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J Risteli

Publications and source records attributed to J Risteli.

At least 127 records · Page 7Linked to original sources

Increased collagen synthesis in psoriasis in vivo.

Psoriasis is an inflammatory skin disease of unknown a etiology which also involves changes in dermal elements. Previous in vitro studies have shown an increased collagen synthesis rate in cultured fibroblasts. In this study collagen synthesis was studied in vivo in the uninvolved skin of psoriatic patients using a newly developed method in which collagen propeptides were measured in suction blister fluid. Both type I and type III collagen synthesis rates, as measured in terms of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP), were increased about two-fold in uninvolved psoriatic skin as compared with controls, the mean level of PICP being 870 and 457 micrograms, respectively (P < 0.001), and of PIIINP being 294 and 124 micrograms, respectively (P < 0.01). The increased collagen synthesis rate was also confirmed by in situ hybridization using specific probes. Collagen mRNAs were found to be particularly abundant in psoriatic patients, who also demonstrated a high collagen synthesis rate when assayed by measuring collagen propeptides. The increased rate of collagen synthesis in the uninvolved psoriatic skin seemed not to be related to the severity of the disease or to various treatments such as UVB, PUVA, retinoids or cytostatic drugs, but seemed more likely to be due to the psoriasis itself. Interestingly, skin thickness was not increased in the patients with psoriasis, even though collagen synthesis was markedly elevated, perhaps suggesting that in psoriasis the turnover rate of collagen is enhanced.

Adult↗

Macrophage colony-stimulating factor 1, a clinically useful tumor marker in endometrial adenocarcinoma: comparison with CA 125 and the aminoterminal propeptide of type III procollagen.

OBJECTIVE: We investigated the clinical utility of macrophage colony-stimulating factor 1 versus CA 125 and the aminoterminal propeptide of type III procollagen in endometrial carcinoma. STUDY DESIGN: Serum levels of the three substances were measured in 159 patients with untreated endometrial adenocarcinoma and in 24 patients treated with cytotoxic chemotherapy for recurrent endometrial adenocarcinoma. RESULTS: Initial concentrations of colony-stimulating factor 1, CA 125, and the aminoterminal peptide of type III procollagen were above the normal range in 73%, 11%, and 27%, respectively, of the patients. Colony-stimulating factor 1 levels correlated with those of the aminoterminal peptide of type III procollagen (r = 0.3, p = 0.002) and CA 125 (r = 0.20, p = 0.036) in the total group and with those of the aminoterminal peptide of type III procollagen in stage I and II patients (r = 0.3, p = 0.0023). Colony-stimulating factor 1 levels correlated significantly with tumor grade, whereas those of CA 125 and the aminoterminal peptide of type III procollagen correlated more closely with clinical stage. Mean colony-stimulating factor 1 levels (9.6 vs 7.7 ng/ml, p = 0.04) and the frequency of elevated CA 125 levels (31% vs 8%, p = 0.048) were higher in patients with poor prognosis than in those with good prognosis. Colony-stimulating factor 1, the aminoterminal peptide of type III procollagen, and CA 125 levels were useful in monitoring clinical behavior of the disease in 88%, 79%, and 63% of the cases, respectively. Levels of all three markers rose with disease progression, whereas colony-stimulating factor 1 and the aminoterminal peptide of type III procollagen fell with clinical responses to therapy. CONCLUSION: Elevated serum colony-stimulating factor 1 levels were the most accurate indicator of the presence and activity (progression, stabilization, or regression) of primary or recurrent disease. Accuracy was not further enhanced by measurement of CA 125 or the aminoterminal peptide of type III procollagen levels.

Adenocarcinoma↗

Type I collagen degradation product (ICTP) gives information about the nature of bone metastases and has prognostic value in prostate cancer.

Although osteosclerotic bone metastases are characteristic of prostate cancer, mixed metastases with a lytic component are not uncommon. Type I collagen is synthesised by osteoblasts and accounts for about 90% of the organic matrix of bone. We have used new specific immunoassays for PICP (carboxy-terminal propeptide of type I procollagen) and ICTP (cross-linked carboxy-terminal telopeptide of type I collagen) which allow simultaneous assessment of the synthesis and degradation of type I collagen respectively. Forty patients with bone metastases due to prostate cancer at the time of diagnosis were investigated with these methods. Twenty-three of them had sclerotic (S) and 17 had mixed metastases with sclerotic and lytic components (S + L) as assessed by radiographs. The concentrations of PICP and ICTP in serum as well as the activity of alkaline phosphatase (AP) were increased in all patients of the S + L group, who had more aggressive bone disease and a shorter survival than the S group (P < 0.017). The ICTP level was above the reference range in half of the patients in the S group, whereas the PICP and AP levels were elevated in 35%. Of the bone markers, only ICTP was of prognostic significance (P < .05). We conclude that ICTP and PICP give information about the type and activity of the skeletal metastases. In addition, ICTP predicts prognosis.

Aged↗

Topical mometasone furoate and betamethasone-17-valerate decrease collagen synthesis to a similar extent in human skin in vivo.

Topical corticosteroids are used extensively to treat inflammatory skin diseases. Long-term use, however, may be associated with adverse effects such as skin atrophy. New steroids have been developed with the objective of increasing efficacy and reducing the incidence of adverse effects. Mometasone furoate (MMF) is one of these new derivatives. The aim of our study was to compare the effects of MMF and betamethasone-17-valerate (BM-17-valerate) on collagen synthesis in human skin in vivo. Fifteen healthy male volunteers applied MMF, BM-17-valerate and vehicle for 1 week to different areas of abdominal skin. Suction blisters were raised on these areas, and a control site, and procollagen propeptide (PICP, PINP, PIIINP) levels in the suction blister fluid were measured by radioimmunoassay. Skin thickness was measured ultrasonically by Dermascan A at the end of the treatment period. The levels of the three propeptides in suction blister fluid were reduced to similar extent by MMF and BM-17-valerate. The 1-week treatment period had no detectable influence on skin thickness. We conclude that MMF and BM-17-valerate decrease collagen synthesis to the same extent in human skin in vivo.

Administration, Topical↗

The effect of topical oestradiol on skin collagen of postmenopausal women.

OBJECTIVE: To examine the effect of topical oestradiol on skin collagen and elastin. SUBJECTS: Twelve postmenopausal women, aged 52 to 76 years. INTERVENTIONS: Topical oestradiol treatment on the skin of lower abdomen and the vehicle only on the contralateral site; once a day for three months. MAIN OUTCOME MEASURES: The content of skin hydroxyproline; the levels of the carboxyterminal propeptide of human type I procollagen (PICP) and of the aminoterminal propeptide of human type III procollagen (PIIINP). The number and the quality of collagen and elastic microfibrils. RESULTS: The amount of hydroxyproline in the skin significantly (P = 0.012) increased from 11.8 to 16.3 micrograms (38%) during oestradiol treatment. After treatment, the PICP level in the blister fluid was significantly (P = 0.024) higher on the treated site than on the control site. Also the level of PIIINP increased, but the change was not statistically significant. Electron microscopy showed morphologic improvement of elastic and collagen fibres, while the number of oxytalan and elaunin fibres was unchanged in light microscopy. CONCLUSIONS: Topical oestradiol treatment increases the amount of skin collagen. The increase in the level of PICP and PIIINP in skin blister fluid indicates that oestradiol treatment stimulates collagen synthesis. Furthermore, our results show that topical ostradiol treatment has a greater influence on the amount than on the quality of skin collagen. On the contrary, in elastic tissue the oestradiol treatment will only result in morphologic improvement.

Administration, Topical↗

Application of markers of collagen metabolism in serum and synovial fluid for assessment of disease process in patients with rheumatoid arthritis.

OBJECTIVE: To assess the potential of markers of collagen metabolism to reflect disease processes in rheumatoid arthritis (RA). METHODS: Serum (S) and synovial fluid (SF) from 59 patients with RA, and a knee joint effusion and serum from 90 control subjects were studied with radioimmunoassays for the aminoterminal propeptides of type I and type III procollagens (PINP and PIIINP, respectively). The breakdown of type I collagen was quantified with a radioimmunoassay for the cross linked carboxyterminal telopeptide of type I collagen (ICTP). RESULTS: About 50% of the patients had increased S-ICTP and S-PIIINP values, whereas S-PINP was increased in only 20% of the patients. The mean SF:S ratios of these markers varied between 4 (for ICTP) and 340 (for PIIINP), indicating that markers of collagen metabolism are formed locally and then released into the circulation. SF-PINP and SF-PIIINP correlated with each other (rs = 0.86, p < 0.001) and with SF-ICTP (rs = 0.69, p < 0.001, and rs = 0.65, p < 0.001, respectively). SF-ICTP was clearly related to radiographic findings in the corresponding knee joint, patients with gross bone deformation having the greatest SF-ICTP concentrations. S-ICTP and S-PIIINP also correlated with conventional markers of disease activity, such as C reactive protein and joint swelling score. CONCLUSION: Markers of collagen metabolism both in serum and synovial fluid can be measured to provide an assessment of disease process in patients with RA. ICTP and PIIINP are the most informative.

Adult↗

Prognostic value of serum hyaluronic acid and type I and III procollagen propeptides in extrahepatic biliary atresia.

Although portoenterostomy has greatly improved the prognosis of extrahepatic biliary atresia (EHBA), 10-20% of patients still die before 5 y of age, and the only treatment option is liver transplantation (LT). To investigate whether these patients may be identified at an early stage, when the changes of successful LT are optimal, we have measured serum concentrations of hyaluronic acid (HA), the amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy-terminal and amino-terminal propeptides of type I procollagen (PICP, PINP) in 24 selected patients with EHBA, both before portoenterostomy and then every 6 mo until death (n = 10, age at death = 7-20 mo), LT (n = 6, age at LT = 1.1-4.8 y) or 5 y of age (n = 8). Raised serum HA above 200 micrograms/L before portoenterostomy identified those patients who would die or require LT in the first 5 y of life with a positive predictive value of 88%; after portoenterostomy, longitudinal changes in HA reflected clinical status in each patient. None of the other three markers was of prognostic value, and only PIIINP showed any relationship with clinical status, and then only up to 1.5 y. Interestingly, PINP (but not PICP) tended to be low in all patients before portoenterostomy and may reflect impaired bone collagen metabolism during early skeletal changes in EHBA. This study therefore suggests that measurement of serum HA may be a useful complementary test in EHBA, particularly in identifying, at an early stage, those patients who should be considered for LT.

Age Factors↗

Comparison of the effect of hydrocortisone, hydrocortisone-17-butyrate and betamethasone on collagen synthesis in human skin in vivo.

It has been shown previously that topical corticosteroid treatment decreases collagen synthesis in human skin in vivo and that the adverse effects are due to reduced collagen synthesis. The aim of the present study was to evaluate the effect of hydrocortisone, hydrocortisone-17-butyrate and betamethasone on collagen synthesis in human skin in vivo. Fourteen healthy male volunteers applied hydrocortisone, hydrocortisone-17-butyrate, betamethasone and vehicle twice a day for one week to four separate areas marked on their abdominal skin. The collagen synthesis rate in the skin was measured by assaying collagen propeptides from the suction blisters induced on the treated areas. Aminoterminal propeptide of type I procollagen (PINP) and aminoterminal propeptide of type III procollagen (PIIINP) were measured from skin blister fluid using radioimmunoassays. Skin thickness was measured with ultrasound. Hydrocortisone decreased the two propeptides studied in the suction blister fluids less than did hydrocortisone-17-butyrate and betamethasone, but the interindividual variation was great. Hydrocortisone-17-butyrate and betamethasone had almost similar decreasing effects on the propeptides in the suction blister fluid. Hydrocortisone decreased the concentrations of PINP and PIIINP by about 35%. In some subjects (4/14) the decline of the collagen propeptide levels was over 50%. The decline in the concentration of PINP was 63% by hydrocortisone-17-butyrate and 69% by betamethasone, while the decrease in PIIINP was 55% by hydrocortisone-17-butyrate and 62% by betamethasone. None of the treatments had any effect on skin thickness within one week. In conclusion, it seems that hydrocortisone is less atrophogenic than hydrocortisone-17-butyrate and betamethasone, as shown by radioimmunoassays for collagen propeptides. The order of inhibitory potency of the three glucocorticoids on collagen synthesis was hydrocortisone < hydrocortisone-17-butyrate < betamethasone. Thus, assay of collagen propeptides from suction blisters can be used to screen various steroids with respect to their action on collagen synthesis.

Administration, Topical↗

Elevated serum ICTP concentrations reflect poor prognosis in patients with ovarian carcinoma.

The effect of ovarian carcinoma on the circulating concentration of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) was studied in 17 patients before and during treatment. ICTP is a complex peptide released from type I collagen, which is the main organic component of bone matrix but also induced in ovarian carcinoma tissue and the peritoneal cavity by the tumour. CA 125 and the aminoterminal propeptide of type III procollagen (PIIINP) were also measured. The preoperative CA 125, PIIINP and ICTP concentrations were pathological in 16 (94%), nine (53%) and seven (41%) patients, respectively. There was a positive correlation between the PIIINP and ICTP levels in serum. After surgery and one course of cytotoxic chemotherapy, the median CA 125 concentration decreased whereas those of PIIINP and ICTP increased. During monitoring of the treatment response, patients with regressive disease showed lower CA 125 concentrations than those with stable or progressive disease. For PIIINP and ICTP there was no clear difference between these response categories, but altogether, simultaneously increasing serum CA 125, PIIINP and ICTP concentrations were consistently associated with poor prognosis.

Adult↗

Clearance of NH2-terminal propeptides of types I and III procollagen is a physiological function of the scavenger receptor in liver endothelial cells.

This study was undertaken to determine the fate of circulating NH2-terminal propeptide of type I procollagen (PINP) in rats. Radiolabeled PINP showed a biphasic serum decay curve after intravenous injection. 79% of the material disappeared from the blood during the initial alpha-phase (t1/2 alpha = 0.6 min), while the remaining 21% was eliminated with a t1/2 beta of 3.3 min. The major site of uptake was the liver, 78, 1, and 21% of its radioactivity being recovered in isolated liver endothelial cells (LEC), Kupffer cells, and parenchymal cells, respectively. In LEC, fluorescently labeled PINP accumulated in small (0.1 microns) peripheral and larger (> 0.1 microns) perinuclear vesicles within 10 min at 37 degrees C after a binding pulse at 4 degrees C. These grew in size with increasing chasing time, reaching a maximum diameter of 1 microns or more after 30 min, and taking the shape of rings that were stained only along their periphery. At chase intervals exceeding 30 min, the size of the vesicles decreased, and after 60 min the stain appeared in smaller, densely stained perinuclearly located vesicles. Degradation of 125I-PINP to free smaller fragments and 125I- was significant after 30 min. Only formaldehyde-treated albumin, acetylated LDL, polyinosinic acid and NH2-terminal propeptide of type III procollagen (PIIINP) competed with PINP for uptake. These findings indicate that clearance of PINP and PIIINP, which are normal waste products generated in large quantities, is a physiological function of the scavenger receptor in LEC.

Animals↗

Effect of the menopause and hormone replacement therapy on the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen.

We investigated the effect of the menopause and postmenopausal hormone replacement therapy (HRT) on the serum concentration of carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), a potential new biochemical marker of bone resorption. A group of 44 healthy postmenopausal women, aged 45-54 years, had about 19% higher serum ICTP than did a group of 42 healthy premenopausal women aged 35-50 years (3.6 +/- 0.8 micrograms/l v 3.0 +/- 0.7 micrograms/l (mean +/- SD); p < 0.01), although there was a large overlap in the values. The 44 postmenopausal women also participated in a longitudinal clinical study, in which 20 received HRT and 24 received a placebo. Compared with the placebo group, those who received HRT had a significant (p < 0.05) decrease in ICTP of about 12% at the end of 1 year of treatment, but again there was considerable overlap in the values. The menopause- and HRT-induced changes in ICTP were less than those seen in serum osteocalcin, serum total alkaline phosphatase, and fasting urinary excretion of hydroxyproline, calcium, pyridinoline and deoxypyridinoline. We conclude that the menopause increases and HRT decreases ICTP, although these changes are less pronounced than those seen in other biochemical markers of bone turnover.

Animals↗

Differential processing of type I and type III procollagens in the tumour cysts and peritoneal ascitic fluid of patients with benign and malignant ovarian tumours.

Progressive ovarian carcinoma induces the synthesis of type I and type III procollagens both in the tumour tissue and in the peritoneal cavity. We studied the processing of these proteins by determining the different antigen forms related to their propeptide parts by gel filtration and subsequent immunological assays. Samples of ovarian cyst fluid and peritoneal ascitic fluid were obtained from patients with benign and malignant ovarian tumours. In both benign and malignant ovarian cysts, the predominant procollagen antigens were the free propeptides, with few or no larger components, indicating efficient processing of types I and III procollagens in the tumour tissue. In ascitic fluid the processing was more variable. The aminoterminus of type III procollagen was partially unprocessed in all samples studied, whereas that of type I procollagen was nearly always completely processed. There was a clear difference between malignant and benign tumours in the processing of the carboxyterminus of type I procollagen: a significant part of the carboxyterminal propeptide antigen was invariably associated with a collagenous domain in malignant tumours, whereas in benign tumours the free propeptide predominanted. The results indicate that interstitial procollagens are effectively processed in the tumour tissue during the fibroproliferative reaction typical of malignant ovarian tumours, whereas the processing of the procollagens released into peritoneal ascitic fluid is incomplete.

Ascitic Fluid↗

Assessment of bone remodeling using biochemical indicators of type I collagen synthesis and degradation: relation to calcium kinetics.

In this study, we investigated the relation between calcium kinetic indices of bone remodeling (resorption rate, r; and formation rate, m, respectively) and two serum markers of type I collagen turnover: the pyridinoline cross-linked carboxyterminal telopeptide domains of type I collagen (S-ICTP a marker of bone matrix degradation) and the carboxyterminal propeptide of human type I procollagen (S-PICP, a marker of bone matrix formation). We studied three groups: (i) healthy controls (n = 19), (ii) a mixed group of high and low-turnover bone diseases without mineralization defects (myxedema, thyrotoxicosis and primary hyperparathyroidism n = 38), and (iii) osteoporosis (n = 52). In healthy controls, a significant regression of S-PICP on m was obtained (R = 0.53, SEE/Y = 0.44, P < 0.02). Significant regressions were also demonstrable in high- and low-turnover bone disease (R = 0.50, P < 0.001), SEE/Y = 61%) and osteoporosis (R = 0.49, P < 0.001, SEE/Y = 50%). In controls the regression coefficient for the regression of S-ICTP on r was 0.19 (NS), in high and low turnover bone disease 0.66, (SEE/Y = 59%, P < 0.001) and in the osteoporotic group 0.40 (SEE/Y = 61%, P < 0.01). We conclude that S-PICP and S-ICTP reflect whole skeletal bone formation and resorption rates in a variety of metabolic bone diseases including osteoporosis.

Adolescent↗

Pachydermoperiostosis: analysis of the connective tissue abnormality in one family.

BACKGROUND: Pachydermoperiostosis (PDP) is a rare hereditary disease characterized by hyperostosis, clubbing of fingers, coarse skin, and abnormalities in other organs, such as the gastrointestinal tract. Previous studies have disclosed several abnormalities in the connective tissue in these patients. OBJECTIVE: The purpose of the study was to investigate connective tissue abnormalities in one family with PDP. METHODS: Clinical features were evaluated; x-ray, immunohistochemical, and electronmicroscopic studies were performed; and markers of collagen metabolism and lysosomal enzymes were determined. RESULTS: Immunohistochemical and ultrastructural studies revealed accumulation of tenascin, glycosaminoglycans, and fibrillar material in apparently disorganized microfibrils of elastic fibers. Osteocalcin levels in the serum were increased, but synthesis and degradation markers of collagen in the serum were not altered. No evidence of a lysosomal enzyme deficiency was found. CONCLUSION: Acidic mucopolysaccharides and some fibrillar material accumulate in the dermis of patients with PDP. Increased levels of osteocalcin in serum indicate higher osteoblastic activity. Markers of synthesis and degradation of collagen were not altered.

Acid Phosphatase↗

Serum type I procollagen peptide: a non-invasive index of bone formation in patients on haemodialysis?

The value of serum procollagen peptide (PICP) as a non-invasive index of bone formation was studied in 18 patients established on haemodialysis. There was a significant correlation between PICP and serum alkaline phosphatase activity (ALP; r = 0.55, P < 0.05), and between PICP and osteocalcin (r = 0.53, P < 0.05). PICP also correlated significantly with histomorphometric indices of bone formation, particularly bone formation rates (BFR) as estimated by the tetracycline double-labelled technique (r = 0.74, P < 0.01), but not with those of bone resorption. There was a similar relationship between BFR and ALP. From the regression analyses, a normal BFR was associated with normal PICP values despite the absence of renal function, suggesting that the impact of renal function on serum concentrations of PICP may not be large. Seven patients had histochemical evidence for significant aluminum overload. In these patients the expected suppression in biochemical and histological indices of bone formation was associated with inappropriately raised PICP concentrations. The mechanism of this discrepancy is not clear, but caution is advocated in the interpretation of PICP in the presence of significant aluminium overload. Our findings otherwise suggest that PICP may be a useful non-invasive index of bone formation in patients on haemodialysis.

Adolescent↗