Search PubMed⌕ Search

Biomedical subjects

J Risteli

Publications and source records attributed to J Risteli.

At least 217 records · Page 12Linked to original sources

Radioimmunoassay of the carboxyterminal propeptide of human type I procollagen.

Type I collagen is the most abundant collagen type in soft tissues and the only type found in mineralized bone. We established a rapid equilibrium radioimmunoassay for the carboxyterminal propeptide of human type I procollagen (PICP), to be used as an indicator of the synthesis of type I collagen. We isolated type I procollagen from the medium of primary cultures of human skin fibroblasts, digested the protein with highly purified bacterial collagenase, and purified PICP by lectin-affinity chromatography, gel filtration, and ion-exchange separation on HPLC. The purity of the protein was verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by N-terminal amino acid sequencing of its component chains. The final radioimmunoassay was established with polyclonal rabbit antibodies. Material antigenically related to PICP is readily detected in human serum. There is only one form of the serum antigen, its molecular size and affinity to the antibodies being similar to those of the isolated propeptide. Intra- and interassay CVs are 3% and 5%, respectively. Preliminary reference intervals for healthy adults (18 to 61 years of age) are 38-202 micrograms/L for men and 50-170 micrograms/L for women: in men the concentration is inversely related to age. The serum antigen is stable during storage and after repeated thawing.

Adolescent↗

Amino-terminal propeptide of type III procollagen: a new prognosis indicator in human ovarian cancer.

To investigate the clinical usefulness of the amino-terminal propeptide of type III procollagen (PIIINP) as an indicator of ovarian cancer behavior, 30 patients with advanced epithelial malignancy were monitored with serial serum PIIINP and CA-125 determinations before and during treatment. Initially, PIIINP and CA-125 concentrations were each separately increased in 87% of the cases and, simultaneously, in 77% of the cases. In monitoring treatment responses, PIIINP and CA-125 were identical in 17 patients (57%), both being good predictors of the clinical behavior of the disease in 16 cases and poor predictors in one case. In 13 patients (43%) they were complementary to each other. In three cases PIIINP alone and in one case CA-125 alone were clinically useful prognosis indicators. During the period of complete clinical response to cytotoxic chemotherapy of 16 patients, the CA-125 concentrations decreased to normal before the clinical disappearance of the tumor in eight cases. PIIINP did so in only two cases, thus correlating more precisely with the presence of malignancy. In second-look laparotomies, PIIINP concentrations correlated with the presence of occult cancer better than those of CA-125. In predicting recurrent malignancy in patients with transient complete response, PIIINP and CA-125 were clinically equal. According to the present data, PIIINP concentrations often give information not obtainable by CA-125, thus being useful in monitoring the clinical behavior of ovarian cancer.

Adult↗

Growth velocity, growth hormone therapy, and serum concentrations of the amino-terminal propeptide of type III procollagen.

The relationship between serum concentrations of the amino-terminal propeptide of type III procollagen (PIIINP) and growth was assessed in 307 healthy subjects and 82 children with disorders of growth (41 with insufficient growth hormone, 23 with short stature and normal endocrinologic studies, 18 with tall stature) by means of a recently developed, simplified PIIINP radioimmunoassay. The PIIINP value appeared to be related to height velocity; in healthy children of each sex, the pattern of change with age mirrored the shape of the standard height velocity curve; in children with disorders of growth, there was a statistical correlation (p less than 0.001) between PIIINP concentration and height velocity. However, measurement of serum PIIINP alone had no diagnostic value because there was considerable overlap of PIIINP values in children with growth hormone insufficiency, short stature, normal stature, and tall stature. The most appropriate application of PIIINP may be in the monitoring of prepubertal children receiving exogenous growth hormone therapy; in these patients, increases in height velocity were reflected by increases in PIIINP, and early increases in PIIINP may have predictive value.

Body Height↗

The O75X adhesin of uropathogenic Escherichia coli is a type IV collagen-binding protein.

Interaction of the basement-membrane binding O75X adhesin of uropathogenic Escherichia coli with various extracellular matrix proteins was studied. The adhesin showed strong binding to type IV collagen immobilized on microtitre plates, whereas other collagens, laminin and fibronectin, were only weakly recognized. Similarly, specific binding of [125I]-labelled type IV collagen to O75X-positive bacteria was shown. Interaction of the two proteins was also demonstrated by affinity chromatography of the O75X adhesin on immobilized type IV collagen. The adhesin bound strongly to the immobilized N-terminal 7S domain of type IV collagen, and the binding of [125I]-labelled type IV collagen to O75X-positive bacteria was inhibited by the soluble 7S domain. Binding of O75X to type IV collagen and to its 7S domain was specifically inhibited by chloramphenicol but was not affected by periodate or endoglycosidase-H treatment of the glycoproteins. Our results show that the 7S domain of type IV collagen is the basement membrane receptor for the O75X adhesin and suggest an interaction based on protein-protein recognition. Inhibition of the interaction by chloramphenicol favours the supposition that a modified tyrosine is involved in the binding site.

Acetylglucosaminidase↗

Malotilate prevents accumulation of type III pN-collagen, type IV collagen, and laminin in carbon tetrachloride-induced pulmonary fibrosis in rats.

Orally administered malotilate was studied as a protective antifibrotic agent with respect to experimentally induced pulmonary fibrosis in rats using immunohistochemical methods. Specific antibodies raised in rabbits against the aminoterminal propeptide of human type III procollagen and against two basement membrane proteins, the 7S domain of human type IV collagen and the P1 fragment of human laminin, were used for the immunohistochemical analysis, and the result was confirmed by morphometry. Intraperitoneally injected carbon tetrachloride significantly increased the volume densities of reticulin fibers, type III pN-collagen, type IV collagen, and laminin, whereas treatment with malotilate completely normalized these. Binding of the antibodies to rat antigens was also demonstrated by immunoelectron microscopy in which the collagen fibers with a typical periodic pattern were labeled positively with rabbit antitype III procollagen, whereas the amorphous basement membrane material reacted positively with rabbit antitype IV collagen and antilaminin, indicating good, specific cross-reactivity between these antibodies and the rat antigens. It is concluded that malotilate prevents the accumulation of type III pN-collagen and two basement membrane proteins, type IV collagen and laminin, in experimental pulmonary fibrosis, and can potentially be developed to provide a useful drug for preventing pulmonary fibrosis in humans.

Animals↗

Immunoelectron microscopic localization of laminin, type IV collagen, and type III pN-collagen in reticular fibers of human lymph nodes.

We studied the ultrastructural distribution of laminin, type IV collagen, and the amino terminal pro-peptide of type III collagen (type III pN-collagen) in normal human lymph nodes. After fixation with freshly prepared 4% paraformaldehyde mixed with 0.1% glutaraldehyde, cryoultramicrotomy proved to preserve the antigenicity of these proteins better than embedding in Lowicryl K4M. Sections were treated with rabbit antibodies against the 7S domain of human type IV collagen, the fragment P1 of human laminin, and the amino terminal pro-peptide of human type III pro-collagen, followed by anti-rabbit IgG conjugated to 10-nm colloidal gold. Laminin and type IV collagen were seen in the basement membrane structures of the blood vessels and in the walls of sinuses. The amorphous material between the collagenous fibers in locations corresponding to reticular fibers also contained laminin and type IV collagen. The amino terminal pro-peptide of type III pro-collagen was present in the collagenous fibers in reticular fibers and in the walls of blood vessels and sinuses. Therefore, a significant number of the type III collagen molecules in these fibers must have retained their amino terminal pro-peptide. These results indicate that the basement membrane proteins laminin and type IV collagen are genuine components of reticular fibers, as suggested earlier by immunohistochemical studies at the light microscopic level.

Basement Membrane↗

Aminoterminal propeptide of type-III procollagen in serum--an indicator of clinical behavior of advanced ovarian carcinoma?

In ovarian carcinoma, elevated serum concentrations of the aminoterminal propeptide of type-III procollagen are related to the clinical stage of the disease and to the presence of ascites, which contains very high concentrations of the propeptide. In a follow-up of patients with advanced disease, favorable clinical course was associated with normalizing propeptide values, whereas in progressing disease the values increased several weeks before clinical progression. In stable disease the concentrations were constantly above the reference range. Laminin and type-IV-collagen-related serum antigens were mostly within the reference range.

Adult↗

Serum basement membrane and type III procollagen-related antigens in primary biliary cirrhosis.

A characteristic histological lesion in early primary biliary cirrhosis (PBC) is disruption of the basement membrane around small bile ducts, which at later stages of the disease is followed by fibrosis. To assess the significance of serum basement membrane- and type III procollagen-related antigens in reflecting such processes, we have measured radioimmunologically the concentrations of serum laminin, type IV collagen and the aminoterminal propeptide of type III procollagen in 22 patients with PBC, classified into four stages according to liver histology. The mean laminin concentration in PBC patients was twice that of the healthy control subjects. Increased concentrations were observed in all patients with stage III or IV of the disease and also in 60% (6/10) of the patients, with early stages (I or II). Elevated serum type IV collagen concentrations were found only in four patients, all in the late, fibrotic stages of the disease. The basement membrane protein changes in serum were in accordance with immunohistochemical findings obtained with the antibodies against these proteins. Neither of these serum parameters emerged, however, as a significant predictive factor for survival. The changes in serum aminoterminal propeptide of type III procollagen resembled those in laminin P1. Moreover, the propeptide was also significant as a predictive factor for survival.

Adult↗

Type IV collagen and laminin in slow and fast skeletal muscle in rats--effects of age and life-time endurance training.

The changes in the biochemical composition of basement membrane (BM) in slow-twitch (m. soleus, MS) and fast-twitch (m. rectus femoris, MRF) skeletal muscles of rats were studied during aging and life-time endurance training (treadmill running). The concentrations of the 7S domain of type IV collagen and of the P2 fragment of laminin were determined with radioimmunoassays in the muscles of rats aged 1, 2, 4, 10, and 24 months. The concentration of type IV collagen was higher in MS than in MRF and increased significantly with age. At older ages, the concentration tended to be higher in the MS of trained than untrained rats. The concentration of laminin was significantly higher in MRF than in MS, especially in old age. Consequently, the ratio of type IV collagen to laminin was significantly higher in MS than in MRF, the difference increasing with advancing age. The results show that the BMs in slow muscle are much more collagenous than those in fast muscle which contains, on the contrary, a higher concentration of laminin. This difference seems only partly to be explained by the higher capillarization of slow twitch muscle fibers. Aging and training seem further to distinguish the composition of the BM in slow and fast muscle.

Aging↗

Aminoterminal propeptide of type III procollagen in methotrexate-induced liver fibrosis and cirrhosis.

Twenty-four psoriatic patients on methotrexate were studied with liver biopsies and serum measurements of aminoterminal propeptide of type III procollagen (PIII NP). All but one of nine patients with serum levels of PIII NP above the normal range had liver fibrosis or cirrhosis and no normal liver biopsies were obtained in this group. In contrast, nine normal liver biopsies and two biopsies with minimal fibrosis were found among the 15 patients with normal serum levels of PIII NP. The study indicates that aminoterminal propeptide of type III procollagen can be utilized as a valuable non-invasive marker of fibrogenesis in the liver. This analysis is not specific for the liver, but it seems that the number of liver biopsies probably can be reduced in psoriatics on methotrexate who have normal levels of PIII NP.

Adult↗

Serum aminoterminal propeptide of type III procollagen: a potential predictor of the response to growth hormone therapy.

The circulating concentrations of insulin-like growth factor I (IGF-I) and immunoreactive aminoterminal propeptide of type III procollagen (PIIINP) were measured in 12 children with short stature (8 GH deficient and 4 non-GH deficient) before and after 1 week, 5 weeks, and 3, 6, and 12 months of treatment with biosynthetic hGH. Seven children had a growth response (increase in relative growth velocity greater than 1.5 SD during the initial 6 months) to GH therapy (responders), whereas 5 failed to respond (nonresponders). No relationship was found between the pretreatment plasma IGF-I levels or their changes during therapy and the growth response. Serum PIIINP levels increased considerably in all but 3 children, after as little as 1 week of GH administration. After 5 weeks, all responders had an increase in their serum PIIINP concentrations of 40% or more, whereas the nonresponders had less or no increments. There was a close correlation between the GH-induced increase in serum PIIINP levels at 5 weeks and growth velocity after 6 months of GH therapy (r = 0.77; P less than 0.01). The correlation was even stronger with the growth velocity at 12 months (r = 0.83; P less than 0.001). The serum PIIINP response to short-term GH administration could be an early predictor of the growth response to long-term GH therapy. In contrast to plasma IGF-I, the PIIINP response may be useful both in GH deficient and non-GH deficient children.

Adolescent↗

The aminoterminal propeptide of type III procollagen and basement membrane components in serum during wound healing in man.

The aim of this study was to investigate if the serum concentrations of antigens related to basement membrane components and to the interstitial type III collagen reflect the sequential and transitional synthesis of basement membranes and of type III collagen in wound granulation tissue. The aminoterminal propeptide of type III collagen, the 7S domain of type IV collagen and the P1 fragment of laminin were determined in 11, 10 and 6 patients, respectively, during wound healing following intraabdominal surgery. No change was observed in the type III propeptide level at the first postoperative day. During further follow-up (mean 71 days, range 21-155 days), the propeptide levels showed a transitional increase, with a maximum at day 10. A sequential pattern was observed in the increase of the serum concentrations, as the maximum increase of the basement related antigens in serum occurred within the first 7 postoperative days. This is in accordance with observations of an early formation of basement membranes in blood vessels, preceding deposition of interstitial collagens in granulation tissue. The results support the assumption that the serum concentrations of connective tissue related antigens may be valuable markers of wound healing in man.

Adult↗

Rapid equilibrium radioimmunoassay for the amino-terminal propeptide of human type III procollagen.

This is an equilibrium-type radioimmunoassay for the amino-terminal propeptide of type III procollagen (PIIINP), which overcomes the problem of nonparallelism between the standard and human serum samples encountered with earlier assays. Proper selection of antiserum and reaction conditions diminishes interference from degradation products of the propeptide in serum. Because a rapid solid-phase-bound second-antibody step is included, the assay takes only 3 h. The intra-assay and the interassay CVs are both about 5%. In infants and children the concentration of PIIINP in serum closely parallels the growth-velocity curve. For 88 presumably healthy adults, the PIIINP concentration was 1.7-4.2 micrograms/L, about a third that measured with the previously available commercial assay. This is because of lack of inhibition by small Col 1 domain-related degradation products.

Adolescent↗

The response evaluation of bone metastases in mammary carcinoma. The value of radiology, scintigraphy, and biochemical markers of bone metabolism.

The correlation between response of metastatic bone lysis and bone pain, various biochemical markers of bone metabolism, and radiological and scintigraphic findings was investigated in 49 women with breast cancer included in a calcitonin supportive therapy trial. All patients had dominant skeletal disease and were on stable systemic treatment (cytotoxic or hormonal) for a least 6 months before the first response evaluation. Bone pain correlated poorly with treatment response. Changes in sclerotic metastases did not show any apparent relation to changes in lytic lesions. A correlation between bone scans and lytic activity on radiographs was found. The absolute level of biochemical bone markers did not correlate with treatment response, but seemed instead to reflect the rate of bone turnover. The relative level of bone markers with respect to baseline showed better correlation to treatment response. The best conventional marker of disease activity was urinary hydroxyproline/creatinine. Propeptide of Type III procollagen (PIIINP), a novel marker reflecting collagen turnover, promises to be at least as sensitive as hydroxyproline. Stable and regressing patients had the same prognosis and significantly longer survival than progressors.

Biomarkers, Tumor↗

Aminoterminal propeptide of type III procollagen in healing wound in humans.

For quantitative analysis of wound healing in surgical patients, samples of wound fluid were collected through a silicone rubber tube and their concentration of the aminoterminal propeptide of type III procollagen was measured with a specific radioimmunoassay. Peritoneal fluid, collected through an abdominal drain, and serum were also analyzed. At day 1 after operation, the mean concentration of the propeptide was 30 times higher than the mean preoperative serum level (2.5 micrograms/L). A significant increase (p less than 0.001) occurred at day 3 in the wound and at day 2 in peritoneal fluid. At day 5 the mean wound concentration (2670 micrograms/L) was 1000 times higher than the serum level. In serum a small but significant increase (p less than 0.05) was found at days 5 and 30. The increase in wound fluid resulted from the intact, liberated propeptide, indicating that the results reflect the synthesis of type III collagen deposited in the wound. This procedure offers a quantitative tool for wound healing studies. Other extracellular matrix components can also be measured, the sequential pattern of their appearance can thus be assessed, and disturbances and treatment effects in wound healing can be detected.

Adult↗

Collagen metabolism in normal and complicated pregnancy: changes in the aminoterminal propeptide of type III procollagen in serum.

The turnover of type III collagen, a major constituent of the myometrium and the uterine cervix, during pregnancy was evaluated by monitoring serum antigens related to the aminoterminal propeptide of type III procollagen. Their concentration increased markedly towards term in most uncomplicated pregnancies, while their size distribution throughout the pregnancy resembled that seen in the sera of normal healthy persons. In some patients, however, the level remained low, indicating interindividual variation in the release into serum and metabolism of the propeptide. There were no distinct changes during or immediately after vaginal delivery. Values exceeding the reference range for uncomplicated pregnancies were found during weeks 28-37 in patients with pre-eclampsia, essential hypertension, intrahepatic cholestasis of pregnancy or twin pregnancy. Thus, pregnancy should be taken into account when evaluating results of the serum assay for the aminopropeptide and the use of this assay as an indicator of pregnancy complications warrants further study.

Cholestasis↗