Search PubMed⌕ Search

Biomedical subjects

J Risteli

Publications and source records attributed to J Risteli.

At least 199 records · Page 11Linked to original sources
PubMed1991

Synthesis of type I collagen in healing wounds in humans.

To quantify wound healing in surgical patients, samples of wound fluid were collected through a silicone rubber tube for 7 postoperative days and their concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) were measured with specific radioimmunoassays. The mean concentration of PICP in would fluid on day 1 was 207 +/- 92 (SD) micrograms/L, and on day 2 908 +/- 469 micrograms/L (p less than 0.001, signed rank test). On day 7, the mean concentration reached was 380 times higher than that of day 1 (79,330 +/- 54,151 micrograms/L). Only one peak of PICP antigenicity, corresponding to the intact propeptide as set free during synthesis of type I procollagen, was detected on Sephacryl S-300 gel filtration analysis of wound fluid samples. The mean concentration of PIIINP was 70 +/- 61 micrograms/L on day 1, 86 +/- 88 micrograms/L on day 2, and 180 +/- 129 micrograms/L on day 3 (p less than 0.001 when compared with day 1). Finally on day 7, a 250-fold concentration (17,812 +/- 9839 micrograms/L), compared with day 1, was reached. Methods described in the present paper allow separate and repetitive quantification of the synthesis of both type I and type III procollagen during human wound healing.

Adult↗
PubMed1991

Markers of collagen and basement membrane metabolism in sera of patients with progressive systemic sclerosis.

The concentrations of the amino terminal propeptide of type III procollagen, the 7S domain of type IV collagen, and the fragment P1 of laminin (PIIINP, 7S, and P1 respectively) and the activity of galactosylhydroxylysyl glucosyltransferase (GGT) in serum were evaluated as indicators of disease activity in a cross sectional study of 84 patients with progressive systemic sclerosis. The mean values of PIIINP, P1, and GGT were raised in progressive systemic sclerosis, 19-32% of patients having abnormal values of the various tests. PIIINP, measured with two different assays, and P1 were associated with active, acute, or subacute disease. GGT also correlated positively with some acute phase proteins in the whole group, without a clear association with the course of the disease. Arthritis was associated with increased PIIINP concentrations as well as with an increased activity of GGT. Kidney disease led to raised concentrations of the degradation products of PIIINP. Raynaud's phenomenon in the hands was related to increased PIIINP concentrations.

Adult↗
PubMed1991

Thrombolytic therapy with streptokinase stimulates collagen breakdown.

BACKGROUND: Plasmin is capable of degrading extracellular matrix components such as collagen in vitro. To evaluate the significance of this for in vivo conditions, we set out to study the effect of streptokinase, which acts by converting plasminogen to plasmin, on the serum concentrations of the amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy-terminal propeptide of type I procollagen (PICP). METHODS AND RESULTS: Twenty-three patients with suspected acute myocardial infarction were included in the study; 17 of them received thrombolytic therapy, and six were treated conservatively. PIIINP and PICP were assayed with radioimmunoassays. Kinetics of creatine kinase-MB release were determined to differentiate reperfusers from nonreperfusers. Composite curves of creatine kinase-MB release were constructed for different patient subgroups. During streptokinase infusion the serum concentrations of PIIINP increased rapidly, with a maximum mean increase of 50% (from 2.2 +/- 0.2 to 3.3 +/- 0.3 micrograms/l) in 45 minutes. A similar increase was also observed in two patients who received thrombolytic therapy but did not subsequently develop any myocardial infarction determined on the basis of enzyme release. The relative increase in PIIINP during streptokinase treatment was higher in those acute myocardial infarction patients with probable reperfusion than those with nonprobable reperfusion. Corresponding changes in PIIINP were not seen in the control group. Two days later there was a second increase in serum PIIINP for both patient groups. This change coincided with a similar increase in PICP. CONCLUSIONS: We conclude that streptokinase, probably by activation of plasminogen to plasmin, stimulates the breakdown of type III collagen during thrombolytic therapy. This phenomenon may decrease the risk of rethrombosis of the affected artery if the exposed collagen is responsible for thrombosis formation, but it could also be involved in the development of hemorrhagic complications during thrombolytic therapy. The second increase in PIIINP levels probably indicates type III collagen synthesis of the infarcted area. This investigation represents a pilot study, and more studies on the effects of various thrombolytic agents on interstitial collagen metabolism are obviously needed.

Collagen↗
PubMed1991

Serum concentrations of the type I and III procollagen propeptides as biochemical markers of growth velocity in healthy infants and children and in children with growth disorders.

The reproducibility and specificity of a new, rapid, simple RIA for measuring the concentration of the soluble carboxypropeptide of type I procollagen (PICP) in serum was confirmed. Serum PICP was determined in 442 healthy Caucasian subjects ranging in age from 3 wk to 18 y. Highest PICP values (mean +/- SD: 2200 +/- 350 micrograms/L) occurred in infants less than 3 mo of age, falling by 70% at 2 y and by an additional 10% at 4 y. There was no significant change in serum PICP between 4 and 16 y of age (330 +/- 130 micrograms/L), but a decrease to adult levels of less than 160 micrograms/L occurred by 18 y. In 76 children with growth disorders, serum PICP was related to linear growth velocity (p less than 0.001), although there were no significant differences in PICP among the 38 children with growth hormone insufficiency, the 21 short children with no endocrinologic abnormality, or the 17 tall children. All 15 prepubertal children treated with growth hormone for 3 mo showed significant increases in both growth velocity and serum PICP, with a significant relationship (p less than 0.01) between the degree of increases. The rise in serum PICP at 3 mo (but not baseline PICP values) predicted the increase in growth velocity after 1 y of treatment. Similar changes were observed in the concentration of the aminopropeptide of type III procollagen, except that serum aminopropeptide of type III procollagen showed a definite increase during puberty and a wider spread of values in growth disorders. We conclude that measuring serum PICP by the new, reproducible assay reflects height velocity in prepubertal children and may be a useful biochemical means of monitoring growth rates.

Adolescent↗
PubMed1991

Type I and III procollagen propeptides in growth hormone-deficient patients: effects of increasing doses of GH.

The effect of increasing doses of growth hormone on collagen synthesis in GH-treated GH-deficient patients was determined in a short-term study. The synthesis of type I and III collagen was estimated by measurements of the carboxyterminal propeptide of type I procollagen and the aminoterminal propeptide of type III procollagen. Type I collagen is mainly found in bone and type III collagen in loose connective tissue. We observed a GH dose dependency of both procollagen propeptides. Serum type I procollagen propeptide was significantly higher following GH doses of 4 and 6 IU/day for 14 days compared with 2 IU/day (normal replacement dose) (p = 0.04). Withdrawal of GH therapy for 14 days resulted in wider variation, but not significantly different from the levels at 2, 4 and 6 IU/day. A dose dependency was found regarding type III procollagen propeptide, showing significantly higher serum concentrations at a GH dose of 4 IU/day compared with 2 IU/day (p = 0.001), and of 6 IU/day compared with 4 IU/day (p = 0.001). Withdrawal of GH therapy resulted in significantly lower type III procollagen propeptide concentrations compared with those at a GH dose of 4 and 6 IU/day (p = 0.03). Serum type III procollagen propeptide increased twice as much as type I procollagen propeptide, by 47 vs 25%, at a GH dose of 6 IU/day compared with 2 IU/day. The differences between the effects on type I and type III collagen may reflect differences in secretion or turn-over rate of collagen in bone and loose connective tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Connective tissue metabolism and alcohol intake in alcoholic liver disease.

We have examined the relationship between blood markers of fibrogenesis and basement membrane formation and alcohol intake in patients with a wide range of clinical and histological severity of alcoholic liver disease (Niemelä et al., 1990). While the patients with a mean of less than 8 mM alcohol in morning urines (mild or moderate drinkers) had a significant (p < 0.00001) decrease in serum aminoterminal propeptide of type III procollagen, type IV collagen and laminin in a period of 27 +/- 1 weeks, the patients with more than 8 mM of urinary alcohol (heavy drinkers) had no improvement. There was also a significant decrease in serum gamma glutamyl transferase activity in the group with lower, but not in that with the higher urinary alcohol concentrations. The Combined Clinical and Laboratory Index (CCLI) decreased in both groups, although the recovery was significantly (p < 0.03) greater in those with the lower urinary alcohol levels (66% +/- 6%) than in the group with a urinary alcohol level of > or = 8 mM (28% +/- 15%). We suggest that connective tissue metabolism in alcoholic liver disease is closely related to alcohol intake and thus affects the prognosis of the alcoholic patient.

Alcohol Drinking↗
PubMed1991

Carboxyterminal propeptide of type I procollagen in cerebrospinal fluid in childhood and in children with leukemia undergoing intrathecal treatment.

We determined the reference interval for the carboxyterminal propeptide of type I procollagen (PICP), an indicator of the synthesis of type I collagen, in cerebrospinal fluid (CSF) by studying 32 infants and children, ages less than or equal to 15 years. The concentration of PICP is age dependent, with particularly high concentrations occurring in children younger than 1.5 years. In older children the concentration is stable (reference interval 20-92 micrograms/L). We also investigated the possibility that PICP in CSF could reflect local fibroproliferative changes in the arachnoid in a cohort of 42 children with acute lymphoblastic leukemia who were monitored by repeated sampling in connection with intrathecal therapy. Initially, there was no difference in PICP between the children with newly diagnosed leukemia and the controls. PICP concentrations were significantly higher (P less than 0.01) during intrathecal methotrexate therapy, with median values above the reference interval. Continuous corticosteroid treatment was associated with a significant decrease in PICP (P less than 0.02 and P less than 0.01, respectively, in two groups treated according to different protocols), close to the lower limit of the reference interval. Intrathecally administered methotrexate and systemic corticosteroid treatment are known to be associated with the development of arachnoiditis and with general repression of collagen synthesis, respectively. We conclude that PICP in CSF is a sensitive indicator of local fibroproliferation and ongoing collagen synthesis.

Adolescent↗
PubMed1991

Use of various epithelial tumor markers and a stromal marker in the assessment of cervical carcinoma.

The epithelial cell tumor markers squamous cell carcinoma antigen, CA 125, CA 15-3, and TAG 72, and the aminoterminal propeptide of type III procollagen, an indicator of collagen metabolism, were evaluated in 111 cervical carcinoma patients. Squamous cell carcinoma antigen was pathologic in 47%, aminoterminal propeptide of type III procollagen in 40%, CA 125 in 13%, CA 15-3 in 30%, and TAG 72 in 9% of the 91 patients with squamous cell carcinoma. The squamous cell carcinoma antigen, aminoterminal propeptide of type III procollagen, and CA 125 correlated with the clinical stage. The predictive value of a pathologic squamous cell carcinoma antigen was 78% and that of a negative result 68%. Squamous cell carcinoma antigen and aminoterminal propeptide of type III procollagen further increased the detection rate by approximately 20% from that obtained by squamous cell carcinoma antigen alone. In 16 patients with advanced disease, squamous cell carcinoma antigen correlated with the behavior of the disease in eight, aminoterminal propeptide of type III procollagen in nine, and CA 125 in six patients. Pathologic squamous cell carcinoma antigen, CA 125, CA 15-3, TAG 72, and aminoterminal propeptide of type III procollagen appeared in 11, 32, 31, 31, and 47% of 19 patients with adenocarcinoma, respectively. Squamous cell carcinoma antigen is clinically useful in squamous cell carcinoma but poor in adenocarcinoma, for which the other markers are better. Squamous cell carcinoma antigen, CA 125, and aminoterminal propeptide of type III procollagen may be used for monitoring the behavior of advanced squamous cell carcinoma.

Adenocarcinoma↗
PubMed1990

Serum concentrations of CA 125 and aminoterminal propeptide of type III procollagen (PIIINP) in patients with endometrial carcinoma.

Serum CA 125 (a marker of coelomic epithelial cells) and aminoterminal propeptide of type III procollagen (PIIINP; an indicator of collagen metabolism) concentrations were measured in 148 patients with endometrial carcinoma. An initial serum concentration of CA 125 was pathologic in 17% of the patients, the frequency of abnormal values being higher (P = 0.0001) in advanced (63%) than in early disease (10%). The serum PIIINP concentration was increased in 35% of the patients and more often (P less than 0.05) so in advanced (63%) than in early disease (31%). Among all the patients, at least one of the tumor markers was increased in 43% of the cases. In early disease 12 of 108 patients contracted recurrent cancer. The accuracy of the pathologic CA 125 (9%) and PIIINP (18%) concentrations in their prediction was poor. In the total material, pathologic CA 125 and PIIINP concentrations appeared simultaneously in 11 patients, of whom eight had poor prognoses. In monitoring of treatment response of 24 patients, regression was accompanied by normal or decreasing CA 125 and PIIINP values. The persistence of pathologic CA 125 and/or PIIINP concentration predicted relapse of the malignancy. In progressive disease, CA 125 and PIIINP concentrations together or separately remained at a pathologic level or increased continuously. In clinically stable endometrial carcinoma, CA 125 gave false-negative results in 71% of the determinations and PIIINP only in 12%. The current results suggest the use of CA 125 and PIIINP, simultaneously, in monitoring the clinical course of advanced endometrial carcinoma.

Adult↗
PubMed1990

Circulating C-terminal propeptide of type I procollagen is cleared mainly via the mannose receptor in liver endothelial cells.

The fate of the circulating C-terminal propeptide of type I procollagen (PICP) was studied. Trace amounts of 125I-PICP administered intravenously to rats disappeared from the blood with an initial t1/2 of 6.1 min. After 45 min the radioactivity was distributed as follows: liver, 36%; blood, 23%; kidneys, 18%; urine, 20%; spleen, 1%; lungs, 2%; heart, 0.4%. To prevent escape of label from the site of uptake, PICP was labelled with 125I-tyramine cellobiose (125I-TC), which is trapped intralysosomally. With this ligand a serum t1/2 of 8.7 min was recorded, and 70% and 20% was traced in the liver and kidneys respectively. The uptake per liver endothelial cell (LEC) was 1000 times that per parenchymal cell and twice that per Kupffer cell. At 1 h and 6 h after addition of 125I-PICP to cultured LEC, 15% and 45% respectively, had been endocytosed. Only ligands for the mannose receptor could compete with PICP for endocytosis. To study whether the same specificity was operative in vivo, 125I-PICP was injected along with an excess of ovalbumin, which is known to be endocytosed by the mannose receptor of LEC. The serum t1/2 was prolonged from 6 to 16 min, signifying that terminal mannose residues are an important signal for clearance of PICP. In conclusion, these studies show that LEC constitute the main site of uptake of circulating PICP. The uptake is mediated by endocytic receptors which recognize terminal mannose residues.

Binding, Competitive↗
PubMed1990

Chlorate inhibits tyrosine sulfation of human type III procollagen without affecting its secretion or processing.

Sodium chlorate, a potent inhibitor of sulfation reactions, completely inhibits the formation of tyrosine-o-sulfate in type III procollagen in human fibroblasts, when used in concentrations that do not affect the incorporation of radioactive amino acids into protein. The unsulfated type III procollagen is secreted into the medium at a rate comparable, to those of sulfated type III procollagen and type I procollagen, which normally does not undergo sulfation. The enzymatic cleavage of the aminoterminal propeptide of type III procollagen is incomplete in fibroblast cultures, irrespective of the sulfation status of the protein.

Cells, Cultured↗
PubMed1990

Collagen metabolism in gynecologic patients: changes in the concentration of the aminoterminal propeptide of type III procollagen in serum.

We have previously found the serum concentration of the aminoterminal propeptide of type III procollagen, an indicator of collagen metabolism, to be increased in advanced ovarian cancer. In this study we measured the serum aminoterminal propeptide of type III procollagen concentration in healthy women during the menstrual cycle and in patients with salpingo-oophoritis, leiomyomas, endometriosis, and benign ovarian tumors. The concentration was higher in the luteal phase than that in the follicular phase, suggesting an association of collagen metabolism with ovarian steroid hormones. Severe salpingo-oophoritis increased the serum level of the aminoterminal propeptide of type III procollagen with a decrease to normal during recovery. Elevated values were occasionally seen in endometriosis and leiomyomas. These findings indicate that the aminoterminal propeptide of type III procollagen is a relatively unspecific indicator of ovarian carcinoma.

Adult↗
PubMed1990

Markers of fibrogenesis and basement membrane formation in alcoholic liver disease. Relation to severity, presence of hepatitis, and alcohol intake.

This study investigated the relationships of the serum markers of fibrogenesis and basement membrane formation to the clinical and morphological severity of alcoholic liver disease and to the degree of alcohol abuse. The concentrations of the aminoterminal propeptide of type III collagen, type IV collagen, and laminin were measured from 87 samples representing a wide range of clinical and histological severities of the disease, which were assessed with indices that have been shown to correlate well with the risk of dying within 1 yr. Significant correlations (p less than 0.00001) were found between the markers of connective tissue metabolism and the Combined Clinical and Laboratory Index: (aminoterminal propeptide of type III collagen, rs = 0.82; type IV collagen, rs = 0.82; laminin, rs = 0.81), as well as between these markers and the Combined Morphological Index: (aminoterminal propeptide of type III collagen, rs = 0.70; type IV collagen, rs = 0.68; laminin, rs = 0.64). Whereas the patients with less than 8 mM of alcohol in their morning urine (mild or moderate drinkers) showed a significant (p less than 0.00001) decrease in these markers in a period of 27 +/- 1 wk, the patients with more than 8 mM of urinary alcohol (heavy drinkers) had no improvement. It is proposed that both fibrogenesis and basement membrane formation are associated with disease severity, degree of alcoholic hepatitis, and alcohol intake, which are important determinants of prognosis in alcoholic liver disease.

Alcohol Drinking↗
PubMed1990

Immunohistochemical evidence that lung carcinomas grow on alveolar basement membranes.

We studied 28 lung carcinomas representing different histological types and three of their regional lymph node metastases immunohistochemically by using specific antibodies against two basement membrane proteins--the 7S domain of type IV collagen and the P1 fragment of laminin. One feature common to all peripherally growing tumors, regardless of the histologic type, was an intact basement membrane between the tumor and the unaffected lung tissue. At these locations, the basement membrane was organized into alveolar structures that did not differ from normal lung tissue. The fibrotic central areas of the tumors did not exhibit this phenomenon. Based on these findings, we believe that malignant tumors of the lung utilize preserved alveolar basement membranes for their local spread. This finding seems to represent a general property of all lung carcinomas, not only adenocarcinomas of the bronchiolo-alveolar type.

Adenocarcinoma↗
PubMed1990

Simultaneous evaluation of epithelial cell function by CA 125 and stromal cell activity by aminoterminal propeptide of type III procollagen (PIIINP) in ovarian carcinoma.

Serum concentrations of CA 125 and the aminoterminal propeptide of type III procollagen (PIIINP) were measured in 50 patients with clinical stage I or II (N = 16) and stage III or IV (N = 34) ovarian carcinoma before and during cytotoxic chemotherapy. Initially pathological concentrations of CA 125 were found in 92% of all patients and 100% of those in clinical stages II, III and IV. The concentration of PIIINP was at pathological levels in 71% of patients. Serum concentrations of CA 125 (P = 0.04) and PIIINP (P = 0.005) were higher in stages III and IV than in stages I and II. Initial concentration of PIIINP, but not of CA 125, was significantly (P less than or equal to 0.001) higher in the 19 patients who died of the malignancy than in the 31 patients alive at the end of the follow-up period. There was a significant inverse correlation (P = 0.01) between the initial PIIINP values and the survival time among patients with a poor prognosis. Initial concentration of CA 125 was of no prognostic value. During the follow-up, the serum concentrations of CA 125 and PIIINP correlated closely with clinical changes in the disease. Either or both of the tumour markers increased or remained at pathological levels before clinical relapse in patients who had initially responded. PIIINP was a more accurate marker (84%) than CA 125 (63%) in this respect. The information obtained from CA 125 and PIIINP concentrations was identical in 65% and complementary in 33% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

External thoracic duct-venous shunt in conscious pigs for long term studies of connective tissue metabolites in lymph.

An experimental animal model for lymph studies is described. Thoracic duct-venous shunt was established in 12 pigs. Shunt patency averaged 5.5 days. The composition of connective tissue metabolites in lymph and serum were investigated during a standardized surgical operation (thoracotomy) under general anesthesia. We measured the carboxyterminal propeptide of type I procollagen (PICP), the aminoterminal propeptide of type III procollagen (PIIINP) hyaluronan (HA) and total protein. During surgery/anesthesia lymph PICP (p less than 0.04), lymph PIIINP (p less than 0.03) and serum PIIINP (p less than 0.01) and serum PIIINP (p less than 0.03) increased. The changes may be explained by the inactive physical state of the animals. HA showed wide variations, with a tendency like PIIINP. In conscious animals the lymph/serum ratio of PIIINP and HA were 10 and 35, respectively, indicating that lymph is a major route of tissue clearance for these components. The lymph/serum ratio of PICP was 1.0 in conscious pigs, indicating a direct release into the circulation. Total protein in lymph decreased (p less than 0.04) during surgery/anesthesia, whereas no changes were observed in serum. Pigs can be used instead of dogs and sheep in studies on lymph. The effect of surgery/anesthesia must be taken into consideration.

Anastomosis, Surgical↗
PubMed1990

Aminoterminal propeptide of type III procollagen in serum during wound healing in human beings.

The concentration of the aminoterminal propeptide of type III procollagen (PIIINP) in serum as an indicator of tissue repair was studied in 71 surgical patients undergoing minor, moderate abdominal, major abdominal, or hip surgery. An increase in serum PIIINP concentrations took place within the first week, and its magnitude was related to the extent of the soft-tissue operations. After the hip replacement, the maximum PIIINP concentration was reached somewhat later. Very high levels of serum PIIINP were seen in three patients with serious wound infections. The serum PIIINP antigenicity consisted both before and after surgery of equal proportions of two forms, one corresponding to the propeptide as set free during synthesis of new collagen and the other being larger and probably derived from turnover of type III collagen fibers. The proportion of the latter form was accentuated in infection. In contrast, in the wound the form derived from synthesis of type III collagen predominated. These results suggest that the postoperative increase in serum PIIINP levels is partly the result of tissue repair and partly the result of whole-body turnover of type III collagen.

Abdomen↗