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L Risteli

Publications and source records attributed to L Risteli.

At least 127 records · Page 7Linked to original sources
PubMed1992

A new method to measure type I and III collagen synthesis in human skin in vivo: demonstration of decreased collagen synthesis after topical glucocorticoid treatment.

Collagen is synthesized as procollagen and large extra domains known as propeptides are cleaved off enzymatically. In the present study we have measured the carboxyterminal propeptide of type I collagen (PICP) and the aminoterminal propeptide of type III collagen (PIIINP) in blister fluids of human skin. High concentrations of PICP were found in the spontaneous blisters of patients with bullous pemphigoid, erysipelas, or erythema multiforme. Detectable amounts were also found in suction blisters induced on healthy skin. Because the concentrations in suction blisters were several times higher than in corresponding serum, most of PICP and PIIINP was derived from the underlying dermis. This method was used for assessing type I and type III collagen synthesis after topical glucocorticoid treatment. Clobetasol-17-propionate (CP) decreased the concentrations of PICP by 75% after 1 d of treatment, the maximum inhibition (92%) being found after 2 d treatment. PIIINP was also affected. Hydrocortisone and hydrocortisone-17-butyrate also decreased the concentrations of PICP and PIIINP, but less markedly than CP. Partial recovery was seen 3 d after stopping the treatment. Thus measurement of collagen type specific propeptides in suction blisters can be used as an estimate of collagen synthesis in vivo, avoiding both local anesthesia and skin biopsing. With radioimmunoassays for PICP and PIIINP a large number of samples can also be processed simultaneously.

Administration, Topical↗
PubMed1992

Systemic glucocorticoid treatment decreases serum concentrations of carboxyterminal propeptide of type I procollagen and aminoterminal propeptide of type III procollagen.

The effect of systemic glucocorticoid treatment on collagen synthesis in patients with various dermatoses was studied by measuring the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) in serum. Changes in the propeptide concentrations were compared with those of osteocalcin, which reflects osteoblastic activity, and tartrate resistant acid phosphatase (TRAP), which reflects osteoclastic activity. The treatment caused significant decreases in levels of PICP, PIIINP and osteocalcin of 38, 34 and 49%, respectively (P less than 0.001). For TRAP, both increases and decreases were seen. The effects on PICP and PIIINP were evident 2-4 days after the onset of steroid therapy. The decrease in PICP was dose-related (r = 0.470, P less than 0.005) but even relatively small doses (0.1 mg of prednisone/kg/1 day) caused a significant reduction in PICP. After cessation of treatment, the levels of PICP returned to the pretreatment level in 1 week. The present study demonstrates that systemic glucocorticoid therapy in humans suppresses the synthesis of type I and III collagens and also non-collagenous bone matrix proteins.

Acid Phosphatase↗
PubMed1992

Monitoring of multiple myeloma and bone marrow fibrosis with aminoterminal propeptide of type III collagen (PIIINP).

Bone marrow fibrosis is known in myelomatosis and depends on the extent of plasma cell infiltration. The serum concentration of the aminoterminal propeptide of type III procollagen (PIIINP) has previously been reported to reflect fibrogenesis in the marrow in myelofibrosis. Here we followed 15 consecutive patients with newly diagnosed multiple myeloma with repeated PIIINP measurements during treatment with intermittent courses of melphalan and prednisolone. PIIINP was found to change with clinical behaviour of the disease, nonresponders and patients with recurrent disease having elevated values and the values in responders decreasing to the normal level or remaining there. Collagen fibres in plasma cell infiltrates of biopsies from bone marrow or skeletal tumours of these patients stained heavily with antibodies against PIIINP. Our results suggest that PIIINP works as a noninvasive indicator of bone marrow fibrogenesis. In multiple myeloma PIIINP is a sensitive, but not specific marker of disease course.

Adult↗
PubMed1992

Connective tissue response to major surgery and postoperative infection.

Type I and type III collagen are components of a healing wound, and major structural proteins. According to our previous study, wound fluid concentrations of the liberated propeptide extensions of procollagens can be used to monitor collagen synthesis in the wound. Serum concentrations of the carboxyterminal propeptide of type I procollagen (PICP), and the aminoterminal propeptide of type III procollagen (PIIINP) were studied here for up to half a year in 102 patients, admitted for major abdominal surgery. In a frequent follow-up (n = 9), one minimum and two maxima were found for S-PICP, occurring 1 day, 7 days, and 2 months after surgery, respectively. S-PIIINP had a minimum at 1 day and a peak at 10 days. Relative changes (follow-up result/pre-operative concentration) of the propeptides in 50 uncomplicated patients were compared. The 1-day minimum of S-PICP was 0.60 (SD 0.18), and that of S-PIIINP 0.89 (0.27), (P less than 0.0001, 95% CI for the mean difference 0.21 to 0.36). The 7-day peak of S-PICP was 1.4 (0.5), and that of S-PIIINP 2.5 (1.2), (P less than 0.0001, CI 0.81 to 1.42). The 2-month-peak of S-PICP was 1.6 (0.3), and at the same time the relative S-PIIINP was still 1.7 (0.3) without any separate peak. Major infectious (n = 8) and other (12) complications, exploratory procedures (22) and patients with abnormal pre-operative propeptide levels (8) were studied separately. Two early deaths were excluded. Only major infection had a remarkable effect on the responses of S-PICP (3/8) and S-PIIINP (5/8).(ABSTRACT TRUNCATED AT 250 WORDS)

Collagen↗
PubMed1992

Aminoterminal propeptide of type III procollagen in ovarian cancer. A review.

The concentration of the aminoterminal propeptide of type III procollagen (PIIINP) in serum is a measure of the activity of the metabolism of type III collagen, which is a major constituent of soft connective tissues and of the connective tissue stroma of solid tumours. In advanced ovarian carcinoma, serum PIIINP serves as a tumour-associated antigen, its changes reflecting and preceding changes in the clinical behaviour of the malignancy. Elevated values of serum PIIINP are also observed in endometrial and cervical malignancies, though less frequently than in ovarian tumours. Very high concentrations of PIIINP are found in ovarian carcinoma ascites, suggesting an ongoing fibro-proliferative reaction in the peritoneal cavity as a response to the tumour.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1991

Aminoterminal propeptide of type III procollagen in cerebrospinal fluid. Variation with age and in childhood leukemia.

Analyses of the aminoterminal propeptide of type III procollagen (PIIINP) in the cerebrospinal fluid (CSF) of 55 children and five young adults without any structural central nervous system (CNS) lesion are reported. The concentration was age-dependent, in that infants and small children had quite high values, whereas the concentration remained relatively constant after the age of 1.5 years. The concentrations of PIIINP in the CSF of 44 children with acute lymphoblastic leukemia (ALL) were prospectively determined at the time of diagnosis and during treatment, since deposition of type III collagen is known to occur during fibroproliferative responses triggered by inflammation. Chemical arachnoiditis is known to be associated with intrathecal methotrexate therapy in children with leukemia. The mean concentration in these children at diagnosis (5.8 micrograms/l +/- SD 2.8 micrograms/l) did not differ from that in age-matched controls (6.7 micrograms/l +/- SD 3.2 micrograms/l). Depending on type of the disease, the children were treated according to two different protocols. PIIINP concentrations were significantly higher during the therapy phases which included intrathecally administered methotrexate (P less than 0.001) than at diagnosis of the disease. Corticosteroid treatments were always associated with a significant decrease in PIIINP concentrations (P less than 0.01 and P less than 0.001 in the two groups, respectively), irrespective of the therapy phase. The results suggest that an increase in PIIINP concentration in the CSF of children with ALL is an indicator of a fibroproliferative response in the arachnoid. Corticosteroids may repress this response and possibly also prevent the development of adhesions in the arachnoid.

Adolescent↗
PubMed1991

Effect of dextran on synthesis, secretion and deposition of type III procollagen in cultured human fibroblasts.

When subconfluent cultures of primary human skin fibroblasts are incubated for 20 h in the presence of 5% neutral dextran, the newly synthesized procollagens are shifted from the medium into the pericellular matrix fraction. This is accompanied by an overall decrease by 30-50% in the secretion rates of these proteins, as indicated by the incorporation of tritiated proline into collagenase-sensitive macromolecules and by radioimmunoassays for the propeptide regions of type I and III procollagens. Inhibition of tyrosine sulphation in newly formed type III procollagen by NaClO3 does not change the distribution of this protein between the medium and matrix fractions either in the presence or in the absence of the polymer. Processing of type III procollagen at its N-terminus is incomplete in this situation, irrespective of whether the protein is present mainly in the medium or in the pericellular matrix. The concentrations of the mRNAs for the pro alpha 1(I)- and pro alpha 1(III)-chains of procollagens and for actin were monitored for up to 20 h; in the dextran-treated cultures these are not different from the corresponding concentrations in control cultures, indicating that the rapid down-regulation of the synthesis of type I and III procollagens in response to the enhanced pericellular matrix deposition induced by dextran is not due to transcriptional mechanisms.

Blotting, Northern↗
PubMed1991

Effects of a combined estrogen-gestagen regimen on serum levels of the carboxy-terminal propeptide of human type I procollagen in osteoporosis.

Estrogen stimulates osteoblastic collagen production in vitro, but whether the same stimulation takes place in vivo is still unknown. To test the stimulatory effects of a combined estrogen-gestagen regimen in vivo we monitored serum levels of the carboxy-terminal propeptide of human type I procollagen (S-PICP) in a group of 12 osteoporotic women over a 150 week treatment period. Spinal bone mineral content (BMC) increased to a maximum of 5% over pretreatment values around week 90. Serum alkaline phosphatase (S-AP) and serum bone gla protein (S-BGP) both fell from initial values of 220 U/liter and 39 ng/ml, respectively, to 146 U/liter (p less than 0.01) and 27.2 ng/ml (NS) around week 60 and remained reduced over the remaining treatment period. S-PICP also fell from 117 to 68 micrograms/liter at week 60 and 70 micrograms/ml at week 150 (P less than 0.01). This is equal to a reduction to 32 +/- 10% pretreatment levels. The reduction in S-PICP was not significantly different from that of the other two markers of bone formation (S-AP and S-BGP). Thus, provided the metabolic clearance of PICP remains unaltered after hormone replacement therapy, no major stimulation of osteoblastic collagen type I synthesis was demonstrable during estrogen-gestagen treatment in this population of osteoporotic women. The changes in bone markers seen in this study are therefore consistent with an estrogen-mediated reduction in the frequency of remodeling activation. Because of the reduction in bone turnover and methodologic limitations of bone marker assays, however, smaller increases in the amount of bone formed per activation could remain undetectable.

Aged↗
PubMed1991

Use of a marker of collagen formation in osteoporosis studies.

Type I collagen accounts for most of the organic matrix of bones, but it is also an important constituent of soft connective tissue. Assessment of the turnover of such collagen is particularly relevant to bone metabolism. Determination of the carboxyterminal propeptide of type I procollagen (PICP) is a means of estimating the rate of type I collagen synthesis in the body. Serum concentrations of PICP have been shown to correlate with the rate of bone formation.

Adult↗
PubMed1991

The carboxy-terminal propeptide of type I procollagen in serum as a marker of bone formation: the effect of nandrolone decanoate and female sex hormones.

Seventy-nine osteoporotic (prior forearm or vertebral fracture), but otherwise healthy, postmenopausal women (aged 55 to 75 years) were allocated to two double-blind trials: (1) 39 women received either nandrolone decanoate (anabolic steroid) 50 mg as an intramuscular depot injection or a placebo injection every 3 weeks for 1 year; and (2) 40 women received either 2 mg 17 beta-estradiol plus 1 mg norethisterone acetate or placebo tablets daily for 1 year. Sixty-seven (85%) completed the 1 year of treatment. Serum concentration of type I procollagen carboxy-terminal propeptide (PICP) was measured before and at 3, 6, 9, and 12 months of therapy. In addition, 32 of the women had an iliac bone biopsy taken after double tetracycline labeling. Initial serum PICP correlated significantly with histomorphometrically measured rate of bone formation (r = .4; P less than .05) and plasma bone Gla protein (r = .6; P less than .001), but not with histomorphometrically measured bone resorption or biochemical estimates of bone resorption (fasting urinary hydroxyproline and calcium). Estrogen-progestogen therapy significantly decreased (P less than .001) serum PICP by about 30%, whereas anabolic steroid therapy hardly affected it. We conclude that serum PICP may be used as a noninvasive measurement of bone formation on a group basis. Whereas bone formation is clearly decreased during estrogen-progestogen therapy, it is not affected by long-term therapy with anabolic steroids.

Aged↗
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

Formation of osteoblast-like cells from human mononuclear bone marrow cultures.

Osteoblast-like cells are commonly found in the vicinity of osteoclasts formed in long-term human bone marrow cultures, and they are believed to be derived from osteogenic cell precursors belonging to the stromal cell system. This paper describes a new culture method for human osteoblasts from the adherent cell population of long-term human mononuclear bone marrow cultures. The cells obtained exhibited all the classic characteristics of osteoblasts. They contained high intracellular concentrations of alkaline phosphatase and they secreted the osteoblast-specific marker bone Gla protein. Collagen production was mainly (95-98%) procollagen type I propeptide and only minute quantities of procollagen type III propeptide were detectable by radioimmunoassay in the conditioned medium. After eight weeks the cells formed a mineralized matrix on exposure to beta-glycerophosphate and ascorbic acid. This system provides a model for the study of osteoblast differentiation in vitro and may form the basis for the use of defined media in bone cell cultures due to the presence of high concentrations of osteoblast precursors.

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

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↗