Biomedical subjects

J Risteli

Publications and source records attributed to J Risteli.

At least 145 records · Page 8Linked to original sources

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

A simple method for predicting bone fractures in PBC patients after liver transplantation.

We introduce a simple serum test to predict which patients will have bone problems after liver transplantation. The crosslinked part of collagen I (s-ICTP) was measured in 21 patients with primary biliary cirrhosis before transplantation. Those with postoperative fractures had increased pretransplant values of s-ICTP compared with those without fractures.

Biomarkers↗

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↗

PubMed1994

Genetic influences on type I collagen synthesis and degradation: further evidence for genetic regulation of bone turnover.

Circulating osteocalcin, a marker of bone formation, is under strong genetic influence, and this effect is related to the genetic influence on bone density. To examine genetic influences on bone turnover further, other markers of bone formation (serum carboxyterminal propeptide of type I procollagen, PICP), bone resorption (serum pyridinoline cross-linked carboxyterminal telopeptide of type I collagen, ICTP), and nonosseous connective tissue synthesis (serum aminoterminal propeptide of type III procollagen, PIIINP) were studied in 82 female twin pairs: 42 monozygotic (MZ) and 40 dizygotic (DZ) twin pairs (mean age, MZ; 48.4 yr; DZ; 45.6 yr). The intraclass correlation coefficients of MZ twin pairs, rMZ, for serum PICP (0.78) and serum ICTP (0.68) were significantly greater than the corresponding rDZ (0.31 and 0.36, respectively), but a genetic effect on serum PIIINP was not demonstrable. Within DZ twin pair differences in serum PICP predicted differences in lumbar spine bone density (r = -0.37); higher serum PICP levels indicating the twin with the lower lumbar spine bone density. Also within pair differences in serum ICTP and PICP predicted differences in bone density at the lumbar spine independent of serum osteocalcin. These data indicate that both synthesis and degradation of type I collagen are genetically determined and that this phenomenon is related to the genetic regulation of bone density.

Analysis of Variance↗

PubMed1994

Increased type I collagen degradation in early rheumatoid arthritis.

OBJECTIVE: To evaluate the serum concentration of the mature, crosslinked carboxy terminal telopeptide of type I collagen (ICTP) in patients with early onset rheumatoid arthritis (RA) and to assess its correlation with clinically relevant features of the disease. METHODS: The serum ICTP concentration was measured in 99 adult patients with RA with a duration of disease less than one year. The main clinical outcome measures were joint count, modified Lansbury index, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Larsen index and number of erosions in peripheral joints. RESULTS: There was a strong positive correlation (p < 0.001) between the serum ICTP concentration and the Lansbury joint index and a weaker but still significant correlation (p < 0.01) between the serum ICTP concentration and the number of eroded hand and foot joints. CONCLUSION: Serum ICTP may have value as a marker of tissue destruction in patients with early RA.

Adolescent↗

PubMed1994

Collagen synthesis in human skin in vivo: modulation by aging, ultraviolet B irradiation and localization.

The effect of aging, sex, skin location and a short whole body ultraviolet B (UVB) phototherapy on type I and type III skin collagen synthesis were studied by measuring carboxy- and aminoterminal propeptides of type I and aminoterminal propeptide of type III procollagens (PICP, PINP and PIIINP, respectively) in suction blister fluid (SBF). The concentrations of PICP and PIIINP correlated negatively with age in the material of 30 men and 27 women (age range 23-86 years, mean age 51 years). As the subjects were divided into 3 age groups (23-34, 35-54 and 55-86 years) and the mean concentrations of the procollagens were compared between the groups, the youngest age groups in men and in the whole material had significantly higher concentrations than the two older age groups. These results confirm the previous results, which have shown by other methods that skin collagen synthesis decreases during aging. SBF was also obtained from 4 different body regions (back, arm, abdomen and leg) of 5 young male subjects and from 2 different body regions (abdomen and thigh) of 9 older subjects. Wide individual range in the concentrations of PICP, PINP and PIIINP was noticed but, in general, none of the body regions seemed to have more excessive collagen synthesis than the other ones. SBF was further collected from abdominal skin of 8 young male dermatological patients receiving UVB phototherapy. When the concentrations of PICP and PIIINP in SBF obtained before the treatment, after the treatment and from the covered control area were compared no statistical differences were noted, suggesting that short UVB treatment has no effect on skin collagen synthesis in vivo.

Abdomen↗

PubMed1994

Familial high serum concentrations of the carboxyl-terminal propeptide of type I procollagen.

We describe a family with an apparently autosomal-dominant trait that caused extremely high circulating concentrations of the carboxyl-terminal propeptide of type I procollagen (PICP). All family members examined had normal values for other biochemical markers of bone formation and degradation and no related clinical abnormalities. Furthermore, their serum concentrations of the amino-terminal propeptide of type I procollagen (PINP) were normal. Although PINP and PICP are released from the same precursor molecule, PINP is cleared from the circulation via the scavenger receptor in liver endothelial cells, whereas PICP is cleared via the mannose receptor of these cells. We thus hypothesize that the clearance of circulating PICP is compromised in the affected subjects of this family, the result of either a defective mannose receptor function or an abnormal molecular structure of their PICP.

Adolescent↗

PubMed1993

Progressive ovarian carcinoma induces synthesis of type I and type III procollagens in the tumor tissue and peritoneal cavity.

Increased serum concentrations of aminoterminal propeptide of type III procollagen occur in advanced ovarian cancer. To study their origin, we compared the expressions of type I and type III procollagens in ovarian tumor tissue and the peritoneal cavity with immunoassays for the propeptide domains of these procollagens. Samples of tumor cyst fluid, peritoneal ascitic fluid, tumor vein blood, and peripheral blood were obtained at operation from 50 women with malignant ovarian neoplasms and 61 women with benign neoplasms. The ascitic fluid concentrations of both type I and type III procollagen antigens were significantly higher in the malignant tumors than in the benign ones, but this difference was evident only for type I procollagen in the tumor cysts. The aminoterminal propeptide of type III procollagen concentration in the peripheral blood was higher in the patients with malignant tumors, whereas the concentrations were similar in the tumor veins. The enhanced type I procollagen synthesis in the malignant tumors did not affect the corresponding antigen in the blood. The findings suggest that progressive ovarian carcinoma invariably induces a fibroproliferative response, characterized by active expression of type I and type III procollagens. The increased circulating aminoterminal propeptide of type III procollagen is derived from the peritoneal cavity rather than from the tumor tissue via the ovarian vein.

Adult↗

PubMed1993

Organization of type III collagen in benign and malignant ovarian tumors. An immunohistochemical study.

BACKGROUND: Abnormal interaction with the extracellular matrix is a basic property of malignant cells. Type III collagen is a major constituent of the extracellular matrix of soft tissues. METHODS: Deposition of the aminoterminal propeptide of type III procollagen (PIIINP) was studied in benign (n = 41), borderline (n = 4), and malignant (n = 32) human ovarian tumors using the avidin-biotin-immunoperoxidase technique and affinity-purified antibodies to human PIIINP: It was then compared with the serum PIIINP concentrations of the patients at the time of operation. RESULTS: In malignant tumors, the distribution of PIIINP was irregular both close to the epithelial cancer cells and further away, in the stroma. Another feature typical of malignant tumors was the varying staining intensity of the PIIINP-positive fibers. The benign tumors were characterized by a regular organization and an intensive staining of PIIINP: Borderline tumors showed a slightly decreased staining intensity and altered PIIINP distribution. A significant positive correlation was found between the PIIINP concentration in serum and the degree of irregularity in the distribution of PIIINP: CONCLUSIONS: These preliminary results indicate that malignant transformation in ovarian tumors is associated with disintegration of adjacent collagenous structures and with alterations in type III procollagen metabolism, which also leads to increased serum PIIINP levels. They suggest that biochemical or immunohistochemical detection of the PIIINP antigen could be clinically useful in ovarian tumors.

Adult↗

PubMed1993

Monitoring of veno-occlusive disease after bone marrow transplantation by serum aminopropeptide of type III procollagen.

Differential diagnosis of hepatic complications after bone marrow transplantation (BMT) is often difficult. To assess whether serum concentrations of the aminopropeptide of type III procollagen (PIIINP) could facilitate diagnosis, we measured serum PIIINP, corrected for age by conversion to standard deviation scores (SDS), serially after BMT in 27 children. A preliminary study of 11 patients showed that a PNIIINP-SDS cutoff of 8.0 was an optimum for diagnosis of veno-occlusive disease (VOD). PIIINP-SDS was increased above cut-off 1-25 days before the onset of clinical signs in the 12 patients (4 from the preliminary group, the others from a group of 16 studied prospectively) who developed VOD, with subsequent changes in PIIINP-SDS mirroring the course of VOD. By contrast, PIIINP-SDS remained below cut-off in all other patients, including 7 with liver graft-versus-host disease and 3 with drug hepatotoxicity. PIIINP-SDS values greater than 8.0 predict, diagnose, and monitor VOD after BMT.

Bone Marrow Transplantation↗

PubMed1993

Serum markers of type I collagen formation and degradation in metabolic bone disease: correlation with bone histomorphometry.

Type I collagen makes up more than 90% of bone matrix. Therefore, analysis of antigens related to collagen formation and degradation in bone should provide good and specific estimates of both bone resorption and bone formation rates. In this study we measured serum levels of the pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) as a marker of bone resorption and serum carboxy-terminal propeptide of type I procollagen (PICP) as a marker of bone formation. Serum levels of the two antigens were correlated to histomorphometric indices of bone resorption and bone formation calculated from iliac crest bone biopsies in a group of 18 individuals with high- and low-turnover bone disease (myxedema, primary hyperparathyroidism, and thyrotoxicosis). After logarithmic transformation the regression of S-ICTP on volume-referent resorption rate (BRs/R/BV) was significant (r = 0.61, p < 0.01, SEM/Y = 56%). S-ICTP also showed a significant regression on the volume-referent cancellous bone balance (r = -0.45, p < 0.05, SEM/Y = 412%). S-PICP was significantly correlated to the mineral appositional rate (r = 0.53, p < 0.05) and volume-referent bone formation rate (r = 0.61, p < 0.01, SEM/Y = 48%). The correlation to bone turnover as expressed in the activation frequency was also highly significant (r = 0.61, p < 0.01, SEM/Y = 51%). No significant correlation with wall thickness or bone balance was demonstrable per remodeling cycle. Thus, assays employing antigens that reflect collagen formation and degradation are useful instruments for the evaluation of rates of bone remodeling in metabolic bone disease.

Adult↗

PubMed1993

Procollagen synthesis and extracellular matrix deposition in MG-63 osteosarcoma cells.

We compared the procollagen synthetic properties of MG-63 osteosarcoma cells with those of cultured human skin fibroblasts. In both cells, the expressions of type I and III procollagens are largely dependent on the constant presence of ascorbate and coordinately decreased by the neutral polymer dextran T-40. The amino-terminal propeptides of pro-alpha 1 and pro-alpha 2 chains of type I procollagen are phosphorylated and those of the pro-alpha 1 and pN-alpha 1 chains of type III procollagen both phosphorylated and sulfated, there being no difference in net charge in the propeptides between these cell types. The major differences between MG-63 and normal fibroblasts are the exceptionally high relative synthesis of type III procollagen by MG-63 cells, up to about 40% of the total of types I and III (6% in cultured skin fibroblasts), and the inability of ascorbate-supplemented MG-63 cells to deposit collagens into an insoluble pericellular matrix. A longer dextran treatment shifts up to one-fourth of the proline-labeled extracellular macromolecules into the matrix fraction within 4 days (in control 4%). Despite processing of the procollagens to the respective collagens in the matrix, neither control matrices nor those induced by dextran induced increased production of alkaline phosphatase. In cultures up to 4 days postconfluence the proportion of type III collagen produced tended to increase over that in early confluent cultures. With respect to collagen production, the MG-63 cell line is not a representative of the osteoblast lineage but rather resembles a proliferative wound fibroblast.

Ascorbic Acid↗

PubMed1993

Serum markers of collagen synthesis and degradation in skin diseases. Altered levels in diseases with systemic manifestation and during systemic glucocorticoid treatment.

Serum concentrations of the markers of collagen synthesis and degradation, collagen I propeptide (PICP), collagen III propeptide (PIIINP) and the cross-linked telopeptide of type I collagen (ICTP) were measured in young male dermatological patients and in control subjects. No significant differences were noted between patients suffering from atopic eczema (n = 24), other eczemas (n = 11), acne (n = 8), psoriasis (n = 7) or tinea (n = 9) and the control subjects (n = 24). In the total study population representing patients with common skin diseases and control subjects there was a significant correlation between the serum concentrations of PICP and PIIINP and between the concentrations of PICP and ICTP. This suggests that synthesis of type I and III collagens in vivo is coordinated and that the degradation and synthesis of type I collagen is balanced. These markers were also measured in older patients suffering from psoriasis, eczema and various connective tissue diseases. It was noted that the degree of skin involvement in these diseases was not related to the serum concentrations of the markers of collagen metabolism. The highest levels of PICP and PIIINP were observed in a patient with systemic mastocytosis (PICP 309 micrograms/l and PIIINP 8.0 micrograms/l). Increased levels of PIIINP were also found in patients with a high alcohol consumption. We have previously demonstrated that systemic glucocorticoids reduce collagen propeptide levels in serum. In the present study we also proved that systemic glucocorticoids have no effect on collagen degradation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Impact of chemotherapy on collagen metabolism: a study of serum PIIINP (aminoterminal propeptide of type III procollagen) in advanced sarcomas.

We have previously shown that the serum aminoterminal propeptide of type III procollagen (PIIINP) is a prognostic factor for survival in localised soft-tissue sarcomas, and that elevated values are frequent in metastatic disease. In the present study PIINP is analysed during chemotherapy in 26 patients with advanced sarcomas. Non-responders had a significantly higher pretreatment level of PIIINP than responders (P = 0.05), when only patients with no recent therapeutic interventions were studied. However, during chemotherapy PIIINP followed the clinical course of the malignant disease in only a minority of patients. Patients with recent surgery or recently completed chemotherapy had an increased pretreatment PIIINP value (P = 0.03). In these patients PIIINP declined during chemotherapy irrespective of tumour response. A pretreatment PIIINP level within the reference range tended to increase with time irrespective of response. Moreover, the values taken during a chemotherapy infusion were significantly higher than those immediately preceding the corresponding cycle (P = 0.001). Our results suggest that pretreatment PIIINP is of value as a prognostic factor for chemotherapy response in patients with advanced sarcomas. During chemotherapy PIIINP is of minor importance in monitoring response because of the influence of chemotherapy and other therapeutic interventions on the level of PIIINP.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

Evaluation of the effect of oral clodronate on skeletal metastases with type 1 collagen metabolites. A controlled trial of the Finnish Prostate Cancer Group.

Clodronate relieves bone pain in patients with skeletal metastases. Since the pain relieving mechanism of clodronate may be associated with the antiosteoclastic activity, we have investigated whether the drug has simultaneous actions on bone resorption and pain. Although osteosclerotic metastases are characteristic of prostate carcinoma, bone resorption is also accelerated. The resorbing process can be investigated using a specific immunoassay for ICTP (cross-linked carboxyterminal telopeptide region of type I collagen) which allows the measurement of the degradation of type I collagen in serum samples. We have also determined serum concentration of PICP (carboxyterminal propeptide of type I procollagen) which reflects the synthesis of type I collagen (osteoid). Patients who have relapsed after first-line hormonal therapy, were randomised to receive estramustine phosphate (E) with or without clodronate (C) (E + C, n = 50; E, n = 49). The dose of E was 560 mg and that of C 3.2 g for the first month, thereafter 1.6 g. We saw elevated ICTP and PICP levels in the majority of the patients. A transient decrease in ICTP values occurred simultaneously with pain relief. The changes were more accentuated in the E + C than in the E group but the difference was not significant. In each group serum phosphate concentration decreased markedly (P = 0.001) whereas the activity of alkaline phosphatase remained increased, both indicating a development of osteomalacia during E therapy. The short-term antiosteoclastic effect of C may be explained by the dose reduction, hyperosteoidosis and osteomalacia which inhibit the binding of C on the crystal surfaces and by the late phase of disease.

Administration, Oral↗