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Biomedical subjects

L Risteli

Publications and source records attributed to L Risteli.

At least 19 recordsLinked to original sources
PubMed1995

Immunohistochemical study of type I collagen and type I pN-collagen in benign and malignant ovarian neoplasms.

BACKGROUND: Type I collagen is a major constituent of the interstitial connective tissue. Although ovarian carcinoma is known to induce the expression of type I collagen in the peritoneal cavity, the distribution and metabolic activity of this collagen in ovarian tumor tissue are not known. METHODS: The distributions and staining intensities of different molecular forms of type I collagen in ovarian neoplasms were studied immunohistochemically with antibodies to the aminoterminal propeptide of type I procollagen (PINP) and the cross-linked carboxyterminal telopeptide of type I collagen (ICTP), reflecting the presence of newly synthesized and old, cross-linked type I collagen, respectively. RESULTS: A regular pattern of moderately staining, relatively uniform fibers was observed in the stroma of benign serous and mucinous cystadenomas, indicating limited participation in tumor growth. The staining was accentuated subepithelially in borderline epithelial neoplasms and in well differentiated cystadenocarcinomas, suggesting induction of the stromal collagen synthesis by the tumor cells. Fewer degraded collagen fibers were found in moderately differentiated carcinomas, most likely because of enzymatic degradation of the stroma surrounding the neoplasms during tumor spread. Strongly staining, irregular collagen fibers occurred closely around islets of tumor cells in undifferentiated malignant neoplasms and in metastases of ovarian carcinomas; also, intracellular staining was present in part of the malignant cells. In most cases, the staining reactions obtained with the two different antibodies were similar, probably indicating rapid processing of the newly synthesized type I collagen (indicated by PINP) to a maturely cross-linked form (indicated by ICTP). CONCLUSIONS: Synthetic and degradative processes are typical of the collagenous matrix in malignant ovarian tumors. Aberrant expression of type I collagen may occur in anaplastic ovarian carcinomas.

Adult↗
PubMed1995

Responses of type I and type III collagen synthesis after replacement of the hip joint.

Liberation of the carboxy-terminal propeptide of type I procollagen (PICP) and the amino-terminal propeptide of type III procollagen (PIIINP) into body fluids reflects synthesis of the respective collagen types. Here, we followed PICP and PIIINP in serum with specific radioimmunoassays after hip surgery. Preoperative median of S-PICP was 112 micrograms/liter (range 87 to 154, n = 9), the 1-day median being 58 micrograms/liter (33 to 79). The corresponding medians for S-PIIINP were 4.4 micrograms/liter (3.5 to 7.0) and 3.3 micrograms/liter (2.0 to 3.5). The medians reached their maximums 14 days after surgery, 172 micrograms/liter (122 to 440) for S-PICP and 12.4 micrograms/liter (8.0 to 15.4) for S-PIIINP, after which the preoperative values were slowly approached over several months. Comparable results were found in a greater sample (n = 50). Our results indicate that the synthesis of structural collagen is inhibited immediately after surgery, but the inhibition is soon overcome by active collagen synthesis at the site of trauma. Collagen metabolism remains activated for several months after surgery.

Collagen↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Type I collagen degradation product in serum of patients with early rheumatoid arthritis: relationship to disease activity and radiological progression in a 3-year follow-up.

The new assay of cross-linked carboxyterminal telopeptide of type I collagen (ICTP), a serum marker for bone collagen degradation, was evaluated in serial measurements of 66 patients with early RA during a 3-yr prospective study. Initially 51% of RA patients had elevated levels of serum ICTP compared to healthy controls. During the subsequent months after starting anti-rheumatic treatment, the mean ICTP levels decreased in parallel with the clinical and laboratory variables measuring disease activity. Despite marked clinical improvement with anti-rheumatic treatment, a steady increase in radiological progression of joints was observed. Throughout the follow-up serum ICTP levels correlated with inflammatory parameters and from the first year on with the radiological changes assessed annually. However, initial serum ICTP levels correlated better than the other variables of disease activity with the subsequent erosive progression of joints indicating that measurement of serum ICTP may serve as one of the prognostic markers for joint damage in early RA.

Adult↗
PubMed1994

Systemic glucocorticoids decrease the synthesis of type I and type III collagen in human skin in vivo, whereas isotretinoin treatment has little effect.

The effects of systemic glucocorticoid and isotretinoin treatments on type I and type III collagen synthesis in intact skin were investigated by measuring the carboxyterminal and aminoterminal propeptides of type I procollagen, and the aminoterminal propeptide of type III procollagen, in suction blister fluid (SBF), in a study of 27 patients. All three parameters were significantly lower in the SBF of glucocorticoid-treated patients than in controls or patients undergoing treatment with isotretinoin, whereas the latter two groups did not differ significantly from each other. During glucocorticoid treatment, the concentrations of the procollagen propeptides were only about 20% of the corresponding control values, indicating that systemic therapy with prednisone at a dose of 0.48 mg/kg per day almost totally abolishes collagen synthesis in the skin. These results indicate that systemic glucocorticoid treatment suppresses the synthesis of both type I and type III collagen in the dermis, and suggest that many side-effects of these drugs, such as atrophy of the skin, are due to this inhibition. Systemic isotretinoin treatment did not stimulate skin collagen synthesis. Thus, its regenerative effect on connective tissue may be mediated by mechanisms other than direct stimulation of collagen synthesis.

Adult↗
PubMed1994

Serum ionized calcium, intact PTH and novel markers of bone turnover in bedridden elderly patients.

Chronic immobilization could markedly affect calcium and bone metabolism in elderly people. To investigate this, and to test the theory of 'type II' osteoporosis in bedridden elderly patients with low vitamin D status, 55 such subjects were examined. Serum concentrations of ionized calcium (Ca++), intact parathyrin (PTH) and two novel markers of bone collagen formation (carboxyterminal propeptide of type I procollagen; PICP) and resorption (carboxyterminal crosslinked telopeptide of type I collagen; ICTP) were measured. The effects on these parameters after 40 weeks of supplementation with vitamin D (1000 IU d-1) and/or calcium (1 g d-1) were subsequently prospectively evaluated. Despite low (mean 11.6 nmoll-1) serum 25-hydroxyvitamin D levels (25-OHD), those of 1,25-dihydroxy-vitamin D (1,25-(OH)2D) were mostly normal. Neither correlated with Ca++ or PTH. PTH correlated negatively not only with Ca++ (r = -0.328, P < 0.05) but also with ICTP (r = -0.306, P < 0.05). Mean PICP was normal but ICTP was elevated and tended to correlate positively with Ca++ (r = 0.268, P = 0.06). Vitamin D supplementation did not change PICP or ICTP considerably, despite slightly increased 1,25-(OH)2D and slightly decreased PTH. Ca++ values were normal and remained stable. In conclusion, Ca++ and PTH are poor indicators of vitamin D status in chronically immobilized elderly subjects. Furthermore, the results suggest that the increased bone resorption is not due to 'type II' secondary hyperparathyroidism; rather the resorption is primarily increased. Correction of vitamin D deficiency does not seem to benefit ageing bones unless adequate mechanical loading is provided.

Aged↗
PubMed1994

Modulating influence of barley on the altered metabolism of glucose and of basement membranes in the diabetic rat.

A study was conducted to explore the effects of different sources of dietary carbohydrate on the altered metabolism of basement membrane proteins (type IV collagen and laminin) that occurs in the streptozotocin-diabetic rat. The substitution of barley for sucrose reduced the elevated plasma concentration of 7-S collagen and of laminin P2, peptide fragments that retain antigenicity of the parent proteins. Similar effects were noted in the liver and kidney content of these peptides. It is suggested that the beneficial property of barley is due to its high content of chromium, as has been demonstrated in the study of glucose metabolism.

Animals↗
PubMed1994

Altered collagen expression in human dentin: increased reactivity of type III and presence of type VI in dentinogenesis imperfecta, as revealed by immunoelectron microscopy.

We used transmission immunoelectron microscopy and polyclonal antibodies to study the reactivities of Types III and VI collagen in dentin of normal human permanent and primary teeth and in primary teeth from five patients with dentinogenesis imperfecta (DI) associated with osteogenesis imperfecta and occurring as a single trait. In the normal permanent tooth, reactivity of Type III collagen was occasional and, where present, peritubular. Staining of normal primary teeth was less occasional but still rare, whereas the abnormal dentin stained more uniformly. Atypical, non-striated fibrillar structures that also showed Type III collagen reactivity were observed in dentin of two of the three patients with DI as a single trait. Later, these two patients proved to be first cousins. Unlike antibodies to the N-terminal pro-peptide of Type I pro-collagen, antibodies to the C-terminal telopeptide of Type I collagen, used for comparison stained the affected dentin homogeneously. Reactivity of Type VI collagen, not detected in normal teeth, was seen in the dentin of all abnormal teeth, in association with non-fibrillar delicate material. This study also shows that although readily detectable in dentin affected by DI, Type III collagen is a minor constituent of normal human dentin matrix.

Collagen↗