) and interstitial ICAM-1 (r = 0.61, P = 0.009) expression, but histological alterations did not correlate with the expression of adhesion molecules. Tumor necrosis factor-alpha excretion was significantly increased in MGN (41 +/- 8 pg/mg creatinine) compared with the controls (13 +/- 2; P = 0.001), and in particular, it correlated with the interstitial expression of LFA-1 (r = 0.71, P = 0.002). This study suggests that active MGN leads not only to proteinuria but also to increased urinary TNF-alpha excretion. These may serve as triggers for the up-regulation of adhesion molecules in the peritubular capillaries and interstitial cells thus enhancing the development of the interstitial injury.

Adult↗

PubMed1997

Release of TGF-beta 1 and VEGF in tears following photorefractive keratectomy.

PURPOSE: To study the presence and release of tear fluid transforming growth factor-beta 1 (TGF-beta 1) and vasoendothelial growth factor (VEGF) of 19 patients undergoing excimer laser photorefractive keratectomy. METHODS: Tear fluid samples were collected with scaled microcapillary tubes preoperatively (Day 0) and on the first or second (Day 1-2) and seventh (Day 7) postoperative days. Since postoperative tear fluid flow was significantly higher, we calculated the release of both growth factors by multiplying the concentration by the tear fluid flow in the capillary. RESULTS: The median tear fluid flow in the capillary was 8.1 microliters/ min (range 0.7-20.8) on Day 0, 46.3 microliters/min (3.1-135.1) on Day 1-2, and 10.2 microliters/min (1.8-65) on Day 7. The median TGF-beta 1 concentration and release values were: Day 0: 4.5 ng/ ml (0-23) and 24 pg/min (0-257), Day 1-2: 9 ng/ml (0-32) and 446 pg/min (0-4602; p = 0.0014), and Day 7: 6.5 ng/ml (0-44) and 53 pg/min (0-470), respectively. The median VEGF concentrations and releases were: Day 0: 19 ng/ml (14-23) and 128 pg/min (11-458), Day 1-2: 15 ng/ml (11-20) and 695 pg/ min (14-2567; p = 0.0007), and Day 7: 17.5 ng/ml (15-22) and 167 pg/min (27-1235), respectively. CONCLUSIONS: TGF-beta 1 and VEGF are components of normal tear fluid. The significantly increased release of both growth factors after exeimer laser photorefractive keratectomy may influence the corneal wound healing process.

Adult↗

PubMed1997

Platelet-derived growth factor-BB (PDGF-BB) in tear fluid: a potential modulator of corneal wound healing following photorefractive keratectomy.

PURPOSE: To measure the pre- and postoperative tear fluid platelet-derived growth factor-BB (PDGF-BB) concentrations of patients undergoing excimer laser photorefractive keratectomy (PRK). METHODS: Tear fluid samples from PRK patients were collected with scaled microcapillary tubes preoperatively (Day 0, N = 23), on the second (Day 2, N = 24) and on the seventh (Day 7, N = 14) postoperative days. The PDGF-BB concentration was measured using a sandwich enzyme immunoassay, and the PDGF-BB release was calculated by multiplying the concentration by the tear fluid flow in the collection capillary. RESULTS: The mean tear fluid flow in the capillary was 17.4 microliters/ min (range 1.4-55.0) on Day 0, 62.6 microliters/min (4.3-125.0, p = 0.0000) on Day 2, and 15.5 microliters/min (1.2-50.0, NS) on Day 7. Seventeen percent (4/23) of the Day 0 samples contained detectable concentrations of PDGF-BB (range 95-1330 ng/l). On Day 2 all (24/24) tear samples showed significantly increased concentrations (mean 507 ng/l, range 45-2280 ng, p = 0.0001) and releases (mean 27.6 pg/min, range 1.0-98.0; p = 0.0000). On Day 7 PDGF-B was still measurable in 9/14 samples (mean concentration 194 ng/l, range < 5-925 ng/l, and mean release 1.9 pg/min, range 0.04-6.8 pg/min). CONCLUSIONS: PDGF-BB is an inducible component of tear fluid. In spite of hypersecretion caused by the corneal wound, PDGF-BB concentrations raised significantly during the initial wound healing. Increased PDGF-BB release during the two postoperative days following PRK suggests a role in corneal wound healing.

Adult↗

PubMed1997

Urinary transforming growth factor-beta 1 in membranous glomerulonephritis.

BACKGROUND: Human idiopathic membranous glomerulonephritis (MGN) has a highly variable clinical course and factors determining its outcome are poorly known. Since transforming growth factor-beta 1 (TGF-beta 1) has an essential role in renal fibrogenesis, we studied the possibility to use urinary excretion of TGF-beta 1 in the assessment of progression of the disease in patients with MGN. METHODS: Urinary TGF-beta 1 was determined in 41 patients with MGN, 25 healthy subjects, six non-proteinuric renal transplant patients, 10 patients with IgA glomerulonephritis, and seven proteinuric patients (with non-progressive diseases) using a novel, double antibody enzyme immunoassay. The results were compared with renal morphology and clinical indices of activity of MGN over 12 months. RESULTS: The median urinary TGF-beta 1 excretion (pg/mg creatinine) was significantly higher (1730; range 60-16,970) in MGN patients than in the healthy controls (300; 30-1330; P < 0.0001). In renal allograft recipients the excretion was 840 (250-3440; P < 0.0001 vs healthy controls), in IgA GN it was 1130 (30-4910; P = 0.039), and in proteinuric patients it was 39 (29-165; P = NS). In MGN but not in the proteinuric controls or renal allograft recipients, urinary TGF-beta 1 correlated with urinary albumin excretion (r = 0.86, P < 0.0001) but no correlation with renal function or the duration of the disease was found. Urinary TGF-beta 1 at renal biopsy correlated with interstitial cellular inflammation and its excretion 1 year before the biopsy correlated with indices of sclerosis/fibrosis. Immunosuppressive therapy significantly decreased urinary TGF-beta 1 from 2800 (1610-16,960) to 840 (170-1600) pg/mg creatinine (P = 0.028). Patients with persistent nephrotic syndrome and/or declining renal function had a higher initial TGF-beta 1 excretion (median 3680; 1830-7420 pg/mg creatinine) than those entering partial or complete remission (1060; 60-1960; P = 0.003) within 12 months from sampling.

Adult↗

PubMed1997

Mesangial glomerulonephritis as an extra-articular manifestation of rheumatoid arthritis.

Mesangial glomerulonephritis (MesGN) is a frequent renal biopsy finding in patients with rheumatoid arthritis (RA) presenting with haematuria and/or proteinuria. The purpose of this study was to describe the mesangial immunofluorescence (IF) findings in 37 such RA patients, and to correlate the nature of the glomerular immunodeposits with clinical data, levels of serum immunoglobulins and the concentrations of serum rheumatoid factors (RFs). The serological findings in RA patients with MesGN were correlated with those of RA patients matched for age, sex and duration of RA, but without clinically evident renal disease. The most characteristic mesangial IF finding in 37 RA patients with MesGN was IgM observed in 29 specimens (78%). IgA (n = 16) and C3 (n = 15) deposits were also frequently found, whereas C1q (n = 3) and IgG (n = 2) deposits were only occasionally seen. Two main patterns of IF findings could be classified. (1) Granular IgM deposits as a sole or main finding (IgM GN; 25 specimens). The intensity of the mesangial IgM deposits did not correlate with the duration or severity of RA nor with the levels of serum immunoglobulins. However, a significant correlation with the intensity of mesangial IgM deposits and the levels of serum IgM class RF was observed. (2) Granular IgA deposits usually together with the complement component C3, i.e. IgA glomerulonephritis (IgA GN; nine specimens). The intensity of mesangial IgA deposits correlated significantly with the duration and severity of RA, and especially with serum IgA levels. Both RA patients with IgA GN or IgM GN were associated with a more frequent occurrence and higher titres of serum RFs when compared with the RA patients without nephropathy. The clinicopathological correlations and the association with RF support the concept that MesGN is related to the basic rheumatoid disease, and it should be regarded as an extra-articular manifestation of RA.

Adult↗

PubMed1997

Increased release of tumour necrosis factor-alpha in human tear fluid after excimer laser induced corneal wound.

AIMS: To measure the pre- and postoperative tear fluid tumour necrosis factor-alpha (TNF-alpha) concentration and release in patients undergoing excimer laser photorefractive keratectomy (PRK). METHODS: Tear fluid samples from 18 PRK patients were collected with scaled microcapillary tubes preoperatively (day 0), on the second (day 2), and on the seventh (day 7) postoperative days. The TNF-alpha concentration was measured using a double antibody radioimmunoassay, and the TNF-alpha release was calculated by multiplying the concentration by the tear fluid flow in the collection capillary. RESULTS: The mean tear fluid flow in the capillary was 22.5 microliters/min (range 1.5-93.2) on day 0, 80.7 microliters/min (3.0-219, p = 0.0002) on day 2, and 14.6 microliters/min (1.8-41.7, NS) on day 7. The mean TNF-alpha concentration and release values were: day 0, 358 ng/I (110-680) and 9.5 pg/min (0.2-37.5, NS); day 2, 417 ng/l (< 5-750, NS) and 28.6 pg/min (0.6-81.5; p = 0.003); and day 7, 320 ng/I (< 5-735, NS) and 4.8 pg/min (0-25.4, NS), respectively. CONCLUSION: TNF-alpha appears to be a component of normal tear fluid. In spite of hypersecretion caused by the corneal wound, TNF-alpha concentrations remain constant during wound healing. TNF-alpha release increases significantly during the 2 postoperative days following PRK, suggesting a role in corneal wound healing.

Adult↗

PubMed1997

Elevated circulating levels of inflammatory cytokines in patients with abdominal aortic aneurysm.

The basic feature in the pathogenesis of abdominal aortic aneurysm (AAA) is the degradation of extracellular matrix components. This process is induced partly by cytokines secreted from inflammatory and mesenchymal cells. Circulating levels of inflammatory cytokines were studied in AAA patients and compared with subjects suffering from atherosclerotic disease only. Furthermore, the predictive value of cytokine concentrations was evaluated for aneurysm expansion rate. Circulating levels of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) were measured in 50 AAA patients (40 men, 10 women), 42 patients with coronary heart disease (CHD) (23 men, 19 women), and 38 controls whose angiogram was normal (17 men, 21 women). No differences in cytokine concentrations were found between the CHD patients and the controls. AAA disease was found to be associated with significantly higher IL-1 beta and IL-6 concentrations in both male patients (median concentrations of 19.40 pmol/L and 6.45 pmol/L, respectively) and female patients (19.26 pmol/L and 7.99 pmol/L) than in either the CHD patients or the controls (P < .005). TNF-alpha levels were slightly higher in the AAA patients (1.64 pmol/L in the males and 1.59 pmol/L in the females) than in the other groups (P < .05). IFN-gamma levels were elevated significantly in the female AAA patients (3.75 pmol/L) compared with levels found in the other female (P < .05) or male (P < .01) patient groups. The measured cytokine concentrations were not related to the size of the aneurysm or the maximal thickness of the thrombus within the aneurysm. IFN-gamma concentration showed a significant positive correlation to the aneurysm expansion (R = .37, P < .02) and negative correlation to the concentration of aminoterminal propeptide of type III procollagen during 6-month follow up (R = -.42, P < .005). The results show that circulating levels of inflammatory cytokines are elevated in patients with AAA disease, suggesting that the production of these cytokines is increased in these patients compared with CHD patients and controls. Elevated INF-gamma concentrations seem to predict an increased rate of expansion in AAA.

Aortic Aneurysm, Abdominal↗

PubMed1997

Urinary excretion of TGF-beta 1, PDGF-BB and fibronectin in insulin-dependent diabetes mellitus patients.

We studied the urinary excretion of transforming growth factor-beta 1 (TGF-beta 1), platelet-derived growth factor-BB (PDGF) and fibronectin (FN) in 104 patients (52 normoalbuminuric, 24 microalbuminuric, and 28 with overt diabetic nephropathy) with insulin-dependent diabetes mellitus (IDDM) of a long duration and in 30 non-diabetic controls. IDDM patients had higher urinary excretion of TGF-beta 1, PDGF and FN compared to controls. Urinary excretion of TGF-beta 1 and PDGF was elevated in all IDDM subgroups, while FN excretion was significantly increased only in patients with macroalbuminuria. Urinary excretion of TGF-beta 1 and FN did not differ between normoalbuminuric IDDM patients with long duration of diabetes, a group at low risk of ever developing diabetic nephropathy, and IDDM patients with incipient or overt diabetic nephropathy. Excretion of PDGF was significantly higher in patients with micro- and macroalbuminuria compared to normoalbuminuric patients, but there was a considerable overlap between the groups. In conclusion, although longitudinal follow-up studies are needed to further clarify the issue, our results in long-standing IDDM do not support a hypothesis of urinary excretion of TGF-beta 1, PDGF or FN to predict development of diabetic nephropathy.

Adult↗

PubMed1996

Growth of Chlamydia pneumoniae in cultured human peripheral blood mononuclear cells and induction of a cytokine response.

In vitro infection of freshly isolated human peripheral blood mononuclear cells (HPBMC) with Chlamydia pneumoniae was found to induce a production of tumour necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and interferon alpha (IFN-alpha). The secretion was dependent on the amount of infecting chlamydiae and most of it occurred during the first 12 to 24 h. Lipopolysaccharide (LPS) of Salmonella minnesota Rechemotype, used as a positive control for HPBMC activation, induced a release of TNF-alpha, IL-1 beta and IL-6, but not of IFN-alpha, similar to the effect of C. pneumoniae. Viable chlamydiae could not be recovered from HPBMCs infected immediately after their isolation, whereas HPBMCs which were cultured in vitro for 3 to 9 days before infection were able to maintain the growth of C. pneumoniae. Growth inside HPBMCs as well as induction of cytokine response may have a role in the pathogenesis of C. pneumoniae infection.

Chlamydia Infections↗

PubMed1996

Increased serum neutral endopeptidase activity in acute renal allograft rejection.

Neutral endopeptidase (EC 3.4.24.11; NEP), originally isolated from renal tubular brush border, is a cell surface peptidase identical to the CD10 antigen (or CALLA; common acute lymphoblastic leukemia antigen) in lymphoid cells. We studied the serum NEP levels daily after transplantation (Tx) in 19 renal allograft recipients. The NEP activity was determined with a two-step enzymatic assay utilizing a fluorogenic substrate (Suc-Ala-Ala-Phe-AMC; see text) and related to clinical signs of graft rejection, to signs of immunoactivation in transplant fine-needle aspiration biopsy (FNAB) specimens, to renal function, and to serum levels of C-reactive protein. The serum NEP levels remained normal (peak level 10.3 +/- 1.8 micrograms/l on days 6-9 after Tx, initial level after Tx 7.3 +/- 1.4 micrograms/1 on day 2; mean values +/- SEM) in patients who neither showed clinical signs of rejection nor had findings of immunoactivation in FNAB samples. On the contrary, the serum NEP levels rose clearly in patients developing acute rejection verified clinically and in FNAB samples (peak value 90.4 +/- 18.7 micrograms/l on days 6-9 post-Tx; p < 0.001 compared with patients without sings of immunoactivation) and even in patients having immunoactivation in FNAB without clinical evidence of rejection (108.2 +/- 22.4 micrograms/l, p < 0.001). Serum NEP peak appeared 2-3 days before clinical diagnosis of rejection and a positive findings in FNAB samples. Serum NEP increments did not correlate with changes in serum creatinine, delayed onset of renal excretory function, blood leukocyte count, C-reactive protein level, or infections. Thus, the serum NEP activity was shown to increase after renal allotransplantation associated with early phases of immunoactivation and development of acute graft rejection. Because of the limited number of patients studied, the clinical implications of these preliminary observations for kidney transplant monitoring clearly need confirmation in larger studies.

Adolescent↗